Prior Biologics Exposure May Affect Drug Retention in Patients with Rheumatoid Arthritis

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Among patients with rheumatoid arthritis who were bDMARD-naïve, the highest overall retention rate was observed with abatacept.

A study published in Arthritis Research & Therapy outlined the drug retention profiles of patients with and without prior exposure to biological disease-modifying anti-rheumatic drugs (bDMARDs). Among patients who were bDMARD-naïve, the highest overall retention rate was observed with abatacept. Among patients who were bDMARD-switched, tocilizumab had the highest retention.

Investigators extracted data from a multicenter registry of patients with rheumatoid arthritis (RA) residing in Japan. The study assessed patients who had received treatment with bDMARDs and/or tofacitinib between 2001 and 2019. Patients were categorized as bDMARD-naïve or bDMARD-switched based on prior treatment exposure. Demographic and clinical factors were captured at baseline, including age, sex, disease duration, rheumatoid factor positivity, Disease Activity Score in 28 joints (DAS28), and concomitant prednisolone or methotrexate use. Treatment courses of interest were tofacitinib and bDMARDs. The primary outcome was drug discontinuation at 36 months. Reasons for discontinuation were captured by physician report. Gray’s test was used to assess differences in discontinuation rates between patient groups.

The study cohort comprised 3897 patients (82.3%, female). Baseline age was 57.4 years; mean disease duration was 8.5 years; and 78.4% were rheumatoid factor positive. A total of 4115 treatment courses were observed: 2737 bDMARD-naïve courses and 1678 bDMARD-switched courses. The majority (59.5%) of bDMARD-switched courses were the patients’ second agent. Treatment courses included tofacitinib (n=101) and the following bDMARDs: abatacept (n=663), adalimumab (n=536), certolizumab pegol (n=226), etanercept (n=856), golimumab (n=458), infliximab (n=724), and tocilizumab (n=851). Tofacitinib was only administered to bDMARD-switched cases. In the bDMARD-naïve group, rates of drug discontinuation due to lack of effectiveness ranged from 13.7% (abatacept) to 26.9% (certolizumab pegol) (P <.001 between agents). In the bDMARD-switched group, rates ranged from 18.9% (tocilizumab) to 46.1% (certolizumab pegol) (P <.001).

Drug discontinuation rates due to toxic adverse events ranged from 4.6% (abatacept) to 11.2% (etanercept) in the bDMARD-naïve group (P <.001) and 5.0% (etanercept) to 15.7% (tofacitinib) in the bDMARD-switched group (P =.004). In the bDMARD-naïve group, discontinuation due to remission was highest in patients taking infliximab (10.0%) and lowest in patients taking etanercept (2.9%) (P <.001). Among bDMARD-switched cases, discontinuation due to remission ranged from 1.1% with certolizumab pegol to 3.3% with golimumab (P <.001). Excluding discontinuation due to non-toxic adverse events, retention rates were highest with abatacept in bDMARDs-naïve patients. Among bDMARDs-switched cases, tocilizumab had the greatest overall retention.

Study limitations include the lack of information on drug administration; intravenous and subcutaneous bDMARDs could not be directly compared. Additionally, data on dose changes were not available.

The investigators conclude that their findings support the importance of precision medicine: appropriate use of bDMARDs and tofacitinib may depend on prior medication history.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ebina K, Hirano T, Maeda Y, et al. Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study [published online June 15, 2020]. Arthritis Res Ther. doi: 10.1186/s13075-020-02232-w