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Foreword: VA Research and COVID-19
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Meta-analysis evaluates conventional treatments for RA
Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.
Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.
Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.
Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.
Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950
Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.
Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.
Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.
Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.
Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950
Key clinical point: Methotrexate remains the anchor untargeted conventional treatment for rheumatoid arthritis (RA); however, several alternatives are now available in case of suboptimal outcomes or unacceptable adverse events with methotrexate.
Major finding: Methotrexate reduced the imputed tender joint count (TJCi) by 5.18 joints (95% credible interval [CrI] 4.07-6.28 joints) compared with placebo. Cyclophosphamide fared better than methotrexate in terms of TJCi reduction (6.08 joints; 95% CrI 0.44-11.66 joints), but glucocorticoids (−2.54 joints; 95% CrI −5.16 to 0.08 joints) and the remaining drugs showed similar or lower reductions in the TJCi.
Study details: Findings are from a network meta-analysis of 29 interventions investigated in 132 randomized clinical trials including 13,260 patients with RA who were randomly assigned to receive conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids, placebo, or a pharmacologic non-disease-modifying comparator.
Disclosures: This study was funded by grants from the Danish Regions Medicine Fund and other sources. The authors declared no conflicts of interest.
Source: Guski LS et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: A network meta-analysis. JAMA Netw Open. 2023;6(10):e2335950 (Oct 6). doi: 10.1001/jamanetworkopen.2023.35950
Cardiovascular risk linked with JAKi and bDMARD use in RA
Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.
Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P = .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).
Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.
Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.
Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531
Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.
Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P = .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).
Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.
Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.
Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531
Key clinical point: The risk for cardiovascular events was similar with Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA), although the risk may be slightly higher in elderly patients.
Major finding: JAKi vs bDMARD were not associated with a significantly different risk for cardiovascular events (adjusted incidence rate ratio [aIRR] 1.01; P = .965), but with a trend for a higher cardiovascular risk among patients > 65 years old (aIRR 1.24; 95% CI 0.80-1.91) and a lower risk among patients < 65 years old (aIRR 0.70; 95% CI 0.39-1.28).
Study details: Findings are from a retrospective inception cohort study including 15,191 patients with RA from the IQVIA’s Real-World Data Longitudinal Prescription database who had started a new bDMARD or JAKi.
Disclosures: This study was supported by an unrestricted educational grant from Pfizer BV. Two authors declared receiving past grants to the institution from various sources, including Pfizer. The other authors declared no conflicts of interest.
Source: Popa CD et al. Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population. Rheumatology (Oxford). 2023 (Oct 5). doi: 10.1093/rheumatology/kead531
Deciphering difficult-to-treat RA in patients receiving b/tsDMARD
Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.
Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P = .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P = .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P = .008), sulfasalazine (aOR 0.59; P = .003), and leflunomide (aOR 0.67; P = .013) were associated with D2T RA.
Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.
Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.
Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w
Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.
Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P = .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P = .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P = .008), sulfasalazine (aOR 0.59; P = .003), and leflunomide (aOR 0.67; P = .013) were associated with D2T RA.
Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.
Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.
Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w
Key clinical point: Patients with difficult-to-treat (D2T) rheumatoid arthritis (RA) had a higher disease activity despite treatment with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) and demonstrated higher withdrawal rates due to inefficacy.
Major finding: Patients with vs without D2T RA had a higher Simplified Disease Activity Index (SDAI; P = .003) and higher withdrawal rates for b/tsDMARD due to inefficacy (P < .001). Higher SDAI (adjusted odds ratio [aOR] 1.06; P = .014), longer disease duration (aOR 1.06; P < .001), and lower prior use of methotrexate (aOR 0.44; P = .008), sulfasalazine (aOR 0.59; P = .003), and leflunomide (aOR 0.67; P = .013) were associated with D2T RA.
Study details: Findings are from a retrospective study including 2321 patients with RA from the Korean College of Rheumatology Biologics Registry who initiated or switched to b/tsDMARD, of which 271 patients had D2T RA.
Disclosures: This study was supported by a grant from the Yuhan Corporation, Seoul. The authors declared no conflicts of interest.
Source: Jung J-Y et al. Unveiling difficult-to-treat rheumatoid arthritis: Long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry. Arthritis Res Ther. 2023;25:174 (Sep 19). doi: 10.1186/s13075-023-03165-w
Differential joint-specific treatment response to tofacitinib and methotrexate in RA
Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.
Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).
Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).
Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.
Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1
Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.
Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).
Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).
Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.
Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1
Key clinical point: Methotrexate-naive patients with rheumatoid arthritis (RA) showed varied joint-specific clinical responses to tofacitinib and methotrexate monotherapies, with those receiving methotrexate demonstrating more radiographic progression in the foot joints despite improved clinical response.
Major finding: At 12 months, tofacitinib vs methotrexate improved the clinical response in most tender and swollen joints, except some foot joints. Methotrexate improved the clinical response in most foot joints; however, radiographic progression was significantly worse with methotrexate vs tofacitinib (P < .05).
Study details: Findings are from a post hoc analysis of the phase 3 ORAL Start trial including 956 methotrexate-naive patients with RA who were randomly assigned to receive monotherapy with 5 mg (n = 373) or 10 mg (n = 397) tofacitinib or methotrexate (n = 186).
Disclosures: This study was sponsored by Pfizer, Inc. Four authors declared being current or former employees or shareholders of Pfizer or Syneos Health. Some authors declared receiving grants, honoraria, or research funding or having other ties with various sources, including Pfizer.
Source: Ciurea A et al. Joint-level responses to tofacitinib and methotrexate: A post hoc analysis of data from ORAL Start. Arthritis Res Ther. 2023;25:185 (Sep 29). doi: 10.1186/s13075-023-03144-1
Risk factors for radiographic progression in bDMARD-treated RA
Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).
Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P = .033).
Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.
Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.
Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534
Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).
Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P = .033).
Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.
Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.
Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534
Key clinical point: Younger age, higher disease activity, prevalent erosions, and monotherapy were significant risk factors for the development of new bone erosions in biologic disease-modifying antirheumatic drug (bDMARD)-treated patients with rheumatoid arthritis (RA).
Major finding: Risk of developing new bone erosions increased with younger age (adjusted odds ratio [aOR] 0.970; P < .001), higher Disease Activity Scores for 28 Joints-C-Reactive Protein (aOR per point increase 5.349; P < .001), presence of erosions at baseline (aOR 7.820; P < .001), and conventional DMARD-naive status (aOR 2.068; P = .033).
Study details: Findings are from a retrospective analysis of prospectively collected data of 578 patients with RA who started bDMARD treatment.
Disclosures: This study did not receive any funding. G Adami, D Gatti, and M Rossini declared receiving personal fees or serving as a consultant or speaker for various sources. The other authors declared no conflicts of interest.
Source: Adami G et al. Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Ther Adv Musculoskelet Dis. 2023;15:1759720X231174534 (Sep 28). doi: 10.1177/1759720X231174534
Real-world effectiveness of T2T and routine care in abatacept-treated moderate-to-severe RA
Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).
Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P = .0263).
Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.
Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.
Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2
Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).
Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P = .0263).
Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.
Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.
Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2
Key clinical point: Abatacept improved disease activity in patients with moderate-to-severe rheumatoid arthritis (RA), with those managed with treat-to-target (T2T) approach being more likely to achieve low disease activity (LDA) compared with routine care (RC).
Major finding: In each treatment group, abatacept treatment led to early and sustained improvement in disease activity (P < .0001). However, the odds of achieving Clinical Disease Activity Index LDA were significantly higher with T2T vs RC approach (odds ratio 1.33; P = .0263).
Study details: Findings are from the 12-month prospective, randomized Abatacept Best Care trial including 284 patients with moderate-to-severely active RA who initiated abatacept as first- or second-line biologic therapy and were randomly assigned to the T2T (n = 130) or RC (n = 154) group.
Disclosures: This study was managed by JSS Medical Research, and the trial was funded by Bristol Myers Squibb (BMS). Three authors declared being employees of or holding stock or stock options in BMS or JSS Medical Research. Several authors declared ties with various sources, including BMS.
Source: Bessette L et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther. 2023;25:183 (Sep 28). doi: 10.1186/s13075-023-03151-2
Prevalence and risk factors for fibrotic progression in patients with RA-ILD
Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.
Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P = .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.
Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355
Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.
Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P = .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.
Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355
Key clinical point: Nearly half of the patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) showed radiographic progression of fibrosis, and the presence of diabetes mellitus, high disease activity, and advanced high-resolution computed tomography (HRCT) scores significantly increased the fibrotic progression risk.
Major finding: HRCT-based radiographic progression of fibrosis was observed in 51.0% of patients with RA-ILD, with diabetes mellitus (hazard ratio [HR] 2.47; P < .01), Disease Activity Scores in 28 Joints-Erythrocyte Sedimentation Rate > 5.1 (HR 2.32; P = .04), and baseline HRCT scores > 5 (HR 3.04; P < .01) being significant risk factors for fibrotic progression.
Study details: Findings are from a retrospective cohort study including 371 patients with RA, of which 32.3% had RA-ILD.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Chai D et al. Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease. Front Med (Lausanne). 2023;10:1265355 (Sep 22). doi: 10.3389/fmed.2023.1265355
Encouraging evidence to consider glucocorticoid tapering and discontinuation in RA
Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.
Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).
Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.
Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.
Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z
Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.
Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).
Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.
Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.
Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z
Key clinical point: The findings demonstrate the feasibility of glucocorticoid discontinuation in patients with long-standing rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) treated with tofacitinib, highlighting the steroid-sparing effect of tofacitinib.
Major finding: Overall, 30% and 40% of patients completely discontinued prednisone by weeks 12 and 24-48 of initiating tofacitinib, respectively. The median prednisone dose was reduced from 5 to 2.5 mg/day at week 12 (P < .00001), with nine patients further reducing the glucocorticoid dose to 1.25 mg/day from week 12 to week 48 (P < .00001).
Study details: This prospective, open-label, pilot study included 30 patients with moderate-to-severe RA and MTX-IR receiving a stable dose of glucocorticoids who initiated 5 mg tofacitinib twice daily, of which those who achieved at least a moderate European Alliance of Associations for Rheumatology response initiated glucocorticoid tapering until complete discontinuation.
Disclosures: This study was supported by a Pfizer Grant Award. FR Spinelli declared receiving a research grant from Pfizer. The other authors declared no conflicts of interest.
Source: Spinelli FR et al. Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib. Sci Rep. 2023;13:15537 (Sep 20). doi: 10.1038/s41598-023-42371-z
Microscopic colitis raises risk for incident RA
Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.
Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).
Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.
Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.
Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708
Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.
Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).
Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.
Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.
Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708
Key clinical point: Patients with microscopic colitis (MC) were at nearly 2-fold higher risk of developing rheumatoid arthritis (RA) compared with the general population, with a significant risk persisting up to 5 years after MC diagnosis.
Major finding: The risk for RA was significantly higher in patients with MC compared with matched reference individuals (adjusted hazard ratio [aHR] 1.83; 95% CI 1.39-2.41) and full siblings without MC (aHR 2.04; 95% CI 1.18-3.56). The risk was highest during the first year of follow-up (aHR 2.31; 95% CI 1.08-4.97) and remained significantly high up to 5 years after MC diagnosis (aHR 2.16; 95% CI 1.42-3.30).
Study details: Findings are from a population-based matched cohort study including 8179 patients with biopsy-verified MC, 36,400 matched reference individuals, and 8202 full siblings without MC.
Disclosures: This study was funded by Karolinska Institutet and other sources. Some authors declared serving as study coordinators or advisory board members for, receiving financial support from, and reporting agreements between various sources.
Source: Bergman D et al. Microscopic colitis and risk of incident rheumatoid arthritis: A nationwide population-based matched cohort study. Aliment Pharmacol Ther. 2023 (Sep 20). D+oi: 10.1111/apt.17708