Study Finds Higher Rates of Discontinuation Due to Remission Among Infliximab Users With RA

Randomized controlled trials of drugs that treat rheumatoid arthritis (RA) are sometimes limited to patients who differ from those treated in the real-world setting, which has led to observational studies of cohort-based registries being increasingly used to investigate the performance of biologic disease-modifying anti-rheumatic drugs (DMARDs) in treating RA. A multi-center retrospective study of Japanese patients, newly published in PLOS One, sought to describe treatment persistence and reasons for discontinuation among patients who were treating their RA with 1 of 7 biologic agents: adalimumab, etanercept, infliximab, golimumab, certolizumab pegol, tocilizumab, and abatacept.

The study investigated the Kansai Consortium for Well-Being of Rheumatic Disease Patients (ANSWER) cohort, which, from 2011 to 2016, identified 750 patients—who had 1037 treatment courses—who were being treated with 1 of the 7 agents of interest.

Reasons for treatment discontinuation of the 7 biologics were classified into 4 main categories: inefficacy, remission, toxic adverse events (AEs), and nontoxic reasons (such as patient preference or pregnancy).

Overall, 455 (43.9%) of all treatment courses were stopped by month 36:

• 217 (20.9%) were stopped due to inefficacy
• 113 (10.9%) were stopped for non-toxic reasons
• 86 (8.3%) were stopped due to toxic AEs
• 39 (3.8%) were stopped due to remission

Drug retention rates, using an adjusted Kaplan-Meier estimate, were as follows at month 36:

• Abatacept: 60.7%
• Adalimumab: 32.7%
• Certolizumab pegol: 43.3%
• Etanercept: 51.9%
• Golimumab: 45.4%,
• Infliximab: 31.1%
• Tocilizumab: 59.2%

Positive effects on treatment persistence were observed for concomitant methotrexate (hazard ratio [HR], 0.96; 95% CI, 0.94-0.98, P = .0002) or concomitant tacrolimus (HR, 0.63; 95% CI, 0.41-0.97, P = .036) treatment at baseline.

Negative effects on persistence were demonstrated with combined prednisolone treatment (HR, 1.02; 95% CI, 1.01-1.04, P = .0038), female sex (HR, 1.33; 95% CI, 1.06-1.69, P = .016), and number of previously administered biologics to treat RA (HR, 1.13; 95% CI, 1.04-1.22, P = .0031) at baseline.

At month 36, in adjusted models, drug retention rates due to inefficacy, toxic AEs, and remission, respectively, were as follows:

• Abatacept: 81.4%, 89.8%, 95.5%
• Adalimumab: 65.7%, 80.5%, 88.1%
• Certolizumab pegol: 60.7%, 83.9%, 91.1%
• Etanercept: 71.3%, 89.2%, 97.5%
• Golimumab: 68.5%, 85.5%, 94.7%
• Infliximab: 65.0%, 75.6%, 86.4%
• Tocilizumab 81.4%, 77.2%, 98.4%

Overall, say the authors, abatacept and tocilizumab showed higher retention rates, tocilizumab showed lower inefficacy rates, and abatacept showed lower rates of toxic events compared to infliximab, but infliximab showed higher discontinuation rates to remission than abatacept, etanercept, golimumab, and tocilizumab after adjusting for potential confounders.

Reference

Ebina K, Hashimoto M, Yamamoto W, et al. Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis—the ANSWER cohort study. PLOS One. 2018;13(3):e0194130. doi: 10.1371/journal.pone.0194130.