Objectives There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of ‘usual’ (5 mg every 4 weeks) versus ‘fast’ (5 mg every 2 weeks) escalation of oral MTX.
Methods This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.
Results 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.
Conclusion A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.
Trial registration number CTRI/2018/12/016549
- disease activity
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
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SJ and VD are joint first authors.
Handling editor Josef S Smolen
Contributors VDhi, SiJ, SN and AA designed the study. SiJ, VDhi, AA, RG, SN, SM, SKS, AS and SaJ were involved in collecting patients’ data and executing the study. BL, AK, SM and VDha performed the laboratory procedures and interpreted them. VDhi and SiJ performed the statistical analyses. VDhi and SiJ drafted the manuscript; AA and RG gave critical inputs. All authors approved the final submitted version of the manuscript.
Funding A Departmental grant (Department of Internal Medicine, Postgraduate Institute of Medical Education and Research) and grants from the Indian Rheumatology Association and Physician Research Foundation (Association of Physicians of India) were used to fund the laboratory assays used in the study.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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