Factors associated with the achievement of biological disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: the ANSWER cohort study

Motomu Hashimoto,Kosuke Ebina,Moritoshi Furu,Shuzo Yoshida,Koichi Akashi ,W Yamamoto ,Tôru Hirano ,Tomoyuki Fujii ,Akiko Ohnishi ,Taku Fujimura ,Koichiro Ohmura,Hiromu Ito,Yonsu Son,Ryuji Uozumi,Masaki Katayama,Koji Nagai,Ryota Hara,Masao Tanaka,Hideki Amuro,Tsuneyo Mimori

doi:10.1186/s13075-018-1673-1

Abstract

BackgroundClinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs (bDMARDs) in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR)). It is unknown which bDMARD is advantageous for achieving BFR or under which conditions BFR can be considered. This study aimed to determine the factors associated with BFR achievement in clinical practice.MethodsPatients with RA were enrolled from a Japanese multicenter observational registry. Patients with RA who achieved clinical remission (Disease Activity Score 28—C-reactive protein < 2.3) at the time of bDMARD discontinuation were included. Serial disease activities and treatment changes were followed up. BFR was considered to have failed if the disease activity exceeded the remission cutoff value or if bDMARDs were restarted.ResultsOverall, 181 RA patients were included. BFR was maintained in 21.5% of patients at 1 year after bDMARD discontinuation. BFR was more successfully achieved after discontinuation of anti-tumor necrosis factor (TNF) monoclonal antibodies (TNFi(mAb)) (infliximab, adalimumab, and golimumab), followed by CTLA4-Ig (abatacept), soluble TNF receptor or Fab fragments against TNF fused with polyethylene glycol (etanercept and certolizumab), and anti-interleukin-6 receptor Ab (tocilizumab). After multivariate analysis, sustained remission (> 6 months), Boolean remission, no glucocorticoid use at the time of bDMARD discontinuation, and use of TNFi(mAb) or CTLA4-Ig remained as independent factors associated with BFR.ConclusionsBFR can be achieved in some patients with RA after bDMARD discontinuation in clinical practice. Use of TNFi(mAb) or CTLA4-Ig, sustained remission, Boolean remission, and no glucocorticoid use at the time of bDMARD discontinuation are advantageous for achieving BFR.

Highlights

Clinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR))
Analysis of variance and the chi-squared test were used to compare the clinical characteristics among different groups for continuous variables and categorical variables, respectively bDMARD biological disease-modifying antirheumatic drug, TNF inhibitor (TNFi)(mAb) monoclonal antibodies against TNF, TNFi(R/P) soluble TNF receptor or Fab fragments against TNF fused with polyethylene glycol, CTLA4-Ig abatacept, IL-6Ri interleukin-6 receptor inhibitor, DAS28-CRP Disease Activity Score 28—C-reactive protein, MTX methotrexate, ACPA anti-citrullinated protein antibodies, RF rheumatoid factor, TNF tumor necrosis factor bDMARDs
Hazard ratio (HR) with 95% Confidence interval (CI) obtained using Cox’s proportional hazard model bDMARD biological disease-modifying antirheumatic drug, HR hazard ratio, CI confidence interval, TNFi(mAb) monoclonal antibodies against TNF, TNFi(R/P) soluble TNF receptor or Fab fragments against TNF fused with polyethylene glycol, CTLA4Ig abatacept, IL-6Ri interleukin-6 receptor inhibitor, DAS28-CRP Disease Activity Score 28—C-reactive protein, CCP cyclic citrullinated peptide, TNF tumor necrosis factor, RF rheumatoid factor, MTX methotrexate

Summary

Introduction

Clinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs (bDMARDs) in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR)). It is unknown which bDMARD is advantageous for achieving BFR or under which conditions BFR can be considered. Remission or low disease activity is a realistic goal for most patients After achieving remission, it would be advantageous if remission could be maintained without using bDMARDs (bDMARDs-free remission (BFR)) because of the associated cost-effectiveness and prevention of adverse events. Discontinuation of infliximab (IFX) was attempted in patients with established RA, and low disease activity was maintained in 43% of patients at 1 year after discontinuation in the RRR study [5]. “Drug-free remission” was maintained after discontinuation of the anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) in 9% of patients in the DREAM study [16] and 14% of patients in the ACT-RAY study [17], respectively, after 1 year

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