Background/Purpose:

Drug tolerability indicates both the patient’s and doctor’s satisfaction and useful summary measure of overall treatment effectiveness and toxicity. Although more than 5 years have passed since 7 biologics became available for patients with rheumatoid arthritis (RA) in our country, we still lack reliable evidence in directly compared drug tolerability and discontinuation reasons of 7 biologics in a real-world setting of RA.

Methods:

In this 7-center, retrospective study, 4466 biologics treatment courses from 2009 to 2017 (female 82.7%, baseline age 57.6y, Bio naïve 63.6%, disease duration 7.8y, rheumatoid factor positivity 76.3%, anti-cyclic citrullinated peptide antibody (ACPA) positivity 82.7%, disease activity score assessing 28 joints with CRP 3.9, modified Health Assessment Questionnaire 0.7, methotrexate 8.2 mg/week (limited to 16mg/week in our country), prednisolone 6.5 mg/day, number of each agent; tocilizumab (TCZ) 895, etanercept (ETN) 891, infliximab (IFX) 748, abatacept (ABT) 681, adalimumab (ADA) 558, golimumab (GLM) 464, and certolizumab pegol (CZP) 229) were included. Reasons for discontinuation of each biologic were analyzed and classified into 4 major categories: 1) inefficacy (both primary and secondary); 2) toxic adverse events (infection, skin or systemic reaction, hematologic, pulmonary, renal, cardiovascular complications and malignancies); 3) remission; and 4) nontoxic reasons (patient preference, change in hospital, desire for pregnancy, etc.). The judgment and reasons for discontinuation (only one reason were allowed to cite) depended on the decisions of each attending physician. Drug tolerability at 36 months were evaluate by Kaplan-Meier method for each discontinuation reasons, and adjusted by potent confounding factors (sex / age / ACPA positivity / switched biologics numbers) using a Cox proportional hazards model.

Results:

The causes of 7 biologics treatment discontinuation at 36 months were as follows. Drug inefficacy (45.4%), nontoxic reasons (22.4%), toxic adverse events (21.0%), and remission (11.2%). Adjusted cumulative incidence rates of each agent and discontinuous reason at 36 months were as follows. Drug inefficacy (TCZ 22.5%, ABT 26.1%, GLM 32.3%, CZP 33.5%, ETN 37.7%, ADA 38.6%, and IFX 38.7%; Cox P < 0.001), toxic adverse events (CZP 6.2%, ABT 7.4%, ETN 11.1%, TCZ 11.8%, ADA 14.9%, GLM 16.4%, and IFX 17.0%,; Cox P = 0.0049), and remission (ETN 3.1%, ABT 4.8%, CZP 5.3%, TCZ 5.8%, GLM 6.8%, ADA 10.2%, and IFX 10.7%; Cox P = 0.0018). Overall adjusted tolerability excluding nontoxic reasons and remission were ABT 68.5%, TCZ 68.3%, CZP 62.3%, GLM 56.5%, ETN 55.4%, ADA 52.2%, and IFX 50.9% (Cox P <0.001).

Conclusion:

TCZ and ABT showed lower inefficacy and higher overall retention, ABT and CZP showed lower toxic adverse events, and ADA and IFX showed higher bio-free induction due to remission compared to other biologics in background-adjusted models. These novel findings may contribute to adequate biologics selection in the clinical practice of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/drug-tolerability-and-discontinuation-reasons-of-7-biologics-in-4466-treatment-courses-of-rheumatoid-arthritis-the-answer-cohort-study/