PATIENTS with rheumatoid arthritis (RA) who stop tumour necrosis factor (TNF) inhibitor treatment may achieve more stable long-term disease control with methotrexate-tacrolimus combination therapy than with methotrexate alone, according to a study published in BMC Rheumatology.
The retrospective cohort study analysed 147 treatment courses in 116 RA patients who had successfully discontinued TNF inhibitors by late 2022. Over a 10-year follow-up period, those on methotrexate-tacrolimus combination therapy experienced significantly fewer treatment failures, less treatment intensification, and fewer disease flares than those on methotrexate monotherapy.
Combination therapy reduced the risk of first flare by 45% (HR 0.55; 95% CI, 0.36–0.84) and the need for additional biologics or Janus kinase inhibitors by 61% (HR 0.39; 95% CI, 0.22–0.71). The benefit was most notable in patients who had previously flared while on methotrexate alone, with hazard ratios dropping as low as 0.04 for key outcomes.
Importantly, no significant differences in treatment-limiting adverse events were observed between the groups. Although tacrolimus users showed a slight annual increase in serum creatinine, the change was minimal, suggesting a low risk of long-term renal damage.
These findings support methotrexate-tacrolimus as a viable and safe option for maintaining remission after TNF inhibitor withdrawal, especially for patients with a history of methotrexate monotherapy relapse. The combination offers a potential strategy for sustaining RA control without the need for continuous biologic therapy.
Reference
Naniwa T, Kajiura M. Long-term effectiveness and safety of methotrexate-tacrolimus combination therapy versus methotrexate monotherapy in reducing rheumatoid arthritis flares after TNF inhibitor discontinuation: a retrospective cohort study. BMC Rheumatol. 2025;DOI: 10.1186/s41927-025-00489-9.
