Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

Abstract

ObjectivesThis multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in a real-world cohort of patients with rheumatoid arthritis.MethodsThe study included 6666 treatment courses (bDMARD-naïve or JAKi-naïve cases, 55.4%; tumour necrosis factor inhibitors (TNFi) = 3577; anti-interleukin-6 receptor antibodies (aIL-6R) = 1497; cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) = 1139; JAKi=453 cases). The reasons for discontinuation were divided into four categories (ineffectiveness, toxic adverse events, non-toxic reasons and remission); multivariate Cox proportional hazards modelling by potential confounders was used to analyse the HRs of treatment discontinuation.ResultsTNFi (HR=1.93, 95% CI: 1.69 to 2.19), CTLA4-Ig (HR=1.42, 95% CI: 1.20 to 1.67) and JAKi (HR=1.29, 95% CI: 1.03 to 1.63) showed a higher discontinuation rate due to ineffectiveness than aIL-6R. TNFi (HR=1.28, 95% CI: 1.05 to 1.56) and aIL-6R (HR=1.27, 95% CI: 1.03 to 1.57) showed a higher discontinuation rate due to toxic adverse events than CTLA4-Ig. Concomitant use of oral glucocorticoids (GCs) at baseline was associated with higher discontinuation rate due to ineffectiveness in TNFi (HR=1.24, 95% CI: 1.09 to 1.41), as well as toxic adverse events in JAKi (HR=2.30, 95% CI: 1.23 to 4.28) and TNFi (HR=1.29, 95%CI: 1.07 to 1.55).ConclusionsTNFi (HR=1.52, 95% CI: 1.37 to 1.68) and CTLA4-Ig (HR=1.14, 95% CI: 1.00 to 1.30) showed a higher overall drug discontinuation rate, excluding non-toxicity and remission, than aIL-6R.

The impact of glucocorticoid use on the outcomes of rheumatoid arthritis in a multicenter ultrasound cohort study

“…On the contrary, a multicenter retrospective study on b/tsDMARDs revealed that the concomitant use of oral glucocorticoids at baseline was associated with the discontinuation of b/tsDMARDs due to their ineffectiveness, 24 with which our results are consistent.…”

“…Examination sites included bilateral wrist and first to fifth metacarpophalangeal and proximal interphalangeal joints every 3 months after the introduction of b/tsDMARDs. Systematic multiplanar grayscale (GS) and power Doppler (PD) joint examinations were performed using a multifrequency linear transducer (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) and one of the following scanners: Toshiba AplioXG, Aplio300 or Aplioi800, GE Logic series 7 or 8 or HITACHI HI VISION Avius, and Noblus or HI VISION Preirus. All scanners were the latest machines available at the time of the study with joint mode.…”

Impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab in axial spondyloarthritis (axSpA): data from the French multicentre retrospective FORSYA study

“…While investigating the predisposing factors of a retention rate, the ranking order of DMARD administration is consistently retained in multivariate analysis as statistically significant 13 14 17 with a better drug retention rate when the drug was initiated as the first or second biologic line therapy.…”

“…This is why, in RWD studies, the percentage of patients still on treatment over time, known as the drug retention rate, has been proposed as a surrogate measure of drug efficiency. [11][12][13] Studies conducted by pharmaceutical companies after drug approval are referred to as postmarketing surveillance studies. 13 These studies are often based on RWD and are typically conducted shortly after the drug becomes available in a specific country (launch time), particularly when mandated by health authorities.…”

“…[11][12][13] Studies conducted by pharmaceutical companies after drug approval are referred to as postmarketing surveillance studies. 13 These studies are often based on RWD and are typically conducted shortly after the drug becomes available in a specific country (launch time), particularly when mandated by health authorities. Previous RWD on the use of secukinumab in axSpA in France revealed that it was primarily prescribed as a thirdline or even later biologic therapy, likely due to patients who had not responded to multiple antitumour necrosis factor (TNF) therapy seeking a new treatment option.…”