Combination therapy with JAK inhibitors and TNF inhibitors in severe refractory rheumatoid arthritis: A monocentric case series.

BACKGROUND

A subset of patients with rhe umatoid arthritis (RA) remains refractory despite sequential use of conventional synthetic and biological/targeted synthetic DMARDs (b/tsDMARDs). For these multi-refractory cases, therapeutic options are limited. Data on the concomitant use of Janus kinase inhibitors (JAKi) and tumor necrosis factor inhibitors (TNFi) are scarce.

OBJECTIVES

To describe our monocentric experience with combination therapy (CoT) using JAKi and TNFi in highly selected patients with severe, long-standing, multi-refractory RA, focusing on clinical response and safety.

METHODS

We conducted a retrospective observational case series at a tertiary rheumatology center. RA adult patients who had failed multiple b/tsDMARDs and received concomitant JAKi and TNFi were included. Clinical, serological, and radiographic characteristics were collected. Disease activity (DAS28-CRP, CDAI, SDAI), patient-reported outcomes, glucocorticoid (GC) use, treatment persistence, and adverse events were assessed.

RESULTS

Six patients with erosive, long-standing RA received CoT after a median disease duration of 192 months and at least five prior b/tsDMARD lines. Combinations included Infliximab, Etanercept or Adalimumab with Upadacitinib or Filgotinib. Four of six patients achieved remission or low disease activity, accompanied by progressive GC tapering and discontinuation in two cases. At 18- and 36-month follow-up (two patients), disease control was maintained without major infections, thromboembolic events, or cardiovascular complications.

CONCLUSIONS

In this small, highly selected cohort of severe multi-refractory RA, JAKi-TNFi combination therapy was associated with meaningful clinical improvement and an acceptable short- to mid-term safety profile. Although not supporting widespread use, our findings suggest that, under strict monitoring and individualized risk-benefit assessment, this strategy may represent a rescue option in exceptional cases. Larger prospective studies are needed to better define efficacy and safety.