Who would have thought we would need to refresh our knowledge on polio virus in 2022? Fate seems cruel to add this concern on the heels of SARS-CoV-2, monkeypox, abnormal seasons for RSV, acute flaccid myelitis (AFM) linked to enteroviruses, and a summer of parechovirus causing infant meningitis. But confirmation that indeed an adult had polio with paralytic disease raises concerns among public health groups and ordinary citizens alike, particularly those who remember polio in its heyday.

History: In the summer of 1952, polio was among the most feared diseases on the planet. Families were advised to not allow children to congregate in groups or use public swimming pools; little league baseball games were being canceled and there was talk of not opening schools for the fall. Every parent’s nightmare seemed to be the nonspecific febrile summer illness that led to paralytic sequelae. TV news included videos of the iron lung wards in hospitals across the country. Medical providers felt powerless, only able to give nonspecific preventive advice. There was no specific antiviral (there still isn’t) and vaccines seemed a long way off.

Then came the news that Dr. Jonas Salk’s group had gotten an inactivated polio vaccine (IPV) approved for general use in 1955. Families were excited to have their children vaccinated. Paralytic polio cases dropped like a rock from approximately 22,000/year in 1952 to approximately 2,200 in 1956. A surge to near 6,000 cases in 1959 led to Dr. Albert Sabin’s oral polio vaccine (OPV), which supplanted IPV in 1961. OPV had the advantages of: 1) Inducing mucosal as well as serum antibodies, 2) more durable responses, and 3) immunity in unvaccinated persons exposed to vaccine virus that had been shed in stools into wastewater and rivers.

By 1964, polio had nearly disappeared. The last wild-type indigenous U.S. case was in 1979. By 1994, all the Americas were declared polio free. Because the only U.S. paralytic polio cases thereafter were foreign imports or were associated with oral vaccine strains (so-called vaccine-associated paralytic polio [VAPP]), OPV was replaced by an enhanced IPV in 2000 to prevent further VAPP.

Polio facts: Polio is asymptomatic in about 70% of infections. Among the 30% with symptoms, paralysis occurs infrequently, with the overall rate of paralytic infections being 0.5% (rate varies by virus type with type 3 having the highest rate).¹ Why then was the world so afraid of polio? If every person in a U.S. birth cohort (about 3.7 million) was unvaccinated and became infected with poliovirus, more than 18,000 would get paralytic polio and almost 1,300 would die. Of note, adults have a higher chance of paralytic polio after infection than children.

Concerns in 2022: Persons vaccinated with at least three doses of either IPV or OPV have historically been protected from paralytic polio (99% protection). But are we sure that the United States remains protected against polio after 2 decades of IPV being the only vaccine? Polio could be reintroduced at any time to the United States from countries with reported cases that likely arose because of low vaccination rates related to war, famine, or political upheavals (Malawi, Mozambique, Nigeria, Pakistan, and Afghanistan).² The proof? The recent confirmed New York case.

International efforts resulted in global eradication of two polio wild-types viruses (type 2 in 2015 and type 3 in 2019). Nevertheless, vaccine-derived, virulent polio virus (VDPV) type 2 and VDPV-3 still circulate in some areas, particularly Africa (VDPV-2) and Israel (VDPV-3). The above-mentioned U.S. case is an unvaccinated adult traveler who went to an area where VDPV-2 circulates and developed disease after returning home.³ So, it was not an indigenous reappearance in the United States and it was not a breakthrough case in a vaccinated person. But it is sobering to realize that all who are unvaccinated remain at risk for paralytic polio in 2022, particularly because vaccination rates declined nearly everywhere during the initial COVID-19 pandemic. We are still catching up, with vaccination rates under 50% in some ZIP codes.⁴

Are VDPVs circulating in some parts of the United States? Interestingly, wastewater surveillance programs may be the most economical and practical way to perform polio surveillance. Such a program detected polio virus in London wastewater in June 2022.⁵ New York has recently detected polio in wastewater during testing begun because of the recent case.⁶

Good news: For paralytic polio, seropositivity at any titer indicates protection, so U.S. serosurveillance data would also be informative. How durable is polio protection in the IPV era? Available data suggest that even though we have used only IPV these past 20 years, seropositivity rates among vaccinees with at least three doses of either IPV or OPV should persist for decades and likely for life. Even before polio became a concern this year, the Centers for Disease Control and Prevention, being proactive, wanted to ensure that the enhanced IPV was producing durable immunity and that persons of all ages remained seropositive to the three polio virus types over 10 years after discontinuing OPV use in 2012.

The CDC collaborated with investigators in Kansas City, Mo., to evaluate titers and seropositivity to all three types in a 2- to 85-year-old otherwise healthy cohort with demographics that mirrored the 2010 census for the Kansas City region, which in turn mirrored the national 2021 census data.⁷ There were approximately 100 persons in each age cohort, with 200 below age 11 years (the cohort that had received only IPV). Serology was performed at the CDC.

Overall seropositivity rates were high, but lower for type 3 (83.3%) and type 2 (90.7%) than type 1 (94.4%). Of note, most of those seronegative for one or more types were among 2- to 3-year-olds who had not completed their full IPV series, with most seronegative results being against polio types 1 and 3. Further, five, who were confirmed as having received no polio vaccine, were seronegative for all three types. Two with no available vaccine records (over 18 years old) were also seronegative for all three types.

So, regardless of the era in which one got polio vaccine, vaccine protection appears to persist indefinitely after three doses. Even 80-year-olds were still seropositive if they had three doses. We can confidently reassure our patients that the vaccine still works; the persons who need to fear polio in 2022 are those who are not vaccinated or have had fewer than three doses, particularly if they travel to areas of persistent polio. Wild type 1 virus persists in a few countries as does VDPV type 2 and VDPV type 3. Importantly, wild type 2 and wild type 3 (with the lowest seropositivity in 2012 study) have been eliminated globally so the only circulating type 2 and type 3 polio virus is VDPV in a few countries. Travel to these countries warrants review of polio vaccine records and CDC or WHO current recommendations for travelers to those countries.
 

Dr. Harrison is a professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.

References

1. Poliomyelitis. World Health Organization fact sheet, 2022 Jul 4..

2. Franco-Paredes C et al. Lancet Infect Dis. 2022 Aug 16. doi: 10.1016/S1473-3099(22)00548-5.

3. Link-Gelles R et al. MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1065-8.

4. “Polio vaccination rate for 2-year-olds is as low as 37% in parts of N.Y. county where paralysis case was found,” NBC News, Erika Edwards, 2022 Aug 16. 5. Vaccine-derived poliovirus type 2 (VDPV2) detected in environmental samples in London. Polioeradication.org. 2022 Jun 22.

6. “NYSDOH and NYCDOHMH wastewater monitoring identifies polio in New York City and urges unvaccinated New Yorkers to get vaccinated now,” nyc.gov. 2022 Aug 12.

7. Wallace GS et al. Hum Vaccin Immunother. 2017;13(4):776-83.

Who would have thought we would need to refresh our knowledge on polio virus in 2022? Fate seems cruel to add this concern on the heels of SARS-CoV-2, monkeypox, abnormal seasons for RSV, acute flaccid myelitis (AFM) linked to enteroviruses, and a summer of parechovirus causing infant meningitis. But confirmation that indeed an adult had polio with paralytic disease raises concerns among public health groups and ordinary citizens alike, particularly those who remember polio in its heyday.

History: In the summer of 1952, polio was among the most feared diseases on the planet. Families were advised to not allow children to congregate in groups or use public swimming pools; little league baseball games were being canceled and there was talk of not opening schools for the fall. Every parent’s nightmare seemed to be the nonspecific febrile summer illness that led to paralytic sequelae. TV news included videos of the iron lung wards in hospitals across the country. Medical providers felt powerless, only able to give nonspecific preventive advice. There was no specific antiviral (there still isn’t) and vaccines seemed a long way off.

Then came the news that Dr. Jonas Salk’s group had gotten an inactivated polio vaccine (IPV) approved for general use in 1955. Families were excited to have their children vaccinated. Paralytic polio cases dropped like a rock from approximately 22,000/year in 1952 to approximately 2,200 in 1956. A surge to near 6,000 cases in 1959 led to Dr. Albert Sabin’s oral polio vaccine (OPV), which supplanted IPV in 1961. OPV had the advantages of: 1) Inducing mucosal as well as serum antibodies, 2) more durable responses, and 3) immunity in unvaccinated persons exposed to vaccine virus that had been shed in stools into wastewater and rivers.

By 1964, polio had nearly disappeared. The last wild-type indigenous U.S. case was in 1979. By 1994, all the Americas were declared polio free. Because the only U.S. paralytic polio cases thereafter were foreign imports or were associated with oral vaccine strains (so-called vaccine-associated paralytic polio [VAPP]), OPV was replaced by an enhanced IPV in 2000 to prevent further VAPP.

Polio facts: Polio is asymptomatic in about 70% of infections. Among the 30% with symptoms, paralysis occurs infrequently, with the overall rate of paralytic infections being 0.5% (rate varies by virus type with type 3 having the highest rate).¹ Why then was the world so afraid of polio? If every person in a U.S. birth cohort (about 3.7 million) was unvaccinated and became infected with poliovirus, more than 18,000 would get paralytic polio and almost 1,300 would die. Of note, adults have a higher chance of paralytic polio after infection than children.

Concerns in 2022: Persons vaccinated with at least three doses of either IPV or OPV have historically been protected from paralytic polio (99% protection). But are we sure that the United States remains protected against polio after 2 decades of IPV being the only vaccine? Polio could be reintroduced at any time to the United States from countries with reported cases that likely arose because of low vaccination rates related to war, famine, or political upheavals (Malawi, Mozambique, Nigeria, Pakistan, and Afghanistan).² The proof? The recent confirmed New York case.

International efforts resulted in global eradication of two polio wild-types viruses (type 2 in 2015 and type 3 in 2019). Nevertheless, vaccine-derived, virulent polio virus (VDPV) type 2 and VDPV-3 still circulate in some areas, particularly Africa (VDPV-2) and Israel (VDPV-3). The above-mentioned U.S. case is an unvaccinated adult traveler who went to an area where VDPV-2 circulates and developed disease after returning home.³ So, it was not an indigenous reappearance in the United States and it was not a breakthrough case in a vaccinated person. But it is sobering to realize that all who are unvaccinated remain at risk for paralytic polio in 2022, particularly because vaccination rates declined nearly everywhere during the initial COVID-19 pandemic. We are still catching up, with vaccination rates under 50% in some ZIP codes.⁴

Are VDPVs circulating in some parts of the United States? Interestingly, wastewater surveillance programs may be the most economical and practical way to perform polio surveillance. Such a program detected polio virus in London wastewater in June 2022.⁵ New York has recently detected polio in wastewater during testing begun because of the recent case.⁶

Good news: For paralytic polio, seropositivity at any titer indicates protection, so U.S. serosurveillance data would also be informative. How durable is polio protection in the IPV era? Available data suggest that even though we have used only IPV these past 20 years, seropositivity rates among vaccinees with at least three doses of either IPV or OPV should persist for decades and likely for life. Even before polio became a concern this year, the Centers for Disease Control and Prevention, being proactive, wanted to ensure that the enhanced IPV was producing durable immunity and that persons of all ages remained seropositive to the three polio virus types over 10 years after discontinuing OPV use in 2012.

The CDC collaborated with investigators in Kansas City, Mo., to evaluate titers and seropositivity to all three types in a 2- to 85-year-old otherwise healthy cohort with demographics that mirrored the 2010 census for the Kansas City region, which in turn mirrored the national 2021 census data.⁷ There were approximately 100 persons in each age cohort, with 200 below age 11 years (the cohort that had received only IPV). Serology was performed at the CDC.

Overall seropositivity rates were high, but lower for type 3 (83.3%) and type 2 (90.7%) than type 1 (94.4%). Of note, most of those seronegative for one or more types were among 2- to 3-year-olds who had not completed their full IPV series, with most seronegative results being against polio types 1 and 3. Further, five, who were confirmed as having received no polio vaccine, were seronegative for all three types. Two with no available vaccine records (over 18 years old) were also seronegative for all three types.

So, regardless of the era in which one got polio vaccine, vaccine protection appears to persist indefinitely after three doses. Even 80-year-olds were still seropositive if they had three doses. We can confidently reassure our patients that the vaccine still works; the persons who need to fear polio in 2022 are those who are not vaccinated or have had fewer than three doses, particularly if they travel to areas of persistent polio. Wild type 1 virus persists in a few countries as does VDPV type 2 and VDPV type 3. Importantly, wild type 2 and wild type 3 (with the lowest seropositivity in 2012 study) have been eliminated globally so the only circulating type 2 and type 3 polio virus is VDPV in a few countries. Travel to these countries warrants review of polio vaccine records and CDC or WHO current recommendations for travelers to those countries.
 

Dr. Harrison is a professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.

References

1. Poliomyelitis. World Health Organization fact sheet, 2022 Jul 4..

2. Franco-Paredes C et al. Lancet Infect Dis. 2022 Aug 16. doi: 10.1016/S1473-3099(22)00548-5.

3. Link-Gelles R et al. MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1065-8.

4. “Polio vaccination rate for 2-year-olds is as low as 37% in parts of N.Y. county where paralysis case was found,” NBC News, Erika Edwards, 2022 Aug 16. 5. Vaccine-derived poliovirus type 2 (VDPV2) detected in environmental samples in London. Polioeradication.org. 2022 Jun 22.

6. “NYSDOH and NYCDOHMH wastewater monitoring identifies polio in New York City and urges unvaccinated New Yorkers to get vaccinated now,” nyc.gov. 2022 Aug 12.

7. Wallace GS et al. Hum Vaccin Immunother. 2017;13(4):776-83.

Who would have thought we would need to refresh our knowledge on polio virus in 2022? Fate seems cruel to add this concern on the heels of SARS-CoV-2, monkeypox, abnormal seasons for RSV, acute flaccid myelitis (AFM) linked to enteroviruses, and a summer of parechovirus causing infant meningitis. But confirmation that indeed an adult had polio with paralytic disease raises concerns among public health groups and ordinary citizens alike, particularly those who remember polio in its heyday.

History: In the summer of 1952, polio was among the most feared diseases on the planet. Families were advised to not allow children to congregate in groups or use public swimming pools; little league baseball games were being canceled and there was talk of not opening schools for the fall. Every parent’s nightmare seemed to be the nonspecific febrile summer illness that led to paralytic sequelae. TV news included videos of the iron lung wards in hospitals across the country. Medical providers felt powerless, only able to give nonspecific preventive advice. There was no specific antiviral (there still isn’t) and vaccines seemed a long way off.

Then came the news that Dr. Jonas Salk’s group had gotten an inactivated polio vaccine (IPV) approved for general use in 1955. Families were excited to have their children vaccinated. Paralytic polio cases dropped like a rock from approximately 22,000/year in 1952 to approximately 2,200 in 1956. A surge to near 6,000 cases in 1959 led to Dr. Albert Sabin’s oral polio vaccine (OPV), which supplanted IPV in 1961. OPV had the advantages of: 1) Inducing mucosal as well as serum antibodies, 2) more durable responses, and 3) immunity in unvaccinated persons exposed to vaccine virus that had been shed in stools into wastewater and rivers.

By 1964, polio had nearly disappeared. The last wild-type indigenous U.S. case was in 1979. By 1994, all the Americas were declared polio free. Because the only U.S. paralytic polio cases thereafter were foreign imports or were associated with oral vaccine strains (so-called vaccine-associated paralytic polio [VAPP]), OPV was replaced by an enhanced IPV in 2000 to prevent further VAPP.

Polio facts: Polio is asymptomatic in about 70% of infections. Among the 30% with symptoms, paralysis occurs infrequently, with the overall rate of paralytic infections being 0.5% (rate varies by virus type with type 3 having the highest rate).¹ Why then was the world so afraid of polio? If every person in a U.S. birth cohort (about 3.7 million) was unvaccinated and became infected with poliovirus, more than 18,000 would get paralytic polio and almost 1,300 would die. Of note, adults have a higher chance of paralytic polio after infection than children.

Concerns in 2022: Persons vaccinated with at least three doses of either IPV or OPV have historically been protected from paralytic polio (99% protection). But are we sure that the United States remains protected against polio after 2 decades of IPV being the only vaccine? Polio could be reintroduced at any time to the United States from countries with reported cases that likely arose because of low vaccination rates related to war, famine, or political upheavals (Malawi, Mozambique, Nigeria, Pakistan, and Afghanistan).² The proof? The recent confirmed New York case.

International efforts resulted in global eradication of two polio wild-types viruses (type 2 in 2015 and type 3 in 2019). Nevertheless, vaccine-derived, virulent polio virus (VDPV) type 2 and VDPV-3 still circulate in some areas, particularly Africa (VDPV-2) and Israel (VDPV-3). The above-mentioned U.S. case is an unvaccinated adult traveler who went to an area where VDPV-2 circulates and developed disease after returning home.³ So, it was not an indigenous reappearance in the United States and it was not a breakthrough case in a vaccinated person. But it is sobering to realize that all who are unvaccinated remain at risk for paralytic polio in 2022, particularly because vaccination rates declined nearly everywhere during the initial COVID-19 pandemic. We are still catching up, with vaccination rates under 50% in some ZIP codes.⁴

Are VDPVs circulating in some parts of the United States? Interestingly, wastewater surveillance programs may be the most economical and practical way to perform polio surveillance. Such a program detected polio virus in London wastewater in June 2022.⁵ New York has recently detected polio in wastewater during testing begun because of the recent case.⁶

Good news: For paralytic polio, seropositivity at any titer indicates protection, so U.S. serosurveillance data would also be informative. How durable is polio protection in the IPV era? Available data suggest that even though we have used only IPV these past 20 years, seropositivity rates among vaccinees with at least three doses of either IPV or OPV should persist for decades and likely for life. Even before polio became a concern this year, the Centers for Disease Control and Prevention, being proactive, wanted to ensure that the enhanced IPV was producing durable immunity and that persons of all ages remained seropositive to the three polio virus types over 10 years after discontinuing OPV use in 2012.

The CDC collaborated with investigators in Kansas City, Mo., to evaluate titers and seropositivity to all three types in a 2- to 85-year-old otherwise healthy cohort with demographics that mirrored the 2010 census for the Kansas City region, which in turn mirrored the national 2021 census data.⁷ There were approximately 100 persons in each age cohort, with 200 below age 11 years (the cohort that had received only IPV). Serology was performed at the CDC.

Overall seropositivity rates were high, but lower for type 3 (83.3%) and type 2 (90.7%) than type 1 (94.4%). Of note, most of those seronegative for one or more types were among 2- to 3-year-olds who had not completed their full IPV series, with most seronegative results being against polio types 1 and 3. Further, five, who were confirmed as having received no polio vaccine, were seronegative for all three types. Two with no available vaccine records (over 18 years old) were also seronegative for all three types.

So, regardless of the era in which one got polio vaccine, vaccine protection appears to persist indefinitely after three doses. Even 80-year-olds were still seropositive if they had three doses. We can confidently reassure our patients that the vaccine still works; the persons who need to fear polio in 2022 are those who are not vaccinated or have had fewer than three doses, particularly if they travel to areas of persistent polio. Wild type 1 virus persists in a few countries as does VDPV type 2 and VDPV type 3. Importantly, wild type 2 and wild type 3 (with the lowest seropositivity in 2012 study) have been eliminated globally so the only circulating type 2 and type 3 polio virus is VDPV in a few countries. Travel to these countries warrants review of polio vaccine records and CDC or WHO current recommendations for travelers to those countries.
 

Dr. Harrison is a professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. Email him at pdnews@mdedge.com.

References

1. Poliomyelitis. World Health Organization fact sheet, 2022 Jul 4..

2. Franco-Paredes C et al. Lancet Infect Dis. 2022 Aug 16. doi: 10.1016/S1473-3099(22)00548-5.

3. Link-Gelles R et al. MMWR Morb Mortal Wkly Rep. 2022 Aug 19;71(33):1065-8.

4. “Polio vaccination rate for 2-year-olds is as low as 37% in parts of N.Y. county where paralysis case was found,” NBC News, Erika Edwards, 2022 Aug 16. 5. Vaccine-derived poliovirus type 2 (VDPV2) detected in environmental samples in London. Polioeradication.org. 2022 Jun 22.

6. “NYSDOH and NYCDOHMH wastewater monitoring identifies polio in New York City and urges unvaccinated New Yorkers to get vaccinated now,” nyc.gov. 2022 Aug 12.

7. Wallace GS et al. Hum Vaccin Immunother. 2017;13(4):776-83.

Key clinical point: Methotrexate dosage may be tapered from targeted therapy in patients with controlled rheumatoid arthritis (RA) but with a low risk for not being able to sustain remission for up to 18 months.

Major finding: The ability to sustain remission for up to 18 months was 10% lower in patients with RA who tapered vs did not taper methotrexate from targeted therapy (risk ratio 0.90; 95% CI 0.84-0.97).

Study details: This was a systematic review and meta-analysis of 10 studies including 2000 patients with early or established RA who received any targeted therapy in combination with methotrexate and eventually tapered their methotrexate dosage.

Disclosures: This study was supported by the Hospital for Special Surgery, New York. Some authors reported receiving grants, honoraria or consulting fees, or owning stocks in various sources.

Source: Meng CF et al. Can patients with controlled rheumatoid arthritis taper methotrexate from targeted therapy and sustain remission? A systematic review and meta-analysis. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220152

Key clinical point: Methotrexate dosage may be tapered from targeted therapy in patients with controlled rheumatoid arthritis (RA) but with a low risk for not being able to sustain remission for up to 18 months.

Major finding: The ability to sustain remission for up to 18 months was 10% lower in patients with RA who tapered vs did not taper methotrexate from targeted therapy (risk ratio 0.90; 95% CI 0.84-0.97).

Study details: This was a systematic review and meta-analysis of 10 studies including 2000 patients with early or established RA who received any targeted therapy in combination with methotrexate and eventually tapered their methotrexate dosage.

Disclosures: This study was supported by the Hospital for Special Surgery, New York. Some authors reported receiving grants, honoraria or consulting fees, or owning stocks in various sources.

Source: Meng CF et al. Can patients with controlled rheumatoid arthritis taper methotrexate from targeted therapy and sustain remission? A systematic review and meta-analysis. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220152

Key clinical point: Methotrexate dosage may be tapered from targeted therapy in patients with controlled rheumatoid arthritis (RA) but with a low risk for not being able to sustain remission for up to 18 months.

Major finding: The ability to sustain remission for up to 18 months was 10% lower in patients with RA who tapered vs did not taper methotrexate from targeted therapy (risk ratio 0.90; 95% CI 0.84-0.97).

Study details: This was a systematic review and meta-analysis of 10 studies including 2000 patients with early or established RA who received any targeted therapy in combination with methotrexate and eventually tapered their methotrexate dosage.

Disclosures: This study was supported by the Hospital for Special Surgery, New York. Some authors reported receiving grants, honoraria or consulting fees, or owning stocks in various sources.

Source: Meng CF et al. Can patients with controlled rheumatoid arthritis taper methotrexate from targeted therapy and sustain remission? A systematic review and meta-analysis. J Rheumatol. 2022 (Aug 15). Doi: 10.3899/jrheum.220152

Key clinical point: Real-world analysis demonstrated a higher efficacy of non-tumor necrosis factor inhibitors (non-TNFi) vs TNFi and Janus kinase inhibitors (JAKi) vs biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), along with a higher efficacy of adalimumab, etanercept, and golimumab vs infliximab within TNFi.

Major finding: Efficacies of TNFi vs non-TNFi drugs (risk ratio [RR] 0.88; P < .01) and bDMARD vs JAKi (RR 0.86; P < .01) were lower. Among TNFi, adalimumab, etanercept, and golimumab were 19.0% more effective than infliximab (RR 1.19; P < .01).

Study details: This was a systematic review and meta-analysis of 21 population-based, prospective, and retrospective cohort studies including 182,098 patients with RA.

Disclosures: This study was supported by the Secretariat of Science, Technology, Innovation, and Strategic Inputs of the Ministry of Health, Brazil, and the Oswaldo Cruz Foundation, Fiocruz. The authors declared no conflicts of interest.

Source: de Castro CT et al. Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis. Front Pharmacol. 2022;13:927179  (Aug 11). Doi: 10.3389/fphar.2022.927179

Key clinical point: Real-world analysis demonstrated a higher efficacy of non-tumor necrosis factor inhibitors (non-TNFi) vs TNFi and Janus kinase inhibitors (JAKi) vs biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), along with a higher efficacy of adalimumab, etanercept, and golimumab vs infliximab within TNFi.

Major finding: Efficacies of TNFi vs non-TNFi drugs (risk ratio [RR] 0.88; P < .01) and bDMARD vs JAKi (RR 0.86; P < .01) were lower. Among TNFi, adalimumab, etanercept, and golimumab were 19.0% more effective than infliximab (RR 1.19; P < .01).

Study details: This was a systematic review and meta-analysis of 21 population-based, prospective, and retrospective cohort studies including 182,098 patients with RA.

Disclosures: This study was supported by the Secretariat of Science, Technology, Innovation, and Strategic Inputs of the Ministry of Health, Brazil, and the Oswaldo Cruz Foundation, Fiocruz. The authors declared no conflicts of interest.

Source: de Castro CT et al. Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis. Front Pharmacol. 2022;13:927179  (Aug 11). Doi: 10.3389/fphar.2022.927179

Key clinical point: Real-world analysis demonstrated a higher efficacy of non-tumor necrosis factor inhibitors (non-TNFi) vs TNFi and Janus kinase inhibitors (JAKi) vs biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), along with a higher efficacy of adalimumab, etanercept, and golimumab vs infliximab within TNFi.

Major finding: Efficacies of TNFi vs non-TNFi drugs (risk ratio [RR] 0.88; P < .01) and bDMARD vs JAKi (RR 0.86; P < .01) were lower. Among TNFi, adalimumab, etanercept, and golimumab were 19.0% more effective than infliximab (RR 1.19; P < .01).

Study details: This was a systematic review and meta-analysis of 21 population-based, prospective, and retrospective cohort studies including 182,098 patients with RA.

Disclosures: This study was supported by the Secretariat of Science, Technology, Innovation, and Strategic Inputs of the Ministry of Health, Brazil, and the Oswaldo Cruz Foundation, Fiocruz. The authors declared no conflicts of interest.

Source: de Castro CT et al. Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis. Front Pharmacol. 2022;13:927179  (Aug 11). Doi: 10.3389/fphar.2022.927179

Key clinical point: Patients with rheumatoid arthritis (RA) who received biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) were at a reduced risk for incident dementia compared with those who received conventional synthetic disease-modifying antirheumatic drugs (csDMARD) alone.

Major finding: Compared with only csDMARD use, the use of b/tsDMARD was associated with a 19% lower risk for incident dementia (adjusted hazard ratio [aHR] 0.81; 95% CI 0.76-0.87), with findings being similar for all b/tsDMARD categories: tumor necrosis factor inhibitors (TNFi; aHR 0.86; 95% CI 0.80-0.93), non-TNFi (aHR 0.76; 95% CI 0.70-0.83), and tsDMARD (aHR 0.69; 95% CI 0.53-0.90).

Study details: This was a retrospective cohort study including 141,326 patients aged ≥40 years with RA who received b/tsDMARD with or without csDMARD or csDMARD only.

Disclosures: This study was supported by a BIGDATA core grant from the US National Institutes of Health. Some authors reported receiving research support, grants, or consulting fees from various sources.

Source: Sattui SE et al. Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs - Analysis of a national claims database. Semin Arthritis Rheum. 2022 (Aug 17). Doi: 10.1016/j.semarthrit.2022.152083

Key clinical point: Patients with rheumatoid arthritis (RA) who received biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) were at a reduced risk for incident dementia compared with those who received conventional synthetic disease-modifying antirheumatic drugs (csDMARD) alone.

Major finding: Compared with only csDMARD use, the use of b/tsDMARD was associated with a 19% lower risk for incident dementia (adjusted hazard ratio [aHR] 0.81; 95% CI 0.76-0.87), with findings being similar for all b/tsDMARD categories: tumor necrosis factor inhibitors (TNFi; aHR 0.86; 95% CI 0.80-0.93), non-TNFi (aHR 0.76; 95% CI 0.70-0.83), and tsDMARD (aHR 0.69; 95% CI 0.53-0.90).

Study details: This was a retrospective cohort study including 141,326 patients aged ≥40 years with RA who received b/tsDMARD with or without csDMARD or csDMARD only.

Disclosures: This study was supported by a BIGDATA core grant from the US National Institutes of Health. Some authors reported receiving research support, grants, or consulting fees from various sources.

Source: Sattui SE et al. Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs - Analysis of a national claims database. Semin Arthritis Rheum. 2022 (Aug 17). Doi: 10.1016/j.semarthrit.2022.152083

Key clinical point: Patients with rheumatoid arthritis (RA) who received biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) were at a reduced risk for incident dementia compared with those who received conventional synthetic disease-modifying antirheumatic drugs (csDMARD) alone.

Major finding: Compared with only csDMARD use, the use of b/tsDMARD was associated with a 19% lower risk for incident dementia (adjusted hazard ratio [aHR] 0.81; 95% CI 0.76-0.87), with findings being similar for all b/tsDMARD categories: tumor necrosis factor inhibitors (TNFi; aHR 0.86; 95% CI 0.80-0.93), non-TNFi (aHR 0.76; 95% CI 0.70-0.83), and tsDMARD (aHR 0.69; 95% CI 0.53-0.90).

Study details: This was a retrospective cohort study including 141,326 patients aged ≥40 years with RA who received b/tsDMARD with or without csDMARD or csDMARD only.

Disclosures: This study was supported by a BIGDATA core grant from the US National Institutes of Health. Some authors reported receiving research support, grants, or consulting fees from various sources.

Source: Sattui SE et al. Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs - Analysis of a national claims database. Semin Arthritis Rheum. 2022 (Aug 17). Doi: 10.1016/j.semarthrit.2022.152083

Key clinical point: Iguratimod as monotherapy or in combination with methotrexate showed clear benefits over methotrexate in improving disease activity in patients with rheumatoid arthritis (RA) along with a comparable safety profile.

Major finding: Compared with methotrexate monotherapy, iguratimod monotherapy and iguratimod+methotrexate therapy were associated with more effective improvements in the American College of Rheumatology 20% improvement response rate (risk ratio [RR] 1.15; P  =  .004; and RR 1.24; P < .00001, respectively) and 28-joint Disease Activity Score based on erythrocyte sedimentation rate (mean difference [MD] −0.15; P  =  .01; and MD −1.43; P < .00001, respectively) with a similar incidence of adverse events.

Study details: Findings are from a systematic review and meta-analysis of 38 randomized controlled trials including 4302 patients with RA who received iguratimod alone, iguratimod with methotrexate, methotrexate alone, or methotrexate with leflunomide or hydroxychloroquine or tripterygium glycosides.

Disclosures: This study was supported by the National Youth Science Foundation of China and Research Fund of Hunan Province Education Department. The authors declared no conflicts of interest.

Source: Ouyang D et al. Effectiveness and safety of iguratimod monotherapy or combined with methotrexate in treating rheumatoid arthritis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:911810 (Aug 5). Doi: 10.3389/fphar.2022.911810

Key clinical point: Iguratimod as monotherapy or in combination with methotrexate showed clear benefits over methotrexate in improving disease activity in patients with rheumatoid arthritis (RA) along with a comparable safety profile.

Major finding: Compared with methotrexate monotherapy, iguratimod monotherapy and iguratimod+methotrexate therapy were associated with more effective improvements in the American College of Rheumatology 20% improvement response rate (risk ratio [RR] 1.15; P  =  .004; and RR 1.24; P < .00001, respectively) and 28-joint Disease Activity Score based on erythrocyte sedimentation rate (mean difference [MD] −0.15; P  =  .01; and MD −1.43; P < .00001, respectively) with a similar incidence of adverse events.

Study details: Findings are from a systematic review and meta-analysis of 38 randomized controlled trials including 4302 patients with RA who received iguratimod alone, iguratimod with methotrexate, methotrexate alone, or methotrexate with leflunomide or hydroxychloroquine or tripterygium glycosides.

Disclosures: This study was supported by the National Youth Science Foundation of China and Research Fund of Hunan Province Education Department. The authors declared no conflicts of interest.

Source: Ouyang D et al. Effectiveness and safety of iguratimod monotherapy or combined with methotrexate in treating rheumatoid arthritis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:911810 (Aug 5). Doi: 10.3389/fphar.2022.911810

Key clinical point: Iguratimod as monotherapy or in combination with methotrexate showed clear benefits over methotrexate in improving disease activity in patients with rheumatoid arthritis (RA) along with a comparable safety profile.

Major finding: Compared with methotrexate monotherapy, iguratimod monotherapy and iguratimod+methotrexate therapy were associated with more effective improvements in the American College of Rheumatology 20% improvement response rate (risk ratio [RR] 1.15; P  =  .004; and RR 1.24; P < .00001, respectively) and 28-joint Disease Activity Score based on erythrocyte sedimentation rate (mean difference [MD] −0.15; P  =  .01; and MD −1.43; P < .00001, respectively) with a similar incidence of adverse events.

Study details: Findings are from a systematic review and meta-analysis of 38 randomized controlled trials including 4302 patients with RA who received iguratimod alone, iguratimod with methotrexate, methotrexate alone, or methotrexate with leflunomide or hydroxychloroquine or tripterygium glycosides.

Disclosures: This study was supported by the National Youth Science Foundation of China and Research Fund of Hunan Province Education Department. The authors declared no conflicts of interest.

Source: Ouyang D et al. Effectiveness and safety of iguratimod monotherapy or combined with methotrexate in treating rheumatoid arthritis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:911810 (Aug 5). Doi: 10.3389/fphar.2022.911810

Key clinical point: Individual tapering of disease-modifying antirheumatic drugs (DMARD) might be feasible in patients with rheumatoid arthritis (RA) in sustained remission for more than 6 months.

Major finding: The risks for flare (adjusted hazard ratio [aHR] 0.88; 95% CI 0.59-1.30) and loss of remission (aHR 1.04; 95% CI 0.73-1.49) were not significantly different among patients who tapered vs continued DMARD. The clinical disease activity index showed a minor and nonsignificant increase at 12 months in patients who tapered vs continued DMARD (1.80 vs 0.91 units; P  =  .076).

Study details: Findings are from an analysis of a prospective cohort of 437 patients with RA in sustained remission for ≥6 months who either tapered or continued DMARD.

Disclosures: This study was supported by the Federal Joint Committee, Germany. All authors reported receiving grants from the Federal Joint Committee. E Edelmann reported receiving personal fees from various sources. F Verheyen contributed as an employee of Techniker Krankenkasse.

Source: Birkner B et al. Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting. Rheumatology (Oxford). 2022 (Aug 18). Doi:  10.1093/rheumatology/keac472

Key clinical point: Individual tapering of disease-modifying antirheumatic drugs (DMARD) might be feasible in patients with rheumatoid arthritis (RA) in sustained remission for more than 6 months.

Major finding: The risks for flare (adjusted hazard ratio [aHR] 0.88; 95% CI 0.59-1.30) and loss of remission (aHR 1.04; 95% CI 0.73-1.49) were not significantly different among patients who tapered vs continued DMARD. The clinical disease activity index showed a minor and nonsignificant increase at 12 months in patients who tapered vs continued DMARD (1.80 vs 0.91 units; P  =  .076).

Study details: Findings are from an analysis of a prospective cohort of 437 patients with RA in sustained remission for ≥6 months who either tapered or continued DMARD.

Disclosures: This study was supported by the Federal Joint Committee, Germany. All authors reported receiving grants from the Federal Joint Committee. E Edelmann reported receiving personal fees from various sources. F Verheyen contributed as an employee of Techniker Krankenkasse.

Source: Birkner B et al. Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting. Rheumatology (Oxford). 2022 (Aug 18). Doi:  10.1093/rheumatology/keac472

Key clinical point: Individual tapering of disease-modifying antirheumatic drugs (DMARD) might be feasible in patients with rheumatoid arthritis (RA) in sustained remission for more than 6 months.

Major finding: The risks for flare (adjusted hazard ratio [aHR] 0.88; 95% CI 0.59-1.30) and loss of remission (aHR 1.04; 95% CI 0.73-1.49) were not significantly different among patients who tapered vs continued DMARD. The clinical disease activity index showed a minor and nonsignificant increase at 12 months in patients who tapered vs continued DMARD (1.80 vs 0.91 units; P  =  .076).

Study details: Findings are from an analysis of a prospective cohort of 437 patients with RA in sustained remission for ≥6 months who either tapered or continued DMARD.

Disclosures: This study was supported by the Federal Joint Committee, Germany. All authors reported receiving grants from the Federal Joint Committee. E Edelmann reported receiving personal fees from various sources. F Verheyen contributed as an employee of Techniker Krankenkasse.

Source: Birkner B et al. Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting. Rheumatology (Oxford). 2022 (Aug 18). Doi:  10.1093/rheumatology/keac472

Key clinical point: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (methotrexate-IR) who initiated upadacitinib vs adalimumab spent a longer time in improved disease states and reported faster achievement of treatment targets.

Major finding: Patients initially receiving upadacitinib vs adalimumab spent 19% vs 14% of the time over 48 weeks in clinical disease activity index remission (nominal P  =  .012) and achieved the 28-joint disease activity score using C-reactive protein of <2.6/≤3.2 approximately 6-8 weeks (median time) earlier.

Study details: Findings are from a post hoc analysis including patients with RA and methotrexate-IR from the phase 3 SELECT-COMPARE trial who were randomly assigned to receive upadacitinib (n = 651) or adalimumab (n = 327) with background methotrexate.

Disclosures: The trial was funded by AbbVie, Inc. Five authors declared being employees of and may own stocks or options in AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mysler E et al. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: Post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2022 (Aug 26). Doi:  10.1093/rheumatology/keac477

Key clinical point: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (methotrexate-IR) who initiated upadacitinib vs adalimumab spent a longer time in improved disease states and reported faster achievement of treatment targets.

Major finding: Patients initially receiving upadacitinib vs adalimumab spent 19% vs 14% of the time over 48 weeks in clinical disease activity index remission (nominal P  =  .012) and achieved the 28-joint disease activity score using C-reactive protein of <2.6/≤3.2 approximately 6-8 weeks (median time) earlier.

Study details: Findings are from a post hoc analysis including patients with RA and methotrexate-IR from the phase 3 SELECT-COMPARE trial who were randomly assigned to receive upadacitinib (n = 651) or adalimumab (n = 327) with background methotrexate.

Disclosures: The trial was funded by AbbVie, Inc. Five authors declared being employees of and may own stocks or options in AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mysler E et al. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: Post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2022 (Aug 26). Doi:  10.1093/rheumatology/keac477

Key clinical point: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (methotrexate-IR) who initiated upadacitinib vs adalimumab spent a longer time in improved disease states and reported faster achievement of treatment targets.

Major finding: Patients initially receiving upadacitinib vs adalimumab spent 19% vs 14% of the time over 48 weeks in clinical disease activity index remission (nominal P  =  .012) and achieved the 28-joint disease activity score using C-reactive protein of <2.6/≤3.2 approximately 6-8 weeks (median time) earlier.

Study details: Findings are from a post hoc analysis including patients with RA and methotrexate-IR from the phase 3 SELECT-COMPARE trial who were randomly assigned to receive upadacitinib (n = 651) or adalimumab (n = 327) with background methotrexate.

Disclosures: The trial was funded by AbbVie, Inc. Five authors declared being employees of and may own stocks or options in AbbVie. The other authors reported ties with various sources, including AbbVie.

Source: Mysler E et al. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: Post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2022 (Aug 26). Doi:  10.1093/rheumatology/keac477

Key clinical point: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) were at an increased risk for mortality, with age, chronic obstructive pulmonary disease (COPD), diabetes mellitus with end-organ damage (DM-EOD), and corticosteroid dose being the major risk factors.

Major finding: Risk for mortality was higher in patients with RA-ILD vs RA without ILD (adjusted hazard ratio [aHR] 4.38; 95% CI 2.03-9.43). Age at ILD diagnosis (aHR 1.05; P < .001), comorbidities, such as COPD (aHR 2.12; P  =  .005) and DM-EOD (aHR 33.85; P  =  .002), and average daily prednisolone dose (aHR 1.09; P < .001) were associated with an increased risk for mortality in patients with RA-ILD.

Study details: Findings are from a population-based cohort study including patients with RA-ILD (n = 214) and RA without ILD (n = 30,882) who were propensity-matched (1:1) for selected comorbidities.

Disclosures: This study did not receive any funding. No conflicts of interest were declared.

Source: Ng K-H et al. Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: A nationwide, population-based cohort study in Taiwan. RMD Open. 2022;8(2):e002343 (Aug 22). Doi: 10.1136/rmdopen-2022-002343

Key clinical point: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) were at an increased risk for mortality, with age, chronic obstructive pulmonary disease (COPD), diabetes mellitus with end-organ damage (DM-EOD), and corticosteroid dose being the major risk factors.

Major finding: Risk for mortality was higher in patients with RA-ILD vs RA without ILD (adjusted hazard ratio [aHR] 4.38; 95% CI 2.03-9.43). Age at ILD diagnosis (aHR 1.05; P < .001), comorbidities, such as COPD (aHR 2.12; P  =  .005) and DM-EOD (aHR 33.85; P  =  .002), and average daily prednisolone dose (aHR 1.09; P < .001) were associated with an increased risk for mortality in patients with RA-ILD.

Study details: Findings are from a population-based cohort study including patients with RA-ILD (n = 214) and RA without ILD (n = 30,882) who were propensity-matched (1:1) for selected comorbidities.

Disclosures: This study did not receive any funding. No conflicts of interest were declared.

Source: Ng K-H et al. Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: A nationwide, population-based cohort study in Taiwan. RMD Open. 2022;8(2):e002343 (Aug 22). Doi: 10.1136/rmdopen-2022-002343

Key clinical point: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) were at an increased risk for mortality, with age, chronic obstructive pulmonary disease (COPD), diabetes mellitus with end-organ damage (DM-EOD), and corticosteroid dose being the major risk factors.

Major finding: Risk for mortality was higher in patients with RA-ILD vs RA without ILD (adjusted hazard ratio [aHR] 4.38; 95% CI 2.03-9.43). Age at ILD diagnosis (aHR 1.05; P < .001), comorbidities, such as COPD (aHR 2.12; P  =  .005) and DM-EOD (aHR 33.85; P  =  .002), and average daily prednisolone dose (aHR 1.09; P < .001) were associated with an increased risk for mortality in patients with RA-ILD.

Study details: Findings are from a population-based cohort study including patients with RA-ILD (n = 214) and RA without ILD (n = 30,882) who were propensity-matched (1:1) for selected comorbidities.

Disclosures: This study did not receive any funding. No conflicts of interest were declared.

Source: Ng K-H et al. Analysis of risk factors of mortality in rheumatoid arthritis patients with interstitial lung disease: A nationwide, population-based cohort study in Taiwan. RMD Open. 2022;8(2):e002343 (Aug 22). Doi: 10.1136/rmdopen-2022-002343

Key clinical point: Ultra-low dosing and repeated COVID-19 vaccination as late as possible after the latest rituximab infusion seems to be the best vaccination strategy in rituximab-treated patients with rheumatoid arthritis (RA).

Major finding: Humoral response after the third COVID-19 vaccination was numerically higher with 200 vs 1000 mg as the latest rituximab dose for the first vaccination (38% vs 15%; P  =  .06), with a trend toward improved response observed with a longer time between rituximab infusion and vaccination (odds ratio 1.16 per month increased time; P  =  .10). Overall, the humoral response persisted in 96% of patients, with response being persistent in 89% of patients despite intercurrent rituximab infusion.

Study details: Findings are from a follow-up study of the RTX-COVAC cohort including 121 rituximab-treated patients with RA who received a third COVID-19 vaccination.

Disclosures: This study did not receive any funding. AA den Broeder reported receiving grants outside the submitted work from various sources. The other authors declared no conflicts of interest.

Source: van der Togt CJT et al. Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Aug 24). Doi: 10.1093/rheumatology/keac486

Key clinical point: Ultra-low dosing and repeated COVID-19 vaccination as late as possible after the latest rituximab infusion seems to be the best vaccination strategy in rituximab-treated patients with rheumatoid arthritis (RA).

Major finding: Humoral response after the third COVID-19 vaccination was numerically higher with 200 vs 1000 mg as the latest rituximab dose for the first vaccination (38% vs 15%; P  =  .06), with a trend toward improved response observed with a longer time between rituximab infusion and vaccination (odds ratio 1.16 per month increased time; P  =  .10). Overall, the humoral response persisted in 96% of patients, with response being persistent in 89% of patients despite intercurrent rituximab infusion.

Study details: Findings are from a follow-up study of the RTX-COVAC cohort including 121 rituximab-treated patients with RA who received a third COVID-19 vaccination.

Disclosures: This study did not receive any funding. AA den Broeder reported receiving grants outside the submitted work from various sources. The other authors declared no conflicts of interest.

Source: van der Togt CJT et al. Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Aug 24). Doi: 10.1093/rheumatology/keac486

Key clinical point: Ultra-low dosing and repeated COVID-19 vaccination as late as possible after the latest rituximab infusion seems to be the best vaccination strategy in rituximab-treated patients with rheumatoid arthritis (RA).

Major finding: Humoral response after the third COVID-19 vaccination was numerically higher with 200 vs 1000 mg as the latest rituximab dose for the first vaccination (38% vs 15%; P  =  .06), with a trend toward improved response observed with a longer time between rituximab infusion and vaccination (odds ratio 1.16 per month increased time; P  =  .10). Overall, the humoral response persisted in 96% of patients, with response being persistent in 89% of patients despite intercurrent rituximab infusion.

Study details: Findings are from a follow-up study of the RTX-COVAC cohort including 121 rituximab-treated patients with RA who received a third COVID-19 vaccination.

Disclosures: This study did not receive any funding. AA den Broeder reported receiving grants outside the submitted work from various sources. The other authors declared no conflicts of interest.

Source: van der Togt CJT et al. Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Aug 24). Doi: 10.1093/rheumatology/keac486

Feelings of detachment following a traumatic event are a marker of more severe psychiatric outcomes, including depression and anxiety, new research suggests.

The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.

“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.

The study was published in the American Journal of Psychiatry.
 

Underdiagnosed

Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.

Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.

“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.

Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.

About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
 

Brain imaging data

A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.

In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.

About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.

After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.

The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.

Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.

“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
 

More pain, depression, anxiety

Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.

“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.

Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.

Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.

She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.

“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”

Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.

A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.

Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
 

An important investigation

In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.

Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.

The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.

Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.

However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”

The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.

The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.

A version of this article first appeared on Medscape.com.

Feelings of detachment following a traumatic event are a marker of more severe psychiatric outcomes, including depression and anxiety, new research suggests.

The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.

“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.

The study was published in the American Journal of Psychiatry.
 

Underdiagnosed

Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.

Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.

“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.

Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.

About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
 

Brain imaging data

A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.

In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.

About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.

After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.

The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.

Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.

“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
 

More pain, depression, anxiety

Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.

“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.

Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.

Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.

She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.

“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”

Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.

A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.

Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
 

An important investigation

In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.

Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.

The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.

Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.

However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”

The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.

The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.

A version of this article first appeared on Medscape.com.

Feelings of detachment following a traumatic event are a marker of more severe psychiatric outcomes, including depression and anxiety, new research suggests.

The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.

“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.

The study was published in the American Journal of Psychiatry.
 

Underdiagnosed

Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.

Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.

“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.

Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.

About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
 

Brain imaging data

A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.

In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.

About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.

After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.

The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.

Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.

“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
 

More pain, depression, anxiety

Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.

“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.

Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.

Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.

She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.

“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”

Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.

A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.

Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
 

An important investigation

In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.

Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.

The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.

Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.

However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”

The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.

The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.

A version of this article first appeared on Medscape.com.