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U.S. study finds racial, gender differences in surgical treatment of dermatofibrosarcoma protuberans
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Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
.
Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
.
Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.
In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.
Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”
In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.
The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.
“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM JAAD
First-in-class TYK inhibitor shows durable effect for psoriasis
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.
From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).
“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.
The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.
For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).
By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.
By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.
The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.
When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.
On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.
Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.
“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.
In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.
Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.
In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.
The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.
“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.
Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.
“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.
“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.
The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
A female toddler presents with an itchy yellow nodule
Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.
JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
What is on the differential?
Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.
Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.
Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.
Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.
Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.
References
Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.
Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).
Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.
Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.
Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.
JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
What is on the differential?
Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.
Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.
Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.
Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.
Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.
References
Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.
Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).
Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.
Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.
Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.
JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
What is on the differential?
Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.
Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.
Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.
Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.
Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.
References
Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.
Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).
Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.
Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.
NIAMS director reflects on her mentors, spotlights research projects underway
After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.
“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.
Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.
Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.
What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.
Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.
What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.
How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.
The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.
The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.
The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).
Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.
What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.
Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.
Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.
How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.
During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.
What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.
Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.
Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.
Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.
After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.
“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.
Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.
Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.
What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.
Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.
What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.
How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.
The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.
The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.
The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).
Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.
What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.
Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.
Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.
How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.
During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.
What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.
Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.
Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.
Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.
After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.
“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.
Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.
Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.
What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.
Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.
What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.
How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.
The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.
The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.
The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).
Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.
What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.
Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.
Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.
How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.
During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.
What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.
Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.
Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.
Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.
Management of pediatric food allergies evolving
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
The treatment of atopic dermatitis (AD) is undergoing a revolution thanks to biologics. Now, an allergist and a dietitian told pediatric dermatologists that the treatment of a related condition – food allergy – is also undergoing a dramatic transformation as the management approach evolves away from blanket avoidance of allergens.
“Over the past 15 years, we’ve seen a shift from a very passive approach where generally we just advised patients to avoid the things they’re allergic to,” said U.K. pediatric allergist Adam Fox, MBBS, MD, in a presentation at The World Congress of Pediatric Dermatology (WCPD) 2021 Annual Meeting. “Now, we have a much better understanding of how allergy develops and strategies to minimize the risk of allergy happening in the first place,” he said.
According to Carina Venter, PhD, RD, associate professor of pediatrics-allergy/immunology at the University of Colorado, Denver, who also spoke at the conference, an estimated 20% to 30% of patients with AD also have food allergies, and up to 90% of infants with cow’s milk allergy develop skin symptoms.
It may not be necessary for a breastfeeding mother to avoid food allergens if a child is allergic, said Dr. Fox, of Guy’s and St. Thomas’ NHS Foundation Trust, London. “A lot of parents will automatically assume that if their child has an egg or milk allergy, then it’s a good idea to completely eliminate that from their diet if they’re breastfeeding,” but it is “surprisingly uncommon” that this approach makes a difference, he said. “Less goes through the breast milk than people imagine,” he said.
He noted that eliminating foods from the breastfeeding mother’s diet may have negative consequences. “There’s always that risk that if you make life harder for the breastfeeding mom because they’re going to have to avoid all sorts of foods, they’ll be more likely to discontinue breastfeeding. You really need a compelling reason to stop the food.”
As for children themselves, Dr. Fox suggested that there’s often no connection between AD and food allergies. “What will commonly happen when you see and diagnose these kids is that their eczema has been quite significantly undertreated,” he said. “Once you just get them on the right [regimen], they don’t need to be cutting the food out of their diet. It’s just making their life unnecessarily harder.”
Dr. Venter said there may be little choice but to avoid a trigger food if a child develops AD with exposure. However, she noted, it’s important to understand that avoidance of certain foods could make the allergy – and AD – worse. “If you have a child or an adult with atopic dermatitis that’s not controlled by an optimal topical treatment, and you do consider avoidance, we need to be aware that development of more severe IgA-mediated symptoms can happen in a short period of time,” she said.
In a slide that Dr. Venter presented, the dilemma for physicians was expressed this way: “The potential benefit of food avoidance as a management strategy for some patients with AD must now be weighed against the strong evidence that unnecessarily avoiding a food in kids with AD increases the risk of developing anaphylaxis to that food.”
What should pediatric dermatologists do to balance the risks of allergen exposure to the risks that children will develop permanent allergies? Dr. Venter pointed to guidelines about AD that were developed by the U.K.’s National Institute for Health and Care Excellence. She also highlighted the International Milk Allergy in Primary Care recommendations.
She suggested considering creative ways to bypass complete avoidance and boost a child’s tolerance of allergens if possible. “If we’re going to keep a child with eczema on a mold-free diet for a longer period of time, is there perhaps a role for regularly introducing small amounts of yogurt or even small amounts of milk in the child’s diet to at least keep immune tolerance without necessarily aggravating eczema symptoms?”
Dr. Fox has consulted for DBV and Aimmune through his employer, NHS Trust. He serves as president of the British Society for Allergy and Clinical Immunology and as chair of the Allergy UK Health Advisory Board, both of which receive funding from drug companies. Dr. Venter has received support for allergy-related research from the National Peanut Board.
A version of this article first appeared on Medscape.com.
Acceptance of biosimilars grows but greater use may hinge on switching, interchangeability studies
It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.
So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.
“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”
After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.
Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.
Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.
“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.
The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.
Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.
In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”
Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”
Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.
Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.
Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.
Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.
From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States
Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.
In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.
But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.
It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.
In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.
Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.
“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”
Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.
But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.
Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.
“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.
Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.
However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).
Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.
In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.
But she received good news recently: Her new plan will cover Remicade.
“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.
So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.
“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”
After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.
Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.
Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.
“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.
The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.
Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.
In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”
Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”
Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.
Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.
Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.
Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.
From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States
Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.
In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.
But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.
It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.
In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.
Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.
“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”
Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.
But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.
Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.
“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.
Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.
However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).
Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.
In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.
But she received good news recently: Her new plan will cover Remicade.
“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.
So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.
“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”
After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.
Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.
Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.
“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.
The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.
Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.
In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”
Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”
Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.
Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.
Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.
Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.
From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States
Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.
In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.
But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.
It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.
In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.
Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.
“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”
Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.
But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.
Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.
“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.
Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.
However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).
Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.
In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.
But she received good news recently: Her new plan will cover Remicade.
“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Pruritic blistering rash
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.
LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.1 It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.1
LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.
It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.2 Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.
Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.1) Follow-up in 1 month was scheduled.
Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
1. Hall III RP, Rao C. Linear IgA bullous dermatosis. Uptodate. Updated September 24, 2020. Accessed September 26, 2021. https://www.uptodate.com/contents/linear-iga-bullous-dermatosis#!
2. Leiferman K. Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid. Uptodate. Updated June 30, 2021. Accessed September, 2021. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bullous-pemphigoid-and-mucous-membrane-pemphigoid#!
More severe psoriasis linked to an increased risk of PsA
Factors that predict the development of psoriasis in patients with psoriasis include nail, inverse, and scalp psoriasis; family history of PsA; as well as severity of skin disease. And like psoriasis, “PsA is associated with a multitude of comorbidities, including cardiovascular disease, metabolic syndrome, Crohn’s disease, obesity, diabetes, uveitis, anxiety, and depression, with correspondingly higher healthcare utilization and direct healthcare costs,” wrote corresponding author Joseph F. Merola, MD, MMSc, and colleagues. The study was published online in the Journal of the American Academy of Dermatology. “Timely and accurate diagnosis of PsA is important for improved patient outcomes and appropriate disease management and may prevent prolonged inflammation that leads to structural joint damage and worsening physical function,” they added.
The mean time of onset of PsA among patients with psoriasis who develop PsA is 10 years after the first signs of psoriasis appear. An estimated 20%-30% of patients with psoriasis have a concurrent diagnosis of PsA, and the annual incidence of PsA has been reported to be 2.7 cases per 100 patients with psoriasis. While previous studies have suggested that a higher incidence of PsA is associated with greater disease severity, there are limited data in the United States on the topic.
For the study, Dr. Merola, a dermatologist and rheumatologist who directs the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, and his colleagues drew from the Optum EHR database to identify adult patients newly diagnosed with psoriasis between Jan. 1, 2009, and March 31, 2019. Patients diagnosed with psoriasis or PsA prior to the index date were excluded from the analysis for evaluation of incidence but included for evaluation of prevalence. The patients were followed from the index date until the earliest PsA event, death, or end of study or follow-up, whichever came first. The researchers calculated the incidence of PsA among adults with psoriasis as the number of incident PsA events divided by the number of patient-years (PY) at risk, which was reported as the raw incidence per 100 psoriasis PY. They calculated the prevalence of PsA among adults with psoriasis as “the number of prevalent PsA events divided by the number of eligible patients with [psoriasis] and reported by years in the follow-up period,” which was a median of 3.7 years.
A total of 114,868 patients were included in the analysis. At baseline, their mean age was 54 years, 53% were female, 89% were White, and 39% were obese. Most patients (102,553) were on nonsystemic agents during the year after their psoriasis diagnosis, while 6,345 were on nonbiologic systemic therapies (NBSTs) and 5,970 were on biologics. The researchers classified patients as having mild psoriasis if they were taking nonsystemic agents, moderate disease if they were taking NBSTs, or severe disease if they were taking biologics.
The overall incidence rate of PsA was 2.9 events per 100 PY and increased by severity of disease. When calculated by severity, the incidence was 2.1 events per 100 PY for patients with mild psoriasis, 9.9 events per 100 PY for those with moderate psoriasis, and 17.6 events per 100 PY for those with severe psoriasis.
When the researchers excluded patients diagnosed with PsA up to 1 year after being diagnosed with psoriasis, the overall incidence was lower (1.7 events per 100 PY), with similar trends for categories of treatment severity. Specifically, the incidence was 1.5, 3.1, and 4.7 events per 100 PY among those with mild, moderate, and severe psoriasis, based on their treatment groups, respectively.
Among the 120,523 patients with psoriasis who were eligible for the assessment of prevalence of PsA, the overall 5-year prevalence of PsA was 14.2% and rose with severity of disease: 9.9% in patients with mild psoriasis, 35% in patients with moderate psoriasis, and 54.9% in patients with severe psoriasis.
Other predictors of PsA onset for both index-date cohorts included weight of 90 kg or greater, female gender, age group 25-65 years (compared with the age group over 65 years), and rheumatic risk factors such as wrist pain and unspecified rheumatism.
“To ensure timely diagnosis and treatment for management and prevention of PsA, patients with [psoriasis] should be routinely screened, especially those with more severe disease and other PsA risk factors,” the authors advised.
Dr. Merola and colleagues acknowledged certain limitations of their analysis, including the potential for selection bias and its reliance on EHR data which “lacked clinical measures of disease severity such as the PASI, and data on BSA were not available for all study participants; therefore, treatment groups were used as a surrogate for disease severity,” they wrote. “As a result, some patients may have been miscategorized, especially patients with severe disease who were untreated.”
The study was sponsored by Novartis. Dr. Merola disclosed that he is a consultant and/or investigator for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharmaceuticals, Biogen, Pfizer, EMD Serono, Avotres, and LEO Pharma. Four authors are Novartis employees, or employees of a consulting company that provides services to Novartis; and another author disclosed serving as an investigator or consultant for several pharmaceutical companies, including Novartis.
Factors that predict the development of psoriasis in patients with psoriasis include nail, inverse, and scalp psoriasis; family history of PsA; as well as severity of skin disease. And like psoriasis, “PsA is associated with a multitude of comorbidities, including cardiovascular disease, metabolic syndrome, Crohn’s disease, obesity, diabetes, uveitis, anxiety, and depression, with correspondingly higher healthcare utilization and direct healthcare costs,” wrote corresponding author Joseph F. Merola, MD, MMSc, and colleagues. The study was published online in the Journal of the American Academy of Dermatology. “Timely and accurate diagnosis of PsA is important for improved patient outcomes and appropriate disease management and may prevent prolonged inflammation that leads to structural joint damage and worsening physical function,” they added.
The mean time of onset of PsA among patients with psoriasis who develop PsA is 10 years after the first signs of psoriasis appear. An estimated 20%-30% of patients with psoriasis have a concurrent diagnosis of PsA, and the annual incidence of PsA has been reported to be 2.7 cases per 100 patients with psoriasis. While previous studies have suggested that a higher incidence of PsA is associated with greater disease severity, there are limited data in the United States on the topic.
For the study, Dr. Merola, a dermatologist and rheumatologist who directs the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, and his colleagues drew from the Optum EHR database to identify adult patients newly diagnosed with psoriasis between Jan. 1, 2009, and March 31, 2019. Patients diagnosed with psoriasis or PsA prior to the index date were excluded from the analysis for evaluation of incidence but included for evaluation of prevalence. The patients were followed from the index date until the earliest PsA event, death, or end of study or follow-up, whichever came first. The researchers calculated the incidence of PsA among adults with psoriasis as the number of incident PsA events divided by the number of patient-years (PY) at risk, which was reported as the raw incidence per 100 psoriasis PY. They calculated the prevalence of PsA among adults with psoriasis as “the number of prevalent PsA events divided by the number of eligible patients with [psoriasis] and reported by years in the follow-up period,” which was a median of 3.7 years.
A total of 114,868 patients were included in the analysis. At baseline, their mean age was 54 years, 53% were female, 89% were White, and 39% were obese. Most patients (102,553) were on nonsystemic agents during the year after their psoriasis diagnosis, while 6,345 were on nonbiologic systemic therapies (NBSTs) and 5,970 were on biologics. The researchers classified patients as having mild psoriasis if they were taking nonsystemic agents, moderate disease if they were taking NBSTs, or severe disease if they were taking biologics.
The overall incidence rate of PsA was 2.9 events per 100 PY and increased by severity of disease. When calculated by severity, the incidence was 2.1 events per 100 PY for patients with mild psoriasis, 9.9 events per 100 PY for those with moderate psoriasis, and 17.6 events per 100 PY for those with severe psoriasis.
When the researchers excluded patients diagnosed with PsA up to 1 year after being diagnosed with psoriasis, the overall incidence was lower (1.7 events per 100 PY), with similar trends for categories of treatment severity. Specifically, the incidence was 1.5, 3.1, and 4.7 events per 100 PY among those with mild, moderate, and severe psoriasis, based on their treatment groups, respectively.
Among the 120,523 patients with psoriasis who were eligible for the assessment of prevalence of PsA, the overall 5-year prevalence of PsA was 14.2% and rose with severity of disease: 9.9% in patients with mild psoriasis, 35% in patients with moderate psoriasis, and 54.9% in patients with severe psoriasis.
Other predictors of PsA onset for both index-date cohorts included weight of 90 kg or greater, female gender, age group 25-65 years (compared with the age group over 65 years), and rheumatic risk factors such as wrist pain and unspecified rheumatism.
“To ensure timely diagnosis and treatment for management and prevention of PsA, patients with [psoriasis] should be routinely screened, especially those with more severe disease and other PsA risk factors,” the authors advised.
Dr. Merola and colleagues acknowledged certain limitations of their analysis, including the potential for selection bias and its reliance on EHR data which “lacked clinical measures of disease severity such as the PASI, and data on BSA were not available for all study participants; therefore, treatment groups were used as a surrogate for disease severity,” they wrote. “As a result, some patients may have been miscategorized, especially patients with severe disease who were untreated.”
The study was sponsored by Novartis. Dr. Merola disclosed that he is a consultant and/or investigator for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharmaceuticals, Biogen, Pfizer, EMD Serono, Avotres, and LEO Pharma. Four authors are Novartis employees, or employees of a consulting company that provides services to Novartis; and another author disclosed serving as an investigator or consultant for several pharmaceutical companies, including Novartis.
Factors that predict the development of psoriasis in patients with psoriasis include nail, inverse, and scalp psoriasis; family history of PsA; as well as severity of skin disease. And like psoriasis, “PsA is associated with a multitude of comorbidities, including cardiovascular disease, metabolic syndrome, Crohn’s disease, obesity, diabetes, uveitis, anxiety, and depression, with correspondingly higher healthcare utilization and direct healthcare costs,” wrote corresponding author Joseph F. Merola, MD, MMSc, and colleagues. The study was published online in the Journal of the American Academy of Dermatology. “Timely and accurate diagnosis of PsA is important for improved patient outcomes and appropriate disease management and may prevent prolonged inflammation that leads to structural joint damage and worsening physical function,” they added.
The mean time of onset of PsA among patients with psoriasis who develop PsA is 10 years after the first signs of psoriasis appear. An estimated 20%-30% of patients with psoriasis have a concurrent diagnosis of PsA, and the annual incidence of PsA has been reported to be 2.7 cases per 100 patients with psoriasis. While previous studies have suggested that a higher incidence of PsA is associated with greater disease severity, there are limited data in the United States on the topic.
For the study, Dr. Merola, a dermatologist and rheumatologist who directs the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, and his colleagues drew from the Optum EHR database to identify adult patients newly diagnosed with psoriasis between Jan. 1, 2009, and March 31, 2019. Patients diagnosed with psoriasis or PsA prior to the index date were excluded from the analysis for evaluation of incidence but included for evaluation of prevalence. The patients were followed from the index date until the earliest PsA event, death, or end of study or follow-up, whichever came first. The researchers calculated the incidence of PsA among adults with psoriasis as the number of incident PsA events divided by the number of patient-years (PY) at risk, which was reported as the raw incidence per 100 psoriasis PY. They calculated the prevalence of PsA among adults with psoriasis as “the number of prevalent PsA events divided by the number of eligible patients with [psoriasis] and reported by years in the follow-up period,” which was a median of 3.7 years.
A total of 114,868 patients were included in the analysis. At baseline, their mean age was 54 years, 53% were female, 89% were White, and 39% were obese. Most patients (102,553) were on nonsystemic agents during the year after their psoriasis diagnosis, while 6,345 were on nonbiologic systemic therapies (NBSTs) and 5,970 were on biologics. The researchers classified patients as having mild psoriasis if they were taking nonsystemic agents, moderate disease if they were taking NBSTs, or severe disease if they were taking biologics.
The overall incidence rate of PsA was 2.9 events per 100 PY and increased by severity of disease. When calculated by severity, the incidence was 2.1 events per 100 PY for patients with mild psoriasis, 9.9 events per 100 PY for those with moderate psoriasis, and 17.6 events per 100 PY for those with severe psoriasis.
When the researchers excluded patients diagnosed with PsA up to 1 year after being diagnosed with psoriasis, the overall incidence was lower (1.7 events per 100 PY), with similar trends for categories of treatment severity. Specifically, the incidence was 1.5, 3.1, and 4.7 events per 100 PY among those with mild, moderate, and severe psoriasis, based on their treatment groups, respectively.
Among the 120,523 patients with psoriasis who were eligible for the assessment of prevalence of PsA, the overall 5-year prevalence of PsA was 14.2% and rose with severity of disease: 9.9% in patients with mild psoriasis, 35% in patients with moderate psoriasis, and 54.9% in patients with severe psoriasis.
Other predictors of PsA onset for both index-date cohorts included weight of 90 kg or greater, female gender, age group 25-65 years (compared with the age group over 65 years), and rheumatic risk factors such as wrist pain and unspecified rheumatism.
“To ensure timely diagnosis and treatment for management and prevention of PsA, patients with [psoriasis] should be routinely screened, especially those with more severe disease and other PsA risk factors,” the authors advised.
Dr. Merola and colleagues acknowledged certain limitations of their analysis, including the potential for selection bias and its reliance on EHR data which “lacked clinical measures of disease severity such as the PASI, and data on BSA were not available for all study participants; therefore, treatment groups were used as a surrogate for disease severity,” they wrote. “As a result, some patients may have been miscategorized, especially patients with severe disease who were untreated.”
The study was sponsored by Novartis. Dr. Merola disclosed that he is a consultant and/or investigator for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharmaceuticals, Biogen, Pfizer, EMD Serono, Avotres, and LEO Pharma. Four authors are Novartis employees, or employees of a consulting company that provides services to Novartis; and another author disclosed serving as an investigator or consultant for several pharmaceutical companies, including Novartis.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
New virus causing ‘Alaskapox’ detected in two more cases
Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.
This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.
Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.
Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.
In both cases, the women recovered completely.
Smallpox-like illness
Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.
Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.
All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.
The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.
None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.
There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.
A version of this article first appeared on WebMD.com.
Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.
This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.
Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.
Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.
In both cases, the women recovered completely.
Smallpox-like illness
Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.
Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.
All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.
The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.
None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.
There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.
A version of this article first appeared on WebMD.com.
Both people were diagnosed after receiving urgent care in a Fairbanks-area clinic. One was a child with a sore on the left elbow, along with fever and swollen lymph nodes. And the other was an unrelated middle-aged woman with a pox mark on her leg, swollen lymph nodes, and joint pain. In both cases, symptoms improved within 3 weeks.
This isn’t the first time the so-called Alaskapox virus has been detected in the region. In 2015, a woman living near Fairbanks turned up at her doctor’s office with a single reddened pox-like mark on her upper arm and a feeling of fatigue.
Sampling of the pox mark showed that it was caused by a previously unidentified virus of the same family as smallpox and cowpox.
Five years later, another woman showed up with similar signs and symptoms, and her pox also proved to be the result of what public health experts started calling the Alaskapox virus.
In both cases, the women recovered completely.
Smallpox-like illness
Public health sleuths figured out that in three of the four cases, the patients lived in a home with a cat or cats, and one of these cats was known to hunt small animals.
Experts already knew that cats mingling in cow pastures and sickened by cattle virus had helped cowpox make the leap from bovines to humans. And just as in the case of cowpox, they suspected that cats might again be spreading this new virus to people, too.
All four of the infected people lived in sparsely populated areas amid forests. Officials laid animal traps where some of the affected people lived and identified the virus in several species of small wild animals.
The animals that turned up most often with Alaskapox were small mouse-like voles. The rodents with rounded muzzles are known for burrowing in the region. And scientists suspect the Alaskapox virus makes its way from these wild animals to humans through their pet cats or possibly by direct exposure outdoors.
None of the four people identified so far with Alaskapox knew each other or interacted, so officials also suspect that there are more cases going unrecognized, possibly because the symptoms are mild or nonexistent.
There are no documented cases of person-to-person transmission of Alaskapox, according to public health officials monitoring the small number of cases. But other pox viruses can spread by direct contact with skin lesions, so clinicians are recommending that people cover wounds with bandages. Three of the people with Alaskapox mistook their lesions at first for a bite from a spider or insect.
A version of this article first appeared on WebMD.com.
Itchy patch on the clavicle
A broad shave biopsy, utilizing dermoscopy to help delineate the edges of the lesion, confirmed the diagnosis of melanoma in situ, superficial spreading type.
From the standpoint of ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing), this lesion was quite worrisome. Helpful clues on clinical exam included the asymmetry, border irregularity, color variations (brown, pink, and red), size, and history of change. A dermatoscope helped to refine the features of the lesion and highlighted the melanocytic-specific characteristics of its pigment network, streaks, and regression structures (pepper-like gray dots and white streaks).1
A broad shave biopsy allows a very thorough evaluation of such a heterogeneous lesion. A smaller punch biopsy can miss the most worrisome features. That said, a smaller punch biopsy is sometimes necessary in challenging anatomic locations, such as the palm or sole.
Patients given a diagnosis of melanoma in situ should undergo wide local excision with 5-mm margins or 1-cm margins in instances of lentigo maligna, which is a subtype of melanoma in situ with a higher risk of clinically uncertain margins. (A sentinel lymph node biopsy is not recommended for melanoma in situ, as the Breslow depth is 0 mm.)
For this patient, an in-office wide local excision was performed down to the fascia and the skin was repaired in a layered fashion. The plan for this patient was for him to return for skin examinations 3 to 4 times in the first year of diagnosis, followed by twice annually until he was 5 years from his diagnosis. After that, he would undergo annual skin exams.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
Ribero S, Moscarella E, Ferrara G, et al. Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. J Eur Acad Dermatol Venereol. 2016;30:2030-2037. doi: 10.1111/jdv.13815
A broad shave biopsy, utilizing dermoscopy to help delineate the edges of the lesion, confirmed the diagnosis of melanoma in situ, superficial spreading type.
From the standpoint of ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing), this lesion was quite worrisome. Helpful clues on clinical exam included the asymmetry, border irregularity, color variations (brown, pink, and red), size, and history of change. A dermatoscope helped to refine the features of the lesion and highlighted the melanocytic-specific characteristics of its pigment network, streaks, and regression structures (pepper-like gray dots and white streaks).1
A broad shave biopsy allows a very thorough evaluation of such a heterogeneous lesion. A smaller punch biopsy can miss the most worrisome features. That said, a smaller punch biopsy is sometimes necessary in challenging anatomic locations, such as the palm or sole.
Patients given a diagnosis of melanoma in situ should undergo wide local excision with 5-mm margins or 1-cm margins in instances of lentigo maligna, which is a subtype of melanoma in situ with a higher risk of clinically uncertain margins. (A sentinel lymph node biopsy is not recommended for melanoma in situ, as the Breslow depth is 0 mm.)
For this patient, an in-office wide local excision was performed down to the fascia and the skin was repaired in a layered fashion. The plan for this patient was for him to return for skin examinations 3 to 4 times in the first year of diagnosis, followed by twice annually until he was 5 years from his diagnosis. After that, he would undergo annual skin exams.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
A broad shave biopsy, utilizing dermoscopy to help delineate the edges of the lesion, confirmed the diagnosis of melanoma in situ, superficial spreading type.
From the standpoint of ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing), this lesion was quite worrisome. Helpful clues on clinical exam included the asymmetry, border irregularity, color variations (brown, pink, and red), size, and history of change. A dermatoscope helped to refine the features of the lesion and highlighted the melanocytic-specific characteristics of its pigment network, streaks, and regression structures (pepper-like gray dots and white streaks).1
A broad shave biopsy allows a very thorough evaluation of such a heterogeneous lesion. A smaller punch biopsy can miss the most worrisome features. That said, a smaller punch biopsy is sometimes necessary in challenging anatomic locations, such as the palm or sole.
Patients given a diagnosis of melanoma in situ should undergo wide local excision with 5-mm margins or 1-cm margins in instances of lentigo maligna, which is a subtype of melanoma in situ with a higher risk of clinically uncertain margins. (A sentinel lymph node biopsy is not recommended for melanoma in situ, as the Breslow depth is 0 mm.)
For this patient, an in-office wide local excision was performed down to the fascia and the skin was repaired in a layered fashion. The plan for this patient was for him to return for skin examinations 3 to 4 times in the first year of diagnosis, followed by twice annually until he was 5 years from his diagnosis. After that, he would undergo annual skin exams.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
Ribero S, Moscarella E, Ferrara G, et al. Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. J Eur Acad Dermatol Venereol. 2016;30:2030-2037. doi: 10.1111/jdv.13815
Ribero S, Moscarella E, Ferrara G, et al. Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. J Eur Acad Dermatol Venereol. 2016;30:2030-2037. doi: 10.1111/jdv.13815
