CP-200 Drug continuation rate of ABATACEPT in patients with rheumatoid arthritis

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

Download Full-text

AB0345 EFFICACY OF JAK INHIBITORS IN REFRACTORY RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1712 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1472.1-1472

Author(s):

M. Kamiya

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Duration ◽

Inhibitor Therapy ◽

Cumulative Number ◽

Jak Inhibitor ◽

Continuation Rate ◽

Jak Inhibitors ◽

Refractory Rheumatoid Arthritis ◽

Continuation Rates

Background:Disease-modifying antirheumatic drugs (DMARDs) have been the main agents for treating rheumatoid arthritis (RA) unless there are serious clinical restrictions or contraindications such as comorbidities. With inefficacy of conventional synthetic DMARDs (e.g., methotrexate), biological DMARDs (bDMARDs) are now available to suppress progression of joint destruction. However, bDMARDs cannot control disease activity in some patients, so JAK inhibitors targeting different cytokines are expected to be beneficial.Objectives:This study investigated factors associated with the efficacy and continuation of JAK inhibitor therapy in patients with refractory RA for whom disease activity was not adequately controlled even with multiple sequentially administered bDMARDs with different targets.Methods:We obtained the number of bDMARDs used and the various reasons for discontinuing therapy in our hospital from January 2005 to December 2019. Kaplan–Meier analysis was used to obtain the therapy continuation rate, and the log-rank test was used to examine the difference in therapy continuation rate. Refractory RA was defined as RA with inefficacy with 3 or more bDMARDs with different targets (1 or more tumor necrosis factor inhibitor, a selective costimulation modulator abatacept, and an interleukin 6 receptor inhibitor tocilizumab). We then examined patients with refractory RA who had received tofacitinib (TOF) or baricitinib (BAR) therapy after discontinuation of a series of bDMARDs due to unsatisfactory response. Various statistical tests were performed to identify predictors of ≥ 6-month continuation of JAK inhibitor therapy that achieves low disease activity without increases in prednisolone (PSL) use. Explanatory variables included characteristics of patients at initiation of TOF or BAR therapy: age, sex, disease duration, number of bDMARDs previously used, concomitant methotrexate dose, concomitant PSL dose, DAS28-ESR value, presence of rheumatoid factor or anti-CCP antibodies, and MMP-3 level.Results:A cumulative number of 782 bDMARDs were administered to 362 RA patients by December 2019. The most common reason for discontinuation was inefficacy (51.8%), followed by adverse events including deaths (30.1%), patients’ circumstances such as hospital transfer (9.2%), switch to biosimilars (5.2%), and remission (3.7%). The bDMARDs continuation rate and the number of bDMARDs used were 69.6% and 2.17 for 5 years and 53% and 2.83 for 10 years, respectively, if the switch was considered to be continuous due to insufficient effect. The 6-month continuation rates were not significantly different between TOF and BAR (60 patients [62.3%] vs. 39 patients [81.3%], respectively; P = 0.147). In patients with refractory RA, continuation rates were not significantly different between TOF and BAR (19 patients [42.1%] vs. 11 patients [54.5%], respectively; P = 0.86). Only TOF-treated patients, not BAR-treated patients, showed significant differences in disease duration (226.1 months in the continued group vs. 111.8 months in the discontinued group; P = 0.035) and concomitant PSL dose (0.71 mg vs. 4.0 mg, respectively, P = 0.045).Conclusion:There are not a few patients with refractory rheumatoid arthritis. These findings, albeit retrospective, suggest that low concomitant PSL dose and long disease duration at the time of TOF therapy initiation were factors for TOF continuation. Therapy continuation rate was decreased in patients with refractory RA, and further study on switching therapy between different JAK inhibitors is anticipated.References:[1]Souto A, Maneiro JR & Gomez-Reino JJ. Rate of diccontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care database. Rheumatology (Oxford), 55, 523-534, 2016Disclosure of Interests:None declared

Download Full-text