Background:In clinical practice, when refractory rheumatoid arthritis (RA) is present, of which the definition implies previous use of at least two biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)), the next treatment choice often made is a bDMARD of another class (non-TNFis) [1]. However, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARDs treatment reduces their response [2]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. The choice of therapeutic agents for refractory RA is increasing, and its efficacy is expected. On the other hand, it is also true that some patients discontinued JAKis at a rate that cannot be overlooked because of insufficient efficacy. Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(3)Objectives:To evaluate real world efficacy of approved JAKis switching in patients with D2T RA who were unable to control their disease activity due to insufficient efficacy despite the sequential use of multiple bDMARDs and JAKis, focusing on the drug retention rate.Methods:In our hospital, RA was diagnosed according to the 1987 or 2010 classification criteria, and when two or more bDMARDs (including both TNFis and non-TNFis) were inadequately effective, it was defined as D2T RA. We retrospectively investigated patients who switched to JAKis for D2T RA. The drug retention rate was investigated by the Kaplan-Meier method, and the difference was tested by the Logrank test.Results:The 1-year retention rate of JAKis for D2T RA was 50.8% in TOF 38 cases [28 women, age average 70.2 years, disease duration average 12.4 years, past bDMARDs use average 3.5 drugs, MTX combination 9 cases, DAS28 ESR average 4.11] and 66.3% in BAR 35 cases [26 cases, 73.0 years old, 14.8 years, 4.17 agents, 9 cases, 3.68], and there was no significant difference (P = 0.30). Among them, there were 17 cases [11 cases, 70.6 years old, 13.5 years, 4.18 drugs, 2 cases, 3.65] of switching between JAKis, all of which were switching from TOF to BAR. The 1-year retention rate was 45.8% [reason for discontinuation: insufficient effect in 3 cases, adverse events in 6 cases], which was not significantly different but tended to be lower than 72.7% [reason for discontinuation: insufficient effect in 1 case, adverse event in 2 cases, patient’s convenience in 1 case] in 16 patients [13 cases, 76.3 years old, 17.1 years, 3.19 drugs, 7 cases, 3.69] who received BAR as the first JAKi for D2T RA patients (P = 0.089).Conclusion:Although the number of cases is small in the retrospective survey, it is suggested that the retention rate of BAR switched to D2T RA may be slightly lower in patients with a history of TOF discontinuation due to insufficient efficacy than in JAKi naive patients. It is expected that the number of new JAKi usage cases will increase in the future, and it is necessary to consider switching between other JAKis in addition to switching from BAR to TOF.References:[1]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[2]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[3]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared
Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rheumatoid arthritis with inadequate response to conventional disease-modifying antirheumatic drugs or tumour necrosis factor α inhibitors: systematic literature review and network meta-analyses