Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy

Abstract

Introduction: To examine treatment persistence and clinical outcomes associated with switching from a tumor necrosis factor inhibitor (TNFi) to a medication with a new mechanism of action (MOA) (abatacept, anakinra, rituximab, tocilizumab, or tofacitinib) versus cycling to another TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) among patients with rheumatoid arthritis.

Methods: This retrospective, longitudinal study included patients with rheumatoid arthritis in the JointMan^® US clinical database who received a TNFi in April 2010 or later and either cycled to a TNFi or switched to a new MOA therapy by March 2015. Cox proportional hazards models were used for time to non-persistence (switching or discontinuing). An ordinary least squares regression model compared 1-year reduction from baseline for the Clinical Disease Activity Index (CDAI).

Results: There were 332 (54.2%) TNFi cyclers and 281 (45.8%) new MOA switchers. During a median follow-up of 29.9 months, treatment persistence was 36.7% overall. Compared with new MOA switchers, TNFi cyclers were 51% more likely to be non-persistent (adjusted hazard ratio, 1.511; 95% CI 1.196, 1.908), driven by a higher likelihood of switching again (adjusted hazard ratio, 2.016; 95% CI 1.428, 2.847). Clinical outcomes were evaluable for 239 (53.3%) TNFi cyclers and 209 (46.7%) new MOA switchers. One-year mean reduction in CDAI from baseline to end of follow-up was significantly higher for new MOA switchers than TNFi cyclers (-7.54 vs. -4.81; P = 0.037), but the difference was not statistically significant after adjustment for baseline CDAI (-6.39 vs. -5.83; P = 0.607).

Conclusion: In this study, TNFi cycling was common in clinical practice, but switching to a new MOA DMARD was associated with significantly better treatment persistence and a trend toward greater CDAI reduction that was not significant after adjustment for baseline disease activity.

Funding: Sanofi and Regeneron Pharmaceuticals.

Keywords: Biologic disease-modifying anti-rheumatic drugs; Persistence; Rheumatoid arthritis; Rheumatology; TNFi; Treatment outcome; Treatment selection; Tumor necrosis factor inhibitor; bDMARDs.

Fig. 1

The JointMan^® color-coded anatomical (homunculus) diagram, tied to calculated algorithms and validated tests. Source: Ref. [43]. (Reproduced with permission from Discus Analytics LLC)

Fig. 2

Study population flow chart. CDAI Clinical Disease Activity Index, MOA mechanism of action, TNFi tumor necrosis factor inhibitor

Fig. 3

Kaplan-Meier analysis of treatment patterns for the index drug. a Time to non-persistence. b Time to switching again. c Time to discontinuation. DMARD disease-modifying antirheumatic drug, MOA mechanism of action, TNFi tumor necrosis factor inhibitor

Fig. 4

Cox models: hazard ratios for time to non-persistence, time to switching again, and time to discontinuation. CDAI Clinical Disease Activity Index, CI confidence interval, HR hazard ratio, MOA mechanism of action, MTX methotrexate, TNFi tumor necrosis factor inhibitor

Fig. 4

Cox models: hazard ratios for time to non-persistence, time to switching again, and time to discontinuation. CDAI Clinical Disease Activity Index, CI confidence interval, HR hazard ratio, MOA mechanism of action, MTX methotrexate, TNFi tumor necrosis factor inhibitor

Fig. 5

One-year persistence, switching, and discontinuation rates among patients with ≥1 year of follow-up. *P < 0.05 for new mechanism of action (MOA) switchers vs. tumor necrosis factor inhibitor (TNFi) cyclers

Fig. 6

Achievement of a minimally clinically important difference in CDAI score from baseline to end of follow-up. Baseline was the score closest to the study index date between 6 months pre-index and 1 month post-index; end of follow-up was the visit closest to (but not greater than) 12 months post-index. CDAI Clinical Disease Activity Index, MOA mechanism of action, TNFi tumor necrosis factor inhibitor