Edward C Keystone1,2, Emmanouil Rampakakis3,4, Mohammad Movahedi3,4, Angela Cesta3,4, Melissa Stutz3,4, John S Sampalis3,4, Francois Nantel3,4, Karina Maslova3,4, Claire Bombardier3,4. 1. From The Rebecca MacDonald Centre for Arthritis, Mount Sinai Hospital; Toronto General Hospital Research Institute, University Health Network; Janssen Inc.; University of Toronto, Department of Medicine (DMO) and Institute of Health Policy, Management, and Evaluation (IHPME); Mount Sinai Hospital, Division of Rheumatology, Toronto, Ontario; JSS Medical Research Inc., Montreal, Quebec, Canada. Ed.Keystone@sinaihealthsystem.ca. 2. E.C. Keystone, MD, The Rebecca MacDonald Centre for Arthritis, Mount Sinai Hospital; E. Rampakakis, PhD, JSS Medical Research Inc.; M. Movahedi, MD, PhD, Toronto General Hospital Research Institute, University Health Network; A. Cesta, MSc, Toronto General Hospital Research Institute, University Health Network; M. Stutz, MSc, JSS Medical Research Inc.; J.S. Sampalis, PhD, JSS Medical Research Inc.; F. Nantel, PhD, Janssen Inc.; K. Maslova, PhD, Janssen Inc.; C. Bombardier, MD, Toronto General Hospital Research Institute, University Health Network, and University of Toronto, DMO and IHPME, and Mount Sinai Hospital, Division of Rheumatology. Ed.Keystone@sinaihealthsystem.ca. 3. From The Rebecca MacDonald Centre for Arthritis, Mount Sinai Hospital; Toronto General Hospital Research Institute, University Health Network; Janssen Inc.; University of Toronto, Department of Medicine (DMO) and Institute of Health Policy, Management, and Evaluation (IHPME); Mount Sinai Hospital, Division of Rheumatology, Toronto, Ontario; JSS Medical Research Inc., Montreal, Quebec, Canada. 4. E.C. Keystone, MD, The Rebecca MacDonald Centre for Arthritis, Mount Sinai Hospital; E. Rampakakis, PhD, JSS Medical Research Inc.; M. Movahedi, MD, PhD, Toronto General Hospital Research Institute, University Health Network; A. Cesta, MSc, Toronto General Hospital Research Institute, University Health Network; M. Stutz, MSc, JSS Medical Research Inc.; J.S. Sampalis, PhD, JSS Medical Research Inc.; F. Nantel, PhD, Janssen Inc.; K. Maslova, PhD, Janssen Inc.; C. Bombardier, MD, Toronto General Hospital Research Institute, University Health Network, and University of Toronto, DMO and IHPME, and Mount Sinai Hospital, Division of Rheumatology.
Abstract
OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS: Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.
OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS:Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.
Authors: Proton Rahman; Philip Baer; Ed Keystone; Denis Choquette; Carter Thorne; Boulos Haraoui; Andrew Chow; Rafat Faraawi; Wojciech Olszynski; John Kelsall; Emmanouil Rampakakis; Allen J Lehman; Francois Nantel Journal: BMC Rheumatol Date: 2020-09-19