A descriptive analysis from the RA UCLouvain Brussels Cohort suggests that combining a tumor necrosis factor inhibitor (TNFi) with a Janus kinase inhibitor (JAKi) may offer a viable treatment strategy for patients with severe, multidrug resistant rheumatoid arthritis (MDR-RA) who have failed multiple biologic and targeted synthetic DMARDs.

The study included 5 patients (3 female, 2 male) with long-standing RA, treated with a TNFi (infliximab or etanercept) in combination with a JAKi (upadacitinib or filgotinib) after failing at least 7 bDMARDs and 2 JAK inhibitors. All patients had also been treated with conventional synthetic DMARDs and glucocorticoids.

“None of the patients suffered from major adverse events due to b/tsDMARDs such as severe infection,” the authors reported. One patient achieved persistent remission for up to 3 years, and 2 additional patients showed a significant reduction in disease activity, reaching remission by their second follow-up. The remaining patients demonstrated improvement in disease control without major safety concerns.

“These preliminary results indicate that a combination therapy of a TNFi and a JAKi provided good clinical results without safety concerns,” the authors concluded. However, they emphasized caution, noting that the risk of infection remains a key consideration. “A b/tsDMARDs combination should be restricted to young patients with a low infection risk and after adequate vaccinations.”

For rheumatologists managing MDR-RA, these findings suggest that TNFi and JAKi combination therapy may represent a therapeutic option offering clinical benefit in a small but challenging patient population that has exhausted standard treatment pathways. Further investigation is needed to confirm long-term safety and efficacy.

Reference
Natalucci F, Van Mullem C, Avramovska A, Sokolova T, Durez P. Combination therapy with TNF inhibitors and JAK inhibitors in multi-drug-resistant rheumatoid arthritis: a case series from the RA UCLouvain Brussels Cohort [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/combination-therapy-with-tnf-inhibitors-and-jak-inhibitors-in-multi-drug-resistant-rheumatoid-arthritis-a-case-series-from-the-ra-uclouvain-brussels-cohort/