Response to Biologic Disease-Modifying Anti-Rheumatic Drugs after Discontinuation of Anti-Tumor Necrosis Factor Alpha Agents for Rheumatoid Arthritis

Abstract

IntroductionThe aim of this study was to compare the response between subsequent use of anti-tumor necrosis factor α (anti-TNF) agents and biologic disease-modifying anti-rheumatic drugs (bDMARD) with other mechanism of action (MOA) in rheumatoid arthritis (RA) patients with history of anti-TNF treatment as their first bDMARD.MethodsA retrospective chart review was conducted at eight community-based rheumatology practices in the United States in 2012. Routine Assessment of Patient Index Data 3 (RAPID3) response was measured by comparing baseline and 6-month scores. Poor response was defined as decrease <1.8 points, follow-up score >12, or treatment discontinuation before 6 months. Percentages of patients with good and good or moderate RAPID3 response were compared for second and third biologics. Multivariate models controlled for potential confounders.ResultsOf 176 patients whose charts were abstracted, 122 (69.3%) received another anti-TNF agent after they discontinued their first anti-TNF. RAPID3 scores were available for 160 patients. A patient receiving a second bDMARD with another MOA had a higher good or moderate response than a patient receiving anti-TNF (53.5 vs. 30.7%, p = 0.01). In the multivariate models, treatment with another MOA was more likely to produce a good RAPID3 response [odds ratio (OR), 2.42; 95% confidence interval (CI), 1.05–5.58] or a good or moderate response (OR, 2.21; 95% CI, 1.23–3.97) than treatment with an anti-TNF.ConclusionIn patients who have discontinued anti-TNF agents as their first bDMARD, RAPID3 response rates are better for those receiving agents with a different MOA rather than another anti-TNF. Physicians should consider using a bDMARD with a different MOA as the next bDMARD for RA patients whose anti-TNF agent has failed.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-014-0002-7) contains supplementary material, which is available to authorized users.

Effectiveness of golimumab in rheumatoid arthritis patients with inadequate response to first-line biologic therapy: Results from a Japanese post-marketing surveillance study

“…Recently, switching to alternative bDMARDs that have distinct mechanisms of action has been advocated as a therapeutic option. Several lines of evidence from an RCT [22], retrospective cohort studies [19][20][21]23] and a systemic review [18] have suggested that swapping to non-TNF inhibitors may be more effective than cycling TNF inhibitors in RA patients who have shown an inadequate response to TNF inhibitors. Nevertheless, it remains elusive whether the reverse is also true.…”

“…Despite these interesting findings, limited information has hitherto been available from the real-world clinical setting with regard to the benefits of switching to GLM in heterogeneous patient populations. The findings of recent studies [18][19][20][21][22][23], but not all [24,25], have supported the notion that switching to another bDMARD with a different mode of action (swapping strategy) is superior to the cycling strategy [26]. In this context, several RCTs have examined the efficacy of second-line non-TNF inhibitor therapy using agents such as tocilizumab, abatacept, and sarilumab in patients who failed to respond to first-line TNF inhibitor therapy [27][28][29][30][31].…”

Cost-Effectiveness of Sarilumab Added to Methotrexate in the Treatment of Adult Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors

“…37 This conservative assumption ascribed to the model addressed the limited evidence on efficacy per line of treatment, despite other contrasting evidence suggesting that efficacy of TNFis is reduced with each subsequent TNFi. 6,7,22 Finally, the additional strengths of the current cost-effectiveness analysis include its conduct according to best practice guidelines. 60 Furthermore, the results remained robust in various sensitivity analyses.…”

“…This strategy is supported by a significant body of evidence from claims analyses indicating beneficial outcomes associated with MOA switching, [5][6][7][8][9][10][11][12][13] while other evidence from a randomized control trial (RCT) and other claims analyses point to conflicting evidence of enhanced outcomes associated with TNFi cycling. [14][15][16] Nonetheless, cycling between TNFi treatments after failure with a previous TNFi remains commonplace, 5,15,[17][18][19][20][21][22][23] with a number of factors likely influencing clinical practice, including compliance with the health insurance mandate (e.g., step-edit requirement) and rheumatologist or patient preferences. 24,25 While rheumatologists have a substantial number of therapeutic options currently available for patients with RA, there is a lack of clarity on the optimal approach for patients who have inadequate response or intolerance to TNFi (TNF-IR).…”