Authors: Philip Conaghan, Stanley Cohen, Gerd Burmester, Eduardo Mysler, Peter Nash, Yoshiya Tanaka, William Rigby, Jayeshkumar Patel, Tim Shaw, Keith A. Betts, Pankaj Patel, Jianzhong Liu, Rochelle Sun & Roy Fleischmann
Abstract
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).
Key Summary Points |
Why carry out this study?Rheumatoid arthritis (RA) is a chronic and highly debilitating disease that can lead to irreversible joint damage, loss of physical function, and reduced quality of life if not properly treated. There are patients who experience an inadequate response or intolerance to treatment with methotrexate (MTX) and/or to second-line treatment with biologic therapies, such as the tumor necrosis factor alpha inhibitor, adalimumab (ADA); inhibitors of Janus kinase, such as upadacitinib (UPA), could help to address this unmet need. Utilizing data from the phase III randomized, double-blind SELECT-COMPARE trial, this analysis employed a number needed to treat and number needed to harm methodology to evaluate the benefit and risk of UPA versus ADA at weeks 26, 48, and 156 among patients with active RA despite continued therapy with MTX. |
What was learned from the study?UPA showed greater efficacy compared to ADA for the achievement of meaningful clinical and functional improvements at 26, 48, and 156 weeks, with a similar safety profile to ADA (with the exception of an additional safety risk of herpes zoster when compared to ADA). When conducting a benefit–risk assessment among a hypothetical cohort of 100 patients, the present analysis estimated a greater number of patients who would experience benefit rather than harm from UPA treatment in comparison with ADA at 26, 48, and 156 weeks. Given the favorable benefit–risk profile of UPA compared to ADA in the present study, UPA could be considered as an effective and generally safe treatment option for patients with active RA receiving background MTX. |