Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial

Abstract

ObjectivesThere 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.MethodsThis 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.Results178 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.ConclusionA 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 numberCTRI/2018/12/016549

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

“…Another Indian investigator-blinded trial (high RoB) compared two different MTX dosage escalation strategies in MTX-naïve patients—starting with 15 mg once weekly, MTX was either increased by 5 mg every 2 weeks or by 5 mg every 4 weeks. No efficacy differences in EULAR good response rates were observed at week 16 (22.5% vs 28.1%; p=0.39; for every 2 weeks and every 4 weeks MTX escalation, respectively) 12…”

A chinese medicine formula (kunbixiao granule) for female rheumatoid arthritis: Study protocol for a double-blind, randomized, placebo-controlled trial

“…The DAS28-CRP is widely used as an indicator of RA disease activity and response to treatment, and clinical trials have used DAS28 to assess treatment effect ( Gardiner et al, 2005 ; Jain et al, 2021 ; Zhang et al, 2022 ). A change of ≥1.2 score is considered clinically significant difference ( Van Gestel et al, 1998 ).…”

Methotrexate treatment strategies for rheumatoid arthritis: a scoping review on doses and administration routes

“…Most studies were conducted in Europe ( n = 5, 41.7%), followed by Asia ( n = 4, 33.3%) and America ( n = 3, 25.0%). The included studies were undertaken in a single centre (including hospitals or clinics), while 4 trials were multicenter studies [ 31 , 34 – 36 ]. Included studies were grouped into two broad categories that represent (i) the different starting dosages and the plan for dose escalation ( n = 9) [ 28 , 29 , 33 – 41 ] and (ii) the routes of administration for MTX ( n = 3) [ 30 – 32 , 34 ].…”

“…The included trials recruited patients with a broad range of time from RA diagnosis (from 2.1 to 14.4 years), with a mean of 5.8 (± 4.8) years. Only two studies [ 28 , 36 ] reported data on body mass index, with a mean of 24.2 (± 0.9) kg/m 2 . The mean Disease Activity Score for 28 joints (DAS28) score was reported by three trials [ 36 , 38 , 39 ] with scores ranging from 4.5 to 5.4 (mean 5.2 [± 0.4]), while only one study [ 40 ] provided data on the basal ACR functional class with a mean of 1.2 (± 1.3).…”

“…Only two studies [ 28 , 36 ] reported data on body mass index, with a mean of 24.2 (± 0.9) kg/m 2 . The mean Disease Activity Score for 28 joints (DAS28) score was reported by three trials [ 36 , 38 , 39 ] with scores ranging from 4.5 to 5.4 (mean 5.2 [± 0.4]), while only one study [ 40 ] provided data on the basal ACR functional class with a mean of 1.2 (± 1.3). Most subjects (921, 87.2%) were seropositive for rheumatoid factor (RF+), with percentages of RF + participants ranging from 30.4 to 85.0% among included studies.…”