In a study of 7 biological disease-modifying antirheumatic drugs (bDMARDs) in an elderly population with rheumatoid arthritis, abatacept had the lowest rate of discontinuation because of ineffectiveness or toxic adverse events, according to study results published in PLoS One.
This retrospective, multicenter study included 661 individuals undergoing 1098 bDMARD treatment courses between 2009 and 2018, 80.7% of whom were women and whose age at baseline was 71.7 years. Mean disease duration was 10.5 years; mean Disease Activity Score in 28 joints was 4.6 and mean rheumatoid factor positivity was 81.3%. Although 60.2% of the group was biologic-naive, 45.6% received prednisolone 2.8 mg/d, and 56.4% received methotrexate 4.4 mg/wk. Abatacept was administered to 272 individuals, tocilizumab to 234, etanercept to 184, golimumab to 159, infliximab to 101, adalimumab to 97, and certolizumab pegol to 51. The Kaplan-Meier method was used to estimate drug retention and reasons for discontinuation at 3 years, with adjustments made for sex, age, disease duration, starting date, switched number of bDMARDs, and concomitant methotrexate and prednisolone using Cox proportional hazards. Reasons for discontinuation were stratified into lack of effectiveness, remission of disease, toxic adverse events, and nontoxic reasons such as change in hospital or desire for pregnancy.
Treatment courses were discontinued in 51.2% of cases, among which 25.1% were discontinued for lack of effectiveness, 11.8% for toxic adverse events, 9.7% for nontoxic reasons, and 4.6% for remission of disease. Drug retention rates ranged from 55.4% (etanercept) to 81.6% (abatacept) for lack of effectiveness (Cox P <.001); from 79.3% (infliximab) to 95.4% (abatacept) for toxic adverse events (Cox P =.043); and from 94.2% (tocilizumab) to 100% (certolizumab pegol) for remission (Cox P =.58). The 3-year drug retention rates were 78.1% (abatacept), 66.8% (tocilizumab), 64.8% (golimumab), 57.6% (adalimumab), 55.6% (certolizumab pegol ), 52.5% (infliximab), and 50% (etanercept); Cox P <.001.
Limitations to this study include a lack of recorded criteria for discontinuation, a variety of patient backgrounds that may have confounded results, a lack of monitoring of minor dose changes, a lack of differentiation between intravenous and subcutaneous bDMARDS, and a potentially small rate of prescription of certolizumab pegol.
The researchers concluded that “[abatacept] showed lowest discontinuation rate [due to] lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly [rheumatoid arthritis] patients.”
This study received funding from UCB Japan. The study authors also reported financial relationships with pharmaceutical companies. For a full list of author disclosures, please refer to the original study.
Ebina K, Hashimoto M, Yamamoto W, et al. Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis – the ANSWER cohort study [published online May 8, 2019]. PLoS One. doi:10.1371/journal.pone.0216624