Background: Patients with RA frequently struggle with intolerance of MTX and adherence to MTX remains highly variable. Guidelines conditionally recommend the tapering of MTX before tapering biologic (b)DMARDs, but acknowledge there is an absence of direct evidence. Prior reviews on this topic have focused on tapering of MTX from combination treatment with TNF-inhibitors(i) only ¹ . There have been no updated reviews addressing MTX tapering from other targeted therapies such as IL6-i or JAK-i, nor has there been a systematic review addressing this question.

Objectives: To determine the feasibility of tapering MTX to targeted therapy (bDMARDs or JAKi) alone in patients whose RA is controlled (LDA or remission).

Methods: A systematic literature search combing MeSH terms and keywords was conducted in Medline, Embase and Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Non-English and animal studies were excluded. Meta-analyses were conducted using random effects models. Forest and funnel plots were created and heterogeneity was calculated.

Results: Our search identified 5762 citations. After removal of duplicates and screening title/abstract using the COVIDENCE platform, 504 full-text articles were reviewed. Of the 10 articles meeting our inclusion criteria of tapering MTX to monotherapy with a targeted therapy, 3 studies tapered to etanercept, 3 to tocilizumab, 1 to tofacitinib, 1 to certolizumab pegol, 1 to adalimumab and 1 to abatacept monotherapy. Nine studies were RCTs and one was a long-term extension study (LTE) ( Table 1 ). Disease duration was longer in 7 studies (6-11 years) and early in 3 studies (1-9 months). The MTX tapering strategy was gradual in 2 and rapid in 8 studies. Follow-up ranged from 3 -18 months in RCTs, and up to 3 years in the LTE. Studies reporting outcomes up to 1 year after tapering had remission rates ranging 48-76%, but this dropped to 40% in one study reporting 18- month remission outcomes. Our meta-analysis conducted in 2000 RA participants from 10 studies showed that patients who tapered MTX to targeted therapy alone could maintain remission with an overall pooled OR of 0.81 (0.68, 0.97) ( Figure 1 ). There was no heterogeneity among the studies in this group (I ² =0.0%, p=0.788). Our funnel plot indicated high precision and potentially less publication bias. No significant difference in remission outcomes between early RA [OR 0.63 (0.33, 1.18)] and established RA [OR 0.84 (0.69, 1.03)] was observed.

Conclusion: Patients with controlled RA have a high probability of maintaining disease control after tapering their MTX to targeted therapy alone, up to 18 months. This review may inform patients with controlled disease on any of a range of targeted therapies and MTX, but who are struggling with MTX-related adverse effects and wish to taper it. Longer follow-up studies with attention to radiographic, functional and patient reported outcomes are needed. The possibility of disease worsening must be discussed with the patient in advance with careful follow-up and prompt re-treatment of disease worsening.

REFERENCES:

[1]Subesinghe S, Scott IC. Expert Rev Clin Pharmacol 2015;8:751-60.

Disclosure of Interests: Charis Meng: None declared, Diviya Rajesh: None declared, Deanna Jannat-Khah Shareholder of: AstraZeneca, Cytodyn, Walgreens, Omar Bruce: None declared, Bridget Jivanelli: None declared, Vivian Bykerk Consultant of: Amgen, Bristol Myers Squibb, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, UCB., Grant/research support from: NIH (NIAID/NIAMS) grant 1UH2AR067691-01 GRANT11652401 and The Cedar Hill Foundation; institution received grants from Bristol Myers Squibb and Amgen;