Patient-reported outcomes and realistic clinical endpoints for JAK inhibitors in rheumatoid arthritis

Despite many effective therapeutics, health-related quality of life in RA remains low. Patients describe impacts of their disease in differing terms than health-care providers, stressing importance of pain, fatigue, poor sleep, and restrictions in work and social participation.

Patient-reported outcomes (PROs) across the phase 3 randomized controlled trials (RCTs) in RA with the JAK inhibitors (JAKis) are summarized. Patient populations, whether conventional synthetic disease modifying anti-rheumatic drug incomplete responders (csDMARD-IR) or biologic DMARD incomplete responders (bDMARD-IR) or csDMARD-naive, report differing baseline scores and placebo responses, generally lower in more treatment experienced patients. Improvements with all the approved JAKis in RA occur rapidly and are often maximal by 12-14 weeks, continuing thereafter. The rapidity of benefit reported by patients and convenience of oral administration often lead to increased adherence.

A broad variety of PROs utilized in the RA RCTs with the JAKis confirm the clinical meaningfulness of their efficacy across treatment-experienced and naive populations. A majority of patients report statistically significant as well as clinically meaningful (≥ minimum clinically important differences, MCID) improvements, with numbers needed to treat (NNTs) ≤ 10 and scores ≥ normative values at endpoint, despite ≤ 12% reporting such scores at baseline.