Tofacitinib versus methotrexate as the first-line disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis: An open-label randomized controlled trial

Int J Rheum Dis. 2023 Sep;26(9):1729-1736. doi: 10.1111/1756-185X.14801. Epub 2023 Jun 28.


Objective: To compare tofacitinib and methotrexate (MTX) as first-line disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA).

Methods: This open-label, randomized controlled, parallel-group, 3-month trial randomly assigned 100 RA patients to tofacitinib 10 mg daily (49 patients) or MTX 25 mg subcutaneously weekly (51 patients). The primary end point was low disease activity (LDA) measured with Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and the secondary end point was LDA and remission measured by DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Health Assessment Questionnaire Disability Index (HAQ-DI) response and mean reduction of core set of outcomes from baseline at 12 weeks were also analyzed as secondary end points. In addition, acute-phase reactants and composite measurements among groups were examined.

Results: LDA in DAS28-CRP was achieved in 17 (34.7%) tofacitinib patients and 18 (35.3%) MTX patients (p = .95). Fourteen (28.6%) and 11 (21.6%) tofacitinib and MTX patients, respectively, achieved LDA by DAS28-ESR (p = .42). Tofacitinib and MTX groups achieved LDA similarly in CDAI (36.7% against 37.3%; p = .96) and SDAI (38.8% vs. 39.2%; p = .96). There was no significant difference in achieving remission between the groups. At 12 weeks, tofacitinib reduced ESR and CRP (p < .05). Composite measures and functional status decreased within groups but not between groups (p > .05). Five (13.51%) tofacitinib patients developed hypertension. MTX caused gastrointestinal problems in 12 (30%) individuals. Two MTX (5%) and two tofacitinib (5.4%) patients had increased liver enzymes and renal impairment, respectively. Tofacitinib had 5.4% infection compared with 5% for MTX.

Conclusions: As tofacitinib may be more effective than MTX according to previous reports such as the ORAL Start study, high-dose MTX (25 mg/week, subcutaneously) used in this study may be as efficacious as tofacitinib in patients with established RA who were DMARD naive or had not received a therapeutic dose of DMARDs. However, adverse effects differed between groups. Registered on:; ID: NCT04464642.

Keywords: Bangladesh; DMARDs; methotrexate; rheumatoid arthritis; tofacitinib.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / diagnosis
  • Arthritis, Rheumatoid* / drug therapy
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Methotrexate / adverse effects
  • Treatment Outcome


  • Antirheumatic Agents
  • Methotrexate
  • tofacitinib

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