Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA).

Methods: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles.

Results: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA.

Conclusion: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).