Background/Purpose: Patient-reported outcomes (PROs) in RA are important to evaluate total disease impact, although treatment decisions may often be guided by traditional physician-derived measures of disease activity. The purpose of this analysis was to determine the association between PROs and composite outcomes in RA patients receiving the JAK1-selective inhibitor, upadacitinib (UPA), with prior inadequate responses (IR) to conventional synthetic (cs) or biologic (b) DMARD(s).

Methods: Data were analyzed from two 12-week (wk), phase 3, RCTs in csDMARD-IR (SELECT-NEXT) and bDMARD-IR (SELECT-BEYOND) patients receiving UPA 15 or 30 mg daily (QD) or placebo and background csDMARD therapy; as well as from a third trial (SELECT-MONOTHERAPY), in which MTX-IR patients received UPA monotherapy or MTX (blinded) for 14 wks. Moderate and substantial improvements in pain (≥30% and ≥50% improvement from baseline [Δ BL], respectively), and normative values in HAQ-DI (≤0.25) and functional assessment of chronic illness therapy-fatigue (FACIT-F: ≥43.6, SELECT-NEXT only) were evaluated. Associations between clinical outcomes (total and swollen joint counts [TJC, SJC], physician global assessment [MDGA], CRP and composite measures [ACR, DAS28-CRP, CDAI]), and PROs (pain [VAS], HAQ-DI, patient global assessment [PtGA], morning stiffness, FACIT-F) were evaluated through Pearson correlations and a univariate logistic model, controlling for treatment group and BL value.

Results: Patients enrolled in the SELECT-NEXT and SELECT-BEYOND trials had moderate to severely active RA (mean DAS28-CRP: 5.6 and 5.8, respectively), with disease durations of 7 and 12 years, respectively. In general, ΔBL in pain and HAQ-DI scores were marginally correlated with individual physician-derived measures (SELECT-NEXT: pain, 0.161-0.537, HAQ-DI, 0.081-0.425; SELECT-BEYOND: pain, 0.131-0.511, HAQ-DI, 0.052-0.409); moreover, moderate to high correlations were observed between pain, HAQ-DI and PtGA in both RCTs (SELECT-NEXT: pain, 0.835-0.851, HAQ-DI, 0.418-0.518; SELECT-BEYOND: pain, 0.828-0.871, HAQ-DI, 0.479-0.520). In regression analyses, improvements in individual disease assessments were associated with significant improvements in pain at Wk12 across RCTs (Table). In addition, patients with improvement in composite measures were more likely to report substantial improvements in pain. Similar associations were evident for HAQ-DI scores at Wk12 across RCTs (including SELECT-MONOTHERAPY), as well as for FACIT-F in SELECT-NEXT.

Conclusion: Achieving substantial improvements in pain, physical function, and fatigue was associated both with individual physician-derived measures and with composite disease outcomes. These data support the use of PROs in RCTs and also imply that, although PROs may be included in composite endpoints, they are distinct parameters that provide additional insights into the true impact of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-between-patient-reported-outcomes-and-clinical-measures-among-rheumatoid-arthritis-patients-analyses-using-phase-3-clinical-trials-of-upadacitinib/