Heidi Splete

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Patients with infected pancreatic necrosis (IPN) are more likely to experience organ failure and mortality, which makes identifying them as quickly as possible especially crucial. A new study aimed to make this task a bit easier by categorizing the main risk factors for IPN in a cohort of patients with severe acute pancreatitis, which included extensive spread of necrotic collections, preceding bacteremia, and preceding open abdomen treatment, as well as postinterventional pancreatitis.

In their study, published in the Journal of Gastrointestinal Surgery, Henrik L. Husu, MD, of the University of Helsinki, and colleagues noted the inherent challenges of rendering a preoperative diagnosis of IPN.

“Fever and increasing inflammation markers may indicate suspicion of IPN, but these are very common in patients with severe acute pancreatitis treated in the ICU,” and more knowledge of specific IPN risk factors is needed to improve clinical decision-making, they said.

Dr. Husu and colleagues identified 163 adults with acute pancreatitis admitted to the ICU at a single center between 2010 and 2018, approximately 68% of whom had alcoholic necrotizing pancreatitis. Pneumonia, bacteremia, and IPN occurred at an average of 4, 16, and 23 days, respectively, after ICU admission.

Forty-seven patients (28.8%) developed IPN within 90 days of ICU admission, all patients had a least one persistent organ failure, and 60% had multiple organ failure within 24 hours of ICU admission.

In a multivariate regression analysis, independent risk factors for IPN included postoperative or postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (odds ratio,13.5) and widespread necrotic collections (OR, 5.7 for unilateral paracolic or retromesenteric; OR, 21.8 for bilateral paracolic or unilateral paracolic and retromesenteric). Other risk factors were preceding bacteremia (OR, 4.8) and preceding open abdomen treatment for abdominal compartment syndrome (OR, 3.6).

After 90 days, 29 patients had died, including 7 with IPN and 22 without IPN. In addition, patients with IPN had longer overall hospital stays and ICU stays, higher rates of ICU readmission, and greater use of open necrosectomy, the researchers noted.

The study findings were limited by several factors, including the retrospective design, lack of controls, potential differences in treatment protocols, and the survival bias that prevented direct comparison of mortality in patients with and without IPN, the researchers noted. “This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself.”

However, the researchers noted that “the strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course,” and results indicate a significant morbid outcome associated with IPN. “In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential,” they emphasized. 
 

More data may prompt greater intervention

“IPN portends a poor prognosis, and can be challenging to both diagnose and treat,” Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, said in an interview. “Identifying risk factors for development of IPN may facilitate earlier therapy that could modify the natural history of this disease.”

Dr. Ketwaroo said he was not surprised by the study findings. “This was a small single-center, retrospective study, where infection could only be ascertained among those who received interventions, and the findings should thus be interpreted within these limitations. Overall, however, I was not surprised. More extensive necrosis and opportunities for infectious seeding of necrosis such as interventions (ERCP) and bacteremia would be expected risk factors. I was surprised by the use of prophylactic antibiotics, as well as the high rate of open necrosectomy, though this should not affect the main findings of risk factors for infection.

“The studies highlight that a significant portion of patients with severe acute pancreatitis with necrosis will develop infection,” said Dr. Ketwaroo. “Being aware of the risk factors for infection, as identified in this study, can add to our clinical judgment in suspecting infection and opting for debridement. Especially with advancements in endoscopic necrosectomy, gastroenterologists may be more inclined to intervene when suspecting IPN. The next steps for research are to validate risk factors in larger, prospective studies.”

The study was supported by governmental competitive funds for medical research, a research grant from the Medical Society of Finland, and a research grant from Perkléns Foundation. The researchers had no financial conflicts to disclose. Dr. Ketwaroo had no financial conflicts to disclose but is a member of the GI & Hepatology News editorial advisory board.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Different kinds of neuropsychiatric (NP) events in patients with systemic lupus erythematosus (SLE) have substantial variability in their occurrence, resolution, and recurrence over time, as well as in their predictors, according to new research from a large, prospective, international, inception cohort study.

Because “multiple NP events due to different causes may present concurrently in individual patients, the findings emphasize the importance of recognizing attribution of NP events as a determinant of clinical outcome,” John G. Hanly, MD, of Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., and colleagues wrote in Arthritis & Rheumatology.

In a previous study of the same group of 1,827 patients with SLE, NP events occurred in about half and approximately one-third of these events were deemed disease related. They also “occurred most frequently around the diagnosis of SLE and had a significant negative impact on health-related quality of life,” the researchers wrote.

Researchers involved with the Systemic Lupus International Collaborating Clinics recruited the 1,827 adults with SLE over an 11-year period during 1999-2011 from a total of 31 sites in Europe, Asia, and North America. The average age of the patients at study enrollment was 35 years, 89% were women, and 49% were White. The mean disease duration was 5.6 months, and 70% of patients were taking corticosteroids at enrollment.

Over an average follow-up period of 7.6 years, 955 patients (52.3%) experienced a single neuropsychiatric event, and 493 (27.0%) experienced two or more events; the total number of unique NP events was 1,910. Most of these unique events (92%) involved the central nervous system, and 8.4% involved the peripheral nervous system.

The researchers used multistate models to attribute NP events to SLE based on factors that included the temporal onset of NP events in relation to SLE diagnosis, concurrent non-SLE factors, and NP events that are common in healthy controls. The four states in the multistate models were no NP events, no current NP event but a history of at least one event, new or ongoing NP events, and death. The results included a multivariate analysis of a model involving 492 observed transitions into new or ongoing NP events.

In the multivariate analysis, factors positively associated with SLE-attributed NP events included male sex (hazard ratio, 1.35; P = .028), concurrent non-SLE NP events excluding headache (HR, 1.83; P < .001), active SLE based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (HR, 1.19; P = .012), and corticosteroid use (HR, 1.59; P = .008). The researchers also found that SLE-attributed NP events were negatively associated with Asian race/ethnicity, postsecondary education, and use of immunosuppressive drugs.

Another multivariate analysis found that non-SLE NP events were positively associated with only concurrent SLE-attributed NP events excluding headache (HR, 2.31; P < .001), but negative associations were seen with non-U.S. African race/ethnicity and Asian race/ethnicity.

The researchers found that SLE-attributed NP events had higher rates of resolution, compared with non-SLE NP events, with the exception of headache, which had similar resolution for both event groups.

“Resolution of SLE events was more likely in patients with Asian race/ethnicity and those with Central/Focal nervous system disease with no effect seen for age at diagnosis,” the researchers noted. “For non-SLE NP events, African race/ethnicity at non-U.S. sites and younger age at diagnosis was associated with a better outcome.”

The study findings were limited by several factors including the predominantly White patient population and the clustering of NP events into limited categories, which may have reduced the identification of more specific associations, the researchers noted. Also, the assessment of NP event outcomes did not include patient perceptions, and the relatively short follow-up period does not allow for assessment of later NP events such as cerebrovascular disease. However, “despite these limitations the current study provides valuable data on the presentation, outcome and predictors of NP disease in SLE patients enrolled in a long-term, international, disease inception cohort,” the researchers concluded.

The study received no outside funding. Dr. Hanly was supported by a grant from the Canadian Institutes of Health Research but had no financial conflicts to disclose. Several coauthors received grant support from various institutions, but not from industry, and had no financial conflicts to disclose.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Healthy first-degree relatives of individuals with HLA-B27–positive axial spondyloarthritis who also were HLA-B27 positive were at increased risk for developing the disease themselves within 1 year, based on data from an ongoing prospective cohort study that involved 202 first-degree relatives.

Axial spondyloarthritis (axSpA) generally arises between ages 18 and 40 years, but diagnosis can be delayed, in part because of the lack of biomarkers and nonspecific symptoms, wrote Henriëtte M.Y. de Jong, MD, PhD, of the University of Amsterdam, and colleagues.

Individuals who carry the HLA-B27 gene are predisposed to axSpA, and their first-degree relatives (FDRs) are at increased risk as well, the researchers said. Therefore, “studying [FDRs] could help to identify clinical signs, imaging abnormalities, and biomarkers that are predictive of development of axSpA,” they said.

In a study published in Arthritis Care & Research, the investigators reviewed data from patients in the Pre-SpA cohort, a 5-year prospective study of healthy-seeming FDRs of patients with HLA-B27–positive axSpA. The researchers previously reported that up to one-third of 51 FDRs had clinical features associated with SpA at baseline, despite the lack of a diagnosis.

The current study included an additional 151 FDRs who had answered yearly questions about back pain and undergone a yearly physical exam and plain radiographs and MRI imaging at baseline.

Overall, 65% reported back pain at baseline and 19% met criteria for inflammatory back pain, with a median visual analog score (VAS) for back pain of 22. No active arthritis was noted, but 5 FDRs reported a past arthritis diagnosis, 48 reported arthralgia, and 16 had at least one tender joint on physical exam. Eight FDRs had past diagnoses of enthesitis, and one had a history of dactylitis.

In assessing disease activity, the researchers found an elevated C-reactive protein (CRP) level in 24 FDRs and 11 had an elevated erythrocyte sedimentation rate (ESR).

On MRI of the sacroiliac joint at baseline, 10% of the FDRs had SPARCC (Spondyloarthritis Research Consortium of Canada) scores of 2 or higher, 4% had scores of 5 or higher, and 4% had deep lesions.

A total of 123 FDRs had complete data at a 1-year follow-up visit.

“All features were equally distributed between HLA-B27–positive and –negative FDRs,” the researchers noted. However, at the end of the 1-year follow-up period, seven (6%) of the FDRs were clinically diagnosed with axSpA, and six of them were HLA-B27 positive. Disease activity measures had increased at 1 year in all seven patients with newly diagnosed axSpA.

The study findings were limited by several factors, including the possible channeling of FDRs with current complaints of back pain into the study and the inability to confirm details of family and medical history, the researchers noted. However, the VAS back pain scores reported by the FDRs suggest that this pain was not a fixture in daily life, they wrote.

The results confirm the prevalent subclinical signs of SpA in healthy FDRs of patients with axSpA who were positive and negative for HLA-B27, but also confirm that clinical progression occurred primarily in the HLA-B27–positive patients in conjunction with inflammatory back pain, the researchers said.

“Further follow-up of the Pre-SpA cohort will give more robust insight into the characteristics of FDRs that progress towards clinical SpA, thereby hopefully enabling the characterization of high-risk FDRs,” they concluded.

The Pre-SpA cohort is supported by the Dutch Arthritis Society. Lead author Dr. de Jong had no financial conflicts to disclose. One coauthor is employed by UCB, and several others disclosed relationships with AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

The Food and Drug Administration has expanded the approval of secnidazole to include treatment of trichomoniasis in adults, according to a statement from manufacturer Lupin Pharmaceuticals.

Trichomoniasis vaginalis is a common, nonviral, curable sexually transmitted disease that affects approximately 3 million to 5 million adults in the United States each year; the infection can linger for months or years if left untreated, and may have a negative impact on reproductive health. The drug was approved for the treatment of bacterial vaginosis in 2017.

The availability of a single-dose oral treatment for both trichomoniasis and bacterial vaginosis may help improve adherence and reduce risk factors associated with these conditions, including pelvic inflammatory disease and other sexually transmitted infections, according to the statement.

The approval for the new indication was based primarily on data from a phase 3 clinical trial in which women with a confirmed trichomoniasis diagnosis were randomized to a single dose of 2 g oral secnidazole or a placebo. Secnidazole showed a 92.2% cure rate for patients with trichomoniasis, compared with placebo, based on cultures collected 6-12 days after dosing. Cure rates in subsets of patients with HIV and bacterial vaginosis were 100% and 95%, respectively.

The most common treatment-related adverse events were vulvovaginal candidiasis and nausea, each reported in 2.7% of study participants. The study findings were published in March 2021 in Clinical Infections Diseases.

Secnidazole also is approved for treatment of trichomoniasis in men, based on data from four open-label studies, one with men only and three including both men and women, according to the statement.

Full prescribing information for secnidazole is available here.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

A novel oral inhibitor of transglutaminase 2 appears to block gluten-induced mucosal damage in patients with celiac disease at three different doses, based on proof-of-concept trial data from 132 patients.

“Currently, no drug therapy reliably prevents the effects of dietary gluten or has been approved by regulators to treat celiac disease,” which remains an unmet need in these patients, many of whom struggle with symptoms even when they adhere to a gluten-free diet, wrote Detlef Schuppan, MD, of Johannes Gutenberg University of Mainz (Germany) and colleagues.

Celiac disease is driven in part by the enzyme transglutaminase 2, and a transglutaminase 2 inhibitor known as ZED1227 has been tested safely in phase 1 trials, they reported.

“ZED1227 targets the intestinal mucosa predominantly and thereby mediates protection; thus, it is unaffected by the complexity of the food matrix and is less dependent on the timing of ingestion of gluten-containing food,” the researchers explained.

In a study published in the New England Journal of Medicine, the researchers assessed the safety and efficacy of three dose levels of ZED1227. Adults with controlled celiac disease were randomized to doses of 10 mg (41 patients), 50 mg (41 patients), and 100 mg (41 patients), and 40 patients received a placebo. Of these, 35, 39, 28, and 30 patients, respectively, had sufficient duodenal biopsy samples for analysis.

Patients underwent a daily gluten challenge of 3 g for 6 weeks. At the end of 6 weeks, the primary study endpoint of attenuation of gluten-induced mucosal damage was measured by the ratio of villus height to crypt depth.

Patients in all three treatment groups showed significant attenuation of mucosal damage. The change in the average ratio of villus height to crypt depth compared to placebo in the 10-mg, 50-mg, and 100-mg groups was 0.44, 0.49, and 0.48, respectively, with P values equal to .001 in the 10-mg group and less than .001 in the 50-mg and 100-mg groups.

Adverse events were similar across all treatment groups and the placebo group, with the exception of a rash in three patients in the 100-mg group. A total of 74 patients reported adverse events, and the most common were headache, nausea, diarrhea, vomiting, and abdominal pain. The investigators determined that from 34% to 55% of the adverse events across groups were related to the study drug or placebo.

Two patients developed serious adverse events that were deemed related to the study drug or placebo; one patient in the 50-mg group developed migraine with aura, and one placebo patient developed ventricular extrasystoles. The patients recovered after discontinuing the drug or placebo.

Secondary endpoints included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score. Estimated changes in intraepithelial lymphocyte density, compared with placebo, were –2.7 cells per 100 epithelial cells in the 10-mg group, −4.2 cells per 100 epithelial cells in the 50-mg group, and −9.6 cells per 100 epithelial cells in the 100-mg group. Compared with those of patients taking placebo, the 6-week changes in Celiac Symptom Index scores and Celiac Disease Questionnaire scores suggested slight improvements in symptoms and quality of life for the 100-mg dose.

The study findings were limited by several factors including missing data and loss of several patients to follow-up, as well as the short trial duration and use of controlled gluten ingestion, the researchers noted. Larger studies involving real-world conditions of minor gluten ingestion are needed to support the preliminary signs of safety and efficacy, they said.

Study strengths include high levels of patient adherence to the treatment and the gluten challenge, they said. “Future studies of ZED1227 in more patients are needed to provide additional evidence of the safety and efficacy of the drug, potentially in real-life conditions with minor gluten ingestion,” they concluded.
 

Translating potential into practice

“An absence of mucosal damage is a critical criterion to ensure the long-term health of a patient, and this clinical trial in celiac disease meets this important endpoint,” Bana Jabri, MD, of the University of Chicago, wrote in an accompanying editorial.

The primary endpoint of no mucosal damage is “especially notable because it was achieved under a controlled gluten challenge, albeit with a relatively moderate amount of gluten (a regular diet contains 12 g of gluten daily, whereas the challenge involved 3 g daily) and for a short period of time,” Dr. Jabri said. The reduction of disease-associated symptoms and apparent improvement in quality of life with 100-mg dose added value to the findings, she said.

Future research areas include whether cross-reactive T cells, which were not analyzed in the current study, might “expand and become pathogenic after a long-term gluten challenge,” Dr. Jabri noted.

However, “ZED1227 is the first nondietary treatment that has preliminarily shown the capacity to prevent mucosal damage in persons with celiac disease,” she said.

“Although this trial is very encouraging, whether treatment with ZED1227, and more generally transglutaminase 2 inhibition, in patients with celiac disease will be efficient in real life and during long-term gluten exposure remains to be determined,” Dr. Jabri concluded.
 

Need for data on dosing consistency

“Celiac disease affects up to 2% of the population in many countries, and the main therapy of celiac disease is avoidance of gluten,” Kim Isaacs, MD, of the University of North Carolina, Chapel Hill, said in an interview. “This is challenging due to the ubiquitous nature of gluten in many food products,” she said. “Restrictive eating also affects social interaction which is often focused around food,” she added. “Availability of an oral therapy that is effective to treat celiac in the face of gluten exposure will have a profound impact on patients in terms of liberalization of dietary intake.”

Overall, “the changes in the villus height to crypt depth was similar between all the active treatment groups, whereas there was a dose-dependent reduction in transepithelial lymphocyte density,” Dr. Isaacs noted. “The symptom improvement was greatest in the 100-mg group, suggesting that symptoms may be related to a greater extent to the lymphocyte density than the minimal differences in villus height to crypt depth ratios seen in the active treatment groups,” she said.

Potential barriers to the use of the treatment include cost because “this will need to be a daily long-term therapy,” said Dr. Isaacs. “Compliance is a potential barrier as well,” she said. “This study looks at daily administration of the transglutaminase 2 inhibitor and shows a benefit, but it is not clear whether missing doses of the medication will have a prolonged impact on efficacy,” she emphasized. Consequently, long-term efficacy studies are needed, Dr. Isaacs said. Other research questions to answer include whether patients will become refractory to the beneficial effects over time, the effect of missing doses, and whether patients would lose all the benefits of the therapy if dosing is not consistent, she emphasized.

The study was funded by Dr. Falk Pharma. The researchers, as well as Dr. Jabri and Dr. Isaacs, had no financial conflicts to disclose. Dr. Isaacs is on the editorial advisory board of GI & Hepatology News.

A novel oral inhibitor of transglutaminase 2 appears to block gluten-induced mucosal damage in patients with celiac disease at three different doses, based on proof-of-concept trial data from 132 patients.

“Currently, no drug therapy reliably prevents the effects of dietary gluten or has been approved by regulators to treat celiac disease,” which remains an unmet need in these patients, many of whom struggle with symptoms even when they adhere to a gluten-free diet, wrote Detlef Schuppan, MD, of Johannes Gutenberg University of Mainz (Germany) and colleagues.

Celiac disease is driven in part by the enzyme transglutaminase 2, and a transglutaminase 2 inhibitor known as ZED1227 has been tested safely in phase 1 trials, they reported.

“ZED1227 targets the intestinal mucosa predominantly and thereby mediates protection; thus, it is unaffected by the complexity of the food matrix and is less dependent on the timing of ingestion of gluten-containing food,” the researchers explained.

In a study published in the New England Journal of Medicine, the researchers assessed the safety and efficacy of three dose levels of ZED1227. Adults with controlled celiac disease were randomized to doses of 10 mg (41 patients), 50 mg (41 patients), and 100 mg (41 patients), and 40 patients received a placebo. Of these, 35, 39, 28, and 30 patients, respectively, had sufficient duodenal biopsy samples for analysis.

Patients underwent a daily gluten challenge of 3 g for 6 weeks. At the end of 6 weeks, the primary study endpoint of attenuation of gluten-induced mucosal damage was measured by the ratio of villus height to crypt depth.

Patients in all three treatment groups showed significant attenuation of mucosal damage. The change in the average ratio of villus height to crypt depth compared to placebo in the 10-mg, 50-mg, and 100-mg groups was 0.44, 0.49, and 0.48, respectively, with P values equal to .001 in the 10-mg group and less than .001 in the 50-mg and 100-mg groups.

Adverse events were similar across all treatment groups and the placebo group, with the exception of a rash in three patients in the 100-mg group. A total of 74 patients reported adverse events, and the most common were headache, nausea, diarrhea, vomiting, and abdominal pain. The investigators determined that from 34% to 55% of the adverse events across groups were related to the study drug or placebo.

Two patients developed serious adverse events that were deemed related to the study drug or placebo; one patient in the 50-mg group developed migraine with aura, and one placebo patient developed ventricular extrasystoles. The patients recovered after discontinuing the drug or placebo.

Secondary endpoints included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score. Estimated changes in intraepithelial lymphocyte density, compared with placebo, were –2.7 cells per 100 epithelial cells in the 10-mg group, −4.2 cells per 100 epithelial cells in the 50-mg group, and −9.6 cells per 100 epithelial cells in the 100-mg group. Compared with those of patients taking placebo, the 6-week changes in Celiac Symptom Index scores and Celiac Disease Questionnaire scores suggested slight improvements in symptoms and quality of life for the 100-mg dose.

The study findings were limited by several factors including missing data and loss of several patients to follow-up, as well as the short trial duration and use of controlled gluten ingestion, the researchers noted. Larger studies involving real-world conditions of minor gluten ingestion are needed to support the preliminary signs of safety and efficacy, they said.

Study strengths include high levels of patient adherence to the treatment and the gluten challenge, they said. “Future studies of ZED1227 in more patients are needed to provide additional evidence of the safety and efficacy of the drug, potentially in real-life conditions with minor gluten ingestion,” they concluded.
 

Translating potential into practice

“An absence of mucosal damage is a critical criterion to ensure the long-term health of a patient, and this clinical trial in celiac disease meets this important endpoint,” Bana Jabri, MD, of the University of Chicago, wrote in an accompanying editorial.

The primary endpoint of no mucosal damage is “especially notable because it was achieved under a controlled gluten challenge, albeit with a relatively moderate amount of gluten (a regular diet contains 12 g of gluten daily, whereas the challenge involved 3 g daily) and for a short period of time,” Dr. Jabri said. The reduction of disease-associated symptoms and apparent improvement in quality of life with 100-mg dose added value to the findings, she said.

Future research areas include whether cross-reactive T cells, which were not analyzed in the current study, might “expand and become pathogenic after a long-term gluten challenge,” Dr. Jabri noted.

However, “ZED1227 is the first nondietary treatment that has preliminarily shown the capacity to prevent mucosal damage in persons with celiac disease,” she said.

“Although this trial is very encouraging, whether treatment with ZED1227, and more generally transglutaminase 2 inhibition, in patients with celiac disease will be efficient in real life and during long-term gluten exposure remains to be determined,” Dr. Jabri concluded.
 

Need for data on dosing consistency

“Celiac disease affects up to 2% of the population in many countries, and the main therapy of celiac disease is avoidance of gluten,” Kim Isaacs, MD, of the University of North Carolina, Chapel Hill, said in an interview. “This is challenging due to the ubiquitous nature of gluten in many food products,” she said. “Restrictive eating also affects social interaction which is often focused around food,” she added. “Availability of an oral therapy that is effective to treat celiac in the face of gluten exposure will have a profound impact on patients in terms of liberalization of dietary intake.”

Overall, “the changes in the villus height to crypt depth was similar between all the active treatment groups, whereas there was a dose-dependent reduction in transepithelial lymphocyte density,” Dr. Isaacs noted. “The symptom improvement was greatest in the 100-mg group, suggesting that symptoms may be related to a greater extent to the lymphocyte density than the minimal differences in villus height to crypt depth ratios seen in the active treatment groups,” she said.

Potential barriers to the use of the treatment include cost because “this will need to be a daily long-term therapy,” said Dr. Isaacs. “Compliance is a potential barrier as well,” she said. “This study looks at daily administration of the transglutaminase 2 inhibitor and shows a benefit, but it is not clear whether missing doses of the medication will have a prolonged impact on efficacy,” she emphasized. Consequently, long-term efficacy studies are needed, Dr. Isaacs said. Other research questions to answer include whether patients will become refractory to the beneficial effects over time, the effect of missing doses, and whether patients would lose all the benefits of the therapy if dosing is not consistent, she emphasized.

The study was funded by Dr. Falk Pharma. The researchers, as well as Dr. Jabri and Dr. Isaacs, had no financial conflicts to disclose. Dr. Isaacs is on the editorial advisory board of GI & Hepatology News.

A novel oral inhibitor of transglutaminase 2 appears to block gluten-induced mucosal damage in patients with celiac disease at three different doses, based on proof-of-concept trial data from 132 patients.

“Currently, no drug therapy reliably prevents the effects of dietary gluten or has been approved by regulators to treat celiac disease,” which remains an unmet need in these patients, many of whom struggle with symptoms even when they adhere to a gluten-free diet, wrote Detlef Schuppan, MD, of Johannes Gutenberg University of Mainz (Germany) and colleagues.

Celiac disease is driven in part by the enzyme transglutaminase 2, and a transglutaminase 2 inhibitor known as ZED1227 has been tested safely in phase 1 trials, they reported.

“ZED1227 targets the intestinal mucosa predominantly and thereby mediates protection; thus, it is unaffected by the complexity of the food matrix and is less dependent on the timing of ingestion of gluten-containing food,” the researchers explained.

In a study published in the New England Journal of Medicine, the researchers assessed the safety and efficacy of three dose levels of ZED1227. Adults with controlled celiac disease were randomized to doses of 10 mg (41 patients), 50 mg (41 patients), and 100 mg (41 patients), and 40 patients received a placebo. Of these, 35, 39, 28, and 30 patients, respectively, had sufficient duodenal biopsy samples for analysis.

Patients underwent a daily gluten challenge of 3 g for 6 weeks. At the end of 6 weeks, the primary study endpoint of attenuation of gluten-induced mucosal damage was measured by the ratio of villus height to crypt depth.

Patients in all three treatment groups showed significant attenuation of mucosal damage. The change in the average ratio of villus height to crypt depth compared to placebo in the 10-mg, 50-mg, and 100-mg groups was 0.44, 0.49, and 0.48, respectively, with P values equal to .001 in the 10-mg group and less than .001 in the 50-mg and 100-mg groups.

Adverse events were similar across all treatment groups and the placebo group, with the exception of a rash in three patients in the 100-mg group. A total of 74 patients reported adverse events, and the most common were headache, nausea, diarrhea, vomiting, and abdominal pain. The investigators determined that from 34% to 55% of the adverse events across groups were related to the study drug or placebo.

Two patients developed serious adverse events that were deemed related to the study drug or placebo; one patient in the 50-mg group developed migraine with aura, and one placebo patient developed ventricular extrasystoles. The patients recovered after discontinuing the drug or placebo.

Secondary endpoints included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score. Estimated changes in intraepithelial lymphocyte density, compared with placebo, were –2.7 cells per 100 epithelial cells in the 10-mg group, −4.2 cells per 100 epithelial cells in the 50-mg group, and −9.6 cells per 100 epithelial cells in the 100-mg group. Compared with those of patients taking placebo, the 6-week changes in Celiac Symptom Index scores and Celiac Disease Questionnaire scores suggested slight improvements in symptoms and quality of life for the 100-mg dose.

The study findings were limited by several factors including missing data and loss of several patients to follow-up, as well as the short trial duration and use of controlled gluten ingestion, the researchers noted. Larger studies involving real-world conditions of minor gluten ingestion are needed to support the preliminary signs of safety and efficacy, they said.

Study strengths include high levels of patient adherence to the treatment and the gluten challenge, they said. “Future studies of ZED1227 in more patients are needed to provide additional evidence of the safety and efficacy of the drug, potentially in real-life conditions with minor gluten ingestion,” they concluded.
 

Translating potential into practice

“An absence of mucosal damage is a critical criterion to ensure the long-term health of a patient, and this clinical trial in celiac disease meets this important endpoint,” Bana Jabri, MD, of the University of Chicago, wrote in an accompanying editorial.

The primary endpoint of no mucosal damage is “especially notable because it was achieved under a controlled gluten challenge, albeit with a relatively moderate amount of gluten (a regular diet contains 12 g of gluten daily, whereas the challenge involved 3 g daily) and for a short period of time,” Dr. Jabri said. The reduction of disease-associated symptoms and apparent improvement in quality of life with 100-mg dose added value to the findings, she said.

Future research areas include whether cross-reactive T cells, which were not analyzed in the current study, might “expand and become pathogenic after a long-term gluten challenge,” Dr. Jabri noted.

However, “ZED1227 is the first nondietary treatment that has preliminarily shown the capacity to prevent mucosal damage in persons with celiac disease,” she said.

“Although this trial is very encouraging, whether treatment with ZED1227, and more generally transglutaminase 2 inhibition, in patients with celiac disease will be efficient in real life and during long-term gluten exposure remains to be determined,” Dr. Jabri concluded.
 

Need for data on dosing consistency

“Celiac disease affects up to 2% of the population in many countries, and the main therapy of celiac disease is avoidance of gluten,” Kim Isaacs, MD, of the University of North Carolina, Chapel Hill, said in an interview. “This is challenging due to the ubiquitous nature of gluten in many food products,” she said. “Restrictive eating also affects social interaction which is often focused around food,” she added. “Availability of an oral therapy that is effective to treat celiac in the face of gluten exposure will have a profound impact on patients in terms of liberalization of dietary intake.”

Overall, “the changes in the villus height to crypt depth was similar between all the active treatment groups, whereas there was a dose-dependent reduction in transepithelial lymphocyte density,” Dr. Isaacs noted. “The symptom improvement was greatest in the 100-mg group, suggesting that symptoms may be related to a greater extent to the lymphocyte density than the minimal differences in villus height to crypt depth ratios seen in the active treatment groups,” she said.

Potential barriers to the use of the treatment include cost because “this will need to be a daily long-term therapy,” said Dr. Isaacs. “Compliance is a potential barrier as well,” she said. “This study looks at daily administration of the transglutaminase 2 inhibitor and shows a benefit, but it is not clear whether missing doses of the medication will have a prolonged impact on efficacy,” she emphasized. Consequently, long-term efficacy studies are needed, Dr. Isaacs said. Other research questions to answer include whether patients will become refractory to the beneficial effects over time, the effect of missing doses, and whether patients would lose all the benefits of the therapy if dosing is not consistent, she emphasized.

The study was funded by Dr. Falk Pharma. The researchers, as well as Dr. Jabri and Dr. Isaacs, had no financial conflicts to disclose. Dr. Isaacs is on the editorial advisory board of GI & Hepatology News.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.