Speed of Onset of Effect on Patient- Reported Outcomes Assessed through Daily Electronic Patient Diaries in the Baricitinib Phase 3 RA Clinical Program
Erica Tierney (non-author presenter)1, Peter C. Taylor2, Grace C. Wright3, Carol L. Gaich4, Amy M. DeLozier4, Stephanie de Bono4, Douglas E. Schlichting4, Terence P. Rooney4, Jiajun Liu4, Scott D. Beattie4, and Maxime Dougados5
1Eli Lilly and Company Limited, Lilly Ireland, Dublin, Ireland; 2NDORMs, University of Oxford, Oxford, United Kingdom, 3New York University Langone Medical Center, New York, United States, 4Eli Lilly and Company, Indianapolis, United States, 5Department of Rheumatology, Cochin Hospital, Paris, France
Baricitinib (bari), an oral Janus kinase (JAK) 1/JAK2 selective inhibitor, has demonstrated clinical efficacy with a satisfactory safety profile when administered once daily in 4 completed Phase 3 studies in patients with RA.
In 2 studies, RA-BEAM (52-week study in patients with inadequate response [IR] to MTX) and RA-BUILD (24-week study in patients with IR to conventional synthetic [cs] DMARDs), patients recorded their worst joint pain, duration and severity of morning joint stiffness (MJS), and worst tiredness each day for 12 weeks using electronic diaries. In previous analyses based on weekly averages of daily scores, bari produced significant improvements in patient-reported outcomes (PROs) compared to placebo (pbo) as early as Week 1 and compared to adalimumab (ada) as early as Weeks 2-4. The aim of these analyses was to explore the kinetics of response using daily diary scores without weekly averaging.
PRO data were analyzed by study day after randomization (Day 1) - Day 28 for all treated patients. Mixed models for repeated measures analysis were applied (with MJS duration by nonparametric methods).
Consistent with the original weekly-averaged data, daily diary scores showed significant improvement in patients receiving bari compared to pbo and ada. Improvements relative to pbo were apparent as early as the 3rd day of treatment for MJS severity, worst tiredness, and worst joint pain, and by Day 5 for MJS duration. Improvements relative to ada were apparent as early as Day 19 for MJS severity, Day 21 for worst tiredness, and Day 17 for worst joint pain. The greatest rapidity and magnitude of benefit was seen with the bari 4-mg daily dose.
In this post hoc analysis from Phase 3 studies of patients with RA with inadequate response to MTX or other csDMARDs, treatment with bari produced rapid improvements in PROs compared to pbo and ada, with significant differences appearing within the initial days of treatment.