ANSWER Study: More Patients With RA Discontinue Adalimumab and Infliximab Due to Remission

A large study conducted to clarify the retention rates and reasons for discontinuation of biologics for rheumatoid arthritis (RA) confirmed earlier results that infliximab and adalimumab offer the best chance for remission.

The latest results came from the Kansai Consortium for Well-Being of Rheumatic Disease patients (ANSWER), an observational multicenter registry of patients with RA in Japan’s Kansai district. This study adds to what was known previously with a larger number of treatment courses and extends the results out to 36 months to see why patients stop treatment courses of biological disease-modifying antirheumatic drugs in real-world settings.

From 2009 to 2017, 4461 patients with RA were registered and 52,654 serial disease activities were available from the database.

The 7 biologics taken by these patients comprised 4 groups: anti—tumor necrosis factor (anti-TNF) monoclonal antibodies (infliximab, adalimumab, and golimumab), soluble TNF receptor or Fab fragments against TNF (etanercept and certolizumab pegol), the fusion protein CTLA4–Ig (abatacept), and an anti–interleukin-6 agent (tocilizumab).

Adalimumab and infliximab showed the highest discontinuation rate due to patient remission, followed by golimumab.

Tocilizumab showed the lowest discontinuation rate by lack of effectiveness, and abatacept showed the lowest discontinuation rate by toxic adverse events (AEs).

Also, abatacept showed the highest overall retention rates (excluding non-toxic reasons and remission) among the 7 biologics.

The study assessed 4466 treatment courses of 2494 patients. Patients had a mean age of 57.4 years and the majority were female with a mean disease duration of 8.5 years. Their rheumatoid factor positivity was 78.6% and the disease activity score in 28 joints using erythrocyte sedimentation rate was 4.3; concomitant medications were prednisolone at a dose of 2.7 mg/day (43.1%) and methotrexate at a dose 5 mg/week (61.8%); 63.6% patients were naïve to biologics.

Treatment courses included tocilizumab (n = 895), etanercept (n = 891), infliximab (n = 748), abatacept (n = 681), adalimumab (n = 558), golimumab (n = 464), and certolizumab pegol (n = 229).

A total of 56.9% of treatment courses were stopped:

• 25.8% stopped for lack of effectiveness
• 12.7% for non-toxic reasons
• 11.9% for toxic adverse events
• 6.4% for disease remission

By drug, retention rates for each discontinuation reason were:

• Lack of effectiveness (from 65.5% for infliximab to 81.7% for tocilizumab), with significant differences between groups (P <.001)
• Toxic adverse events (from 81.8% for infliximab to 94% for abatacept, P &thinsp;<.001)
• Remission (from 92.4% adalimumab and infliximab to 97.7% for etanercept, P &thinsp;<.001

Overall retention rates, excluding non-toxic reasons and remission for discontinuation, ranged from 53.4% for infliximab to 75.5% or abatacept (P <.001).

In terms of other possible confounders, the number of previously administered biologics, concomitant corticosteroids, male sex, and higher age at baseline exhibited negative effects on total drug retention rates.

Summing up what is known about this issue so far, the authors said that abatacept and certolizumab may exhibit lower toxic AEs compared with other agents. Infliximab, adalimumab, and golimumab may have some advantages in both achieving and maintaining biologic-free remission compared with other biologics.

Reference

Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis—the ANSWER cohort study [published online April 11, 2019]. Arthritis Res Ther. doi: 10.1186/s13075-019-1880-4.