Background/Purpose: RA patients who fail to achieve treatment targets with conventional synthetic DMARDs (csDMARDs) can be treated with biologics. Randomized controlled trials (RCTs) have shown IL-6 receptor inhibitors (IL-6i) to be superior to TNF-α inhibitors (TNFi; adalimumab) as monotherapy in biologic-naïve patients with high disease activity. There is limited research comparing the effectiveness of TNFi vs IL-6i as monotherapy or in combination with csDMARDs in biologic-experienced RA patients with moderate/high disease activity. This real-world retrospective study based on CorEvitas’ RA registry aimed to address the gap.

Methods: Adult RA patients who initiated a TNFi or IL-6i during or after January 2010 were included if they had: a history of 1 or 2 biologic/targeted synthetic DMARDs (b/tsDMARDs) prior to initiation, moderate/high disease activity at initiation, and a follow-up visit at 6 (± 3) months after initiation. Cohorts included TNFi and IL-6i initiators, both with subgroups initiating as mono- or combination (with MTX) therapy. Mixed effects regression models with random intercept for patients were used to evaluate the impact of therapy class on the following outcomes: disease burden (HAQ-DI, pain visual analog scale [VAS, 0-100], patient global assessment, and fatigue [1-item VAS, 0-100]), non‑inflammatory pain (NIP; NIP1: tender joint count [TJC, 28] – swollen joint count [SJC, 28] ≥7; NIP2: SJC [28]/TJC [28] < 0.5), and clinical disease activity index (CDAI). Unadjusted and covariate-adjusted effects (β, 95% confidence interval [CI] for linear regressions and odds ratio [OR, 95% CI] for logistic regressions) were reported.

Results: Patients initiating IL-6i (n=286) vs TNFi monotherapy (n=737; Figure 1) were older (60.0 vs 55.4 years; P< 0.001), had longer history of RA (12.2 vs 10.0 years; P=0.001), higher CDAI at baseline (26.9 vs 24.9; P=0.02), and were more likely to initiate as 3rd line therapy (57.0% vs 30.9%; P< 0.001). IL-6i (n=401) vs TNFi (n=1315) combination therapy initiators had higher CDAI at baseline (26.7 vs 24.8; P=0.007) and were more likely to initiate as 3rd line therapy (56.4% vs 28.7%; P< 0.001; Table 1). There were no statistically significant differences in outcomes between IL-6i and TNFi initiators (as mono- or combination therapy). One-third of IL-6i and TNFi mono- (adjusted OR [aOR]: 0.99 [0.59, 1.67]) and combination therapy initiators (aOR: 0.96 [0.66, 1.38]) achieved low disease activity (Table 2).

Conclusion: In this real-world analysis, no significant differences were noted in the outcomes for IL-6i vs TNFi initiators (as mono- or combination therapy). Compared with prior RCTs, patients in this study were biologic‑experienced, had lower disease activity, and were unblinded to treatment, which could have contributed to a reduced difference in effectiveness between these treatments. In addition, selection of therapy in this real-world study may be influenced by factors that cannot be measured or controlled.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-effectiveness-of-tnf-inhibitor-vs-il-6-receptor-inhibitor-as-monotherapy-or-combination-therapy-with-methotrexate-in-patients-with-rheumatoid-arthritis-analysis-from-corevitas-ra/