Redefining Initial Rheumatoid Arthritis Treatment: Tofacitinib Outperforms Methotrexate in Disease Control-An Open-Label Randomized Controlled Trial.

OBJECTIVE

To evaluate the efficacy, safety, and cost-effectiveness of tofacitinib (TOFA) monotherapy vs methotrexate (MTX) with glucocorticoid bridging in disease-modifying antirheumatic drug-naive patients with rheumatoid arthritis (RA).

METHODS

In this open-label randomized controlled trial conducted from July 1, 2021, to December 31, 2023, we enrolled patients with moderate to high RA disease activity to receive TOFA (5 mg twice daily) or MTX (10 to 20 mg weekly with a single intramuscular betamethasone injection) in a 1:1 ratio. The primary end point was the proportion achieving clinical improvement at 3 months (>50% reduction in Simplified Disease Activity Index [SDAI] or absolute SDAI decrease ≥10 points). Secondary outcomes included remission or low disease activity rates, disease activity score changes, adverse events, and cost-effectiveness analysis.

RESULTS

There were 116 patients enrolled, 57 in the TOFA group and 59 in the MTX group. The TOFA group demonstrated significant clinical improvement rates compared with the MTX group at month 3 (94.1% vs 75%; P=.02). The TOFA group demonstrated significantly greater reductions in all disease activity scores at month 3, including SDAI (15.7 [9.2 to 26.9] vs 8.9 [5.1 to 20.5]; P=.02), Clinical Disease Activity Index (14.5 [7.0 to 16.0] vs 7.3 [4.0 to 16.3]; P=.02), Disease Activity Score 28-C-reactive protein (1.7 [1.1 to 2.5] vs 1.2 [0.5 to 2.0]; P=.02), and Disease Activity Score 28-erythrocyte sedimentation rate (2.2 [1.5 to 3.3] vs 1.7 [0.7 to 2.4]; P=.02). The safety profiles were similar between the groups. Tofacitinib exhibited superior cost-effectiveness compared with MTX combined with betamethasone.

CONCLUSION

In disease-modifying antirheumatic drug-naive patients with RA, TOFA monotherapy showed superior early efficacy compared with MTX plus glucocorticoid bridging, with better cost-effectiveness and comparable safety, supporting TOFA as a potential first-line bridging option.

TRIAL REGISTRATION: ChiCTR2100048185.