Does the Type of Failure and the Choice of the Second Biologic Influence Response and Persistence on Medication in Rheumatoid Arthritis?

Background: The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily.
Methods: Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch.
Results: Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent.
Conclusion: Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic.
Competing Interests: L.B. has received sources of funding for research from Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, and Gilead; has a consulting agreement/is a member of the advisory board for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, and Teva; and received speaker honoraria agreements for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Fresenius Kabi, and Teva. M.M. has a faculty position (status) at the University of Toronto with no conflict of interest. G.R. is consultant to Corrona Research Foundation and CorEvitas, LLC. J.M.K. has no conflicts to report. The Corrona Research Foundation is a not-for profit 501(c)3 foundation. K.K. works at UMass Lowell and has a contract with Corrona Research Foundation. E.K. has received sources of funding for research from Amgen, Merck, and Pfizer; has a consulting agreement/is a member of an advisory board for AbbVie, Amgen, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc., Janssen Inc., Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, and Samsung Bioepsis; and received speaker honoraria agreements for Amgen, AbbVie, Celltrion, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sandoz, and Sanofi Genzyme.
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