Background/Purpose: Janus kinase (JAK) inhibitors are being evaluated for treatment of active rheumatoid arthritis (RA). The efficacy of upadacitinib (UPA), a selective JAK inhibitor, in improving patient-reported outcomes (PROs) has been demonstrated.¹ These analyses evaluated the long-term benefits of UPA on PROs in patients with active RA.

Methods: M13-538 (NCT02049138) is an ongoing, Phase 2 open-label extension study designed to assess long-term efficacy and safety of UPA in RA patients who completed BALANCE I and BALANCE II randomized controlled trials (RCTs) where doses of 3, 6, 12 and 18 mg BID were evaluated. All eligible patients received UPA 6 mg bid within 30 days of completing either RCT. At weeks 6 and 12, patients with <20% improvement from baseline in tender (TJC) and swollen joint counts (SJC) received a dose increase to 12 mg bid UPA. After 6 weeks on 12 mg bid, patients failing to achieve ≥20% improvement in TJC and SJC discontinued treatment. After week 6, at the discretion of the investigator, the dose could be titrated to 12 mg bid for patients who did not meet low disease activity as defined by the Clinical Disease Activity Index. Continuing patients were divided into 3 cohorts: those who remained on 6 mg bid (never titrated); who increased to and remained on 12 mg bid (titrated up); and who increased to 12 mg bid and subsequently reduced to 6 mg bid only for a safety concern or intolerability (titrated up and down). PROs included: Patient’s Global Assessment of Disease Activity (PtGA), Pain by Visual Analog Scale (Pain VAS), Health Assessment Questionnaire – Disability Index (HAQ-DI), FACIT – Fatigue Scale (FACIT-F), Work Instability Score for Rheumatoid Arthritis (RA-WIS), and EuroQoL-5D (EQ-5D). For this interim analysis, data collected on or before January 13, 2017 were analyzed. Mean changes from baseline and 95% confidence intervals (CI) were calculated for each PRO at week 48.

Results: 493 patients received UPA. Across cohorts, mean age was 53–56 years, 78%–87% were female, and mean duration of RA 8.6–9.5 years. The total patient population exposure to UPA was 725.1 patient-years; with 78% of patients having exposure of ≥12 months and 72% having exposure of ≥18 months. At week 48, patients within all cohorts reported improvements across all PROs (Table). The majority of patients who never titrated dose reported the largest improvements from baseline across PROs at week 48, followed by those who titrated up or up and down.

Conclusion: Patients treated with UPA maintained clinically meaningful improvements in disease activity, pain, physical functioning, fatigue, work functioning, and overall health status till week 48.

Reference

1. Strand V et al. Poster SAT0217. EULAR, Madrid, Spain, 2017.