Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis.

Exposure-response analyses of upadacitinib (UPA) key efficacy and safety end points (3,685 and 4,577 subjects for efficacy and safety, respectively) using data from phase II and phase III rheumatoid arthritis (RA) studies were conducted to support benefit-risk assessment. Percentage of subjects achieving American College of Rheumatology (ACR)20/50/70, disease activity score 28 (C-reactive protein) (DAS28-CRP) ≤ 3.2, and DAS28-CRP < 2.6 increased with increasing UPA plasma exposures. With the small number of observed safety events, no clear trends for exposure-response relationships were identified for pneumonia, herpes zoster infection, changes in platelet count, lymphopenia (Grade ≥ 4), or neutropenia (Grade ≥ 3) up to Week 26. Shallow exposure-response relationships were observed for > 2 g/dL decrease in hemoglobin, lymphopenia Grade ≥ 3 at Week 12/14, and serious infections at Week 24/26. Exposure-efficacy analyses demonstrate that UPA 15 mg q.d. (once daily) dose provided the optimal benefit-risk in RA through maximizing efficacy with only small incremental benefit with 30 mg q.d.; and with consistency across RA subpopulations and with UPA monotherapy or combination with conventional synthetic disease-modifying antirheumatic drugs.

Is the Health Utilities Index 3 valid for patients with ankylosing spondylitis?

OBJECTIVE: To assess the convergent and discriminative validity of the Health Utilities Index Mark 3 (HUI-3) for patients with ankylosing spondylitis (AS). METHODS: Data were derived from the Adalimumab Trial evaluating Long-term efficacy and safety for Ankylosing Spondylitis (ATLAS). The study team specified 90 a priori hypotheses regarding the direction and magnitude of the expected associations between the overall and single-attribute scores of the HUI-3 and other health status and quality-of-life measures: Short Form 36 Health Survey (SF-36), Ankylosing Spondylitis Quality-of-Life Questionnaire, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, and Patient's and Physician's Global Assessments of Disease Activity. With baseline data, correlation coefficients were calculated and interpreted according to the guidelines suggested by Guyatt for negligible (0-0.19), weak (0.20-0.34), moderate (0.35-0.50), and strong (>0.5) associations. The a priori hypotheses were tested using Pearson's correlation coefficients. RESULTS: A total of 315 patients with active AS were randomized and enrolled in ATLAS. The correlation coefficients between the HUI-3 scores and other health-related quality-of-life instruments confirmed 61.1% of the a priori hypotheses, with an additional 35.5% being under- or overestimated by one correlation category. CONCLUSION: These results provide evidence of the cross-sectional, convergent, and discriminative validity of the HUI-3 for deriving utility scores in patients with AS.