Clinical efficacy of JAK inhibitors for RA patients with poor-prognosis factors: the ANSWER cohort study

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OBJECTIVES: We evaluated the efficacy of Janus kinase inhibitors (JAKis) compared with TNF inhibitors (TNFis) in RA patients with poor-prognosis factors (PPFs), including ACPA or RF positivity, Clinical Disease Activity Index (CDAI) ≥22, CRP ≥0.6 mg/dl and HAQ-DI ≥0.5. We focused on treatment continuation, disease control and glucocorticoid (GC) reduction. METHODS: We conducted a retrospective analysis of the ANSWER cohort, including 1794 RA patients treated with a TNFi (n = 1235) or JAKi (n = 559). Propensity score matching was applied to reduce bias. We categorized the patients into those with 4PPFs or <4 PPFs. Treatment persistence, CDAI changes and GC tapering over 24 months were analysed. RESULTS: JAKi treatment demonstrated greater CDAI reduction (JAKi vs TNFi median: -23.3 vs -19.9), particularly in ACPA-positive patients. In the 4PPFs patients, JAKi treatment led to a significantly higher low disease activity achievement rate compared with TNFi (68.8% vs 60.9%) at 24 months. JAKi treatment also enabled faster GC tapering, with 72.4% discontinuation compared with 50.3% in the TNFi group at 24 months. Among the 4PPFs patients, JAKi treatment facilitated a greater (but nonsignificant) reduction in GC dosage over time. The cumulative GC discontinuation rate remained consistently higher in the JAKi group, reaching 61.3% vs 48.4% in the TNFi group at 24 months. CONCLUSIONS: JAKi treatment provided sustained disease control (especially in high-risk RA patients) and promoted GC reduction. Although TNFi remains a standard option, JAKi treatment may be preferable in patients with 4PPFs. Further research should evaluate JAKi treatment's long-term safety and efficacy.

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