Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis -The ANSWER cohort study-

Abstract

Background The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA). Methods This multi-center, retrospective study assessed 1,098 treatment courses of 661 patients with bDMARDs from 2009 to 2018 (females, 80.7%; baseline age, 71.7 years; disease duration 10.5 years; rheumatoid factor positivity 81.3%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.6; concomitant prednisolone dose 2.8 mg/day (45.6%) and methotrexate dose 4.4 mg/week (56.4%); and 60.2% patients were bio-naïve). Treatment courses included abatacept (ABT; n = 272), tocilizumab (TCZ; n = 234), etanercept (ETN; n = 184), golimumab (GLM; n = 159), infliximab (IFX; n = 101), adalimumab (ADA; n = 97), and certolizumab pegol (CZP; n = 51). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date and switched number of bDMARDs) by Cox proportional hazards modeling. Results A total of 51.2% of treatment courses were stopped, with 25.1% stopping due to lack of effectiveness, 11.8% due to toxic adverse events, 9.7% due to non-toxic reasons, and 4.6% due to remission. Drug retention rates for each discontinuation reason were as follows; lack of effectiveness [from 55.4% (ETN) to 81.6% (ABT); with significant differences between groups (Cox P<0.001)], toxic adverse events [from 79.3% (IFX) to 95.4% (ABT), Cox P = 0.043], and remission [from 94.2% (TCZ) to 100.0% (CZP), Cox P = 0.58]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 50.0% (ETN) to 78.1% (ABT) (Cox P<0.001). Conclusions ABT showed lowest discontinuation rate by 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 RA patients.

Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study

“…We recently reported drug retention rates among bDMARDs used in all age [16,17] as well as among the elderly population [18], factors associated with the achievement of bDMARDs-free remission [19], and the correlation of treatment response with family history of RA [20] from our cohort. Since then, we are continuously accumulating new data.…”

Better Retention of Abatacept Is Associated with High Rheumatoid Factor: A Five-Year Follow-Up Study of Patients with Rheumatoid Arthritis

“…2A). Ebina et al (2019) reported a three-year followup study with ABT showing that the lowest discontinuation rate out of seven bDMARDs in Japanese elderly patients with RA. Adjusted ABT retention rate at three years, excluding non-toxic reasons and remission, was 78.1%…”

“…Months Months (Ebina et al 2019). Kubo et al (2016) also documented the retention rate of ABT at week 52 was 73.7% in 194 patients with RA.…”

“…Previous studies have shown that ABT has a high retention rate of up to three years with tolerable adverse events (Ebina et al 2019). However, it remains unclear whether this is maintained in the longer term.…”

Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis -The ANSWER cohort study-

“…In this study, patients who were newly treated with at least 1 of 7 bDMARDs (ABT, ADA, CZP, ETN, GLM, IFX, and TCZ; including both intravenous and subcutaneous agents, but excluding bio-similar agents) or TOF from 2001 to 2019, with data on starting and discontinuation dates and reasons for discontinuation, were included. In addition, baseline demographic data such as age, sex, duration of disease, disease activity (Disease Activity Score in 28 joints using erythrocyte sedimentation rate [DAS28-ESR]), clinical disease activity index (CDAI), number of previously administered bDMARDs, concomitant doses and ratio of methotrexate (MTX) and prednisolone (PSL) (other glucocorticoids were calculated as equivalent dose to PSL; MTX or PSL dose was not considered when agents were not combined), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positivity, and Health Assessment Questionnaire [HAQ] disability index [DI] score were also collected [16][17][18].…”