Early Guselkumab PsA Response Linked to Long-Term Quality of Life Improvement

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Post-hoc analysis from DISCOVER-2 show patients who achieve a clinical response by week 8 generally go on to see quality-of-life improvements past 1 year.

Early response to guselkumab may be a clear indicator for long-term health-related quality of life improvement among treated patients with psoriatic arthritis (PsA), according to new research.

In new data presented at the Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting in Destin, FL, this week, a multinational team of investigators reported an association between 8-week clinical response to guselkumab and significant improvement to health-related quality of life through approximately 2 years among patients with PsA. The findings elucidate a viable predictor for long-term benefit with the interleukin-23 (IL-23) inhibitor.

Led by Prof. Iain B. McInnes, of the School of Infection & Immunity at University of Glasgow, investigators sought to determine whether early clinical improvement of PsA with guselkumab could serve as an indicator for future patient improvement in measures of quality of life.

“Patients with PsA experience lower quality of life than both the general population and patients with psoriasis alone,” McInnes and colleagues wrote. “Recent PsA treatment recommendations highlight the importance of maximizing long-term health-related quality of life and social participation as primary goals of therapy.”

The team used data from the pivotal phase 3 DISCOVER-2 trial for their analysis. DISCOVER-2 included adult patients with active PsA who were naïve to biologic or Janus kinase (JAK) inhibitors. The trial randomized 739 patients 1:1:1 to either guselkumab 100 mg every 4 weeks (n = 235); guselkumab at baseline, week 4, then every 8 weeks (n = 248); or placebo (n = 246). For their post-hoc analysis, McInnes and colleagues pooled data from the 2 guselkumab treatment arms.

Early clinical improvement with guselkumab was defined as any of the following at 8 weeks:

  • ≥20% improvement in swollen joint count (SJC), tender joint count (TJC), patient pain, patient skin visual analog scale (VAS), and Health Assessment Questionnaire – Disability Index (HAQ-DI)
  • ≥4-point improvement in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) score
  • Minimally clinically important improvement (≥5.7 points) in clinical disease activity in PsA
  • Change in Leeds Enthesitis Index (LEI) and Dactylitis Severity Score (DSS) among patients with baseline enthesitis and dactylitis

The team estimated time-averaged changes in health-related quality of life estimates from baseline to weeks 52 – 100 through a quintet of metrics pertaining to physical and mental benefit. They assessed observed links between early clinical improvement of PsA and long-term health-related quality of life through mixed modeling

Investigators observed a significantly greater improvement in PsA clinical outcomes at week 8 among guselkumab-treated patients versus placebo. What’s more, early clinical improvement was indeed associated with greater increases in health-related quality of life among all early clinical measures except for SJC on the EQ-5D Visual Analog Scale (VAS). Patients who achieved early clinical improvement in any domain aside from DSS and SJC reported improved benefits of mental health-related quality of life between weeks 52- 100.

“Although significantly lower than in patients with early clinical improvement, benefits in health-related quality of life were also observed in patients without clinical improvement at week 8,” investigators noted.

The team concluded that 8-week clinical response with guselkumab—which is significantly improved versus placebo—is linked to significantly greater mental and physical health-related quality of life scores from 1 – 2 years in patients with PsA.

“Although patients without early clinical improvement demonstrated benefits in long-term health-related quality of life, early response in distinct PsA domains differentially impacted more specific aspects of health-related quality of life over 2 years,” they wrote. “In contrast, significantly greater improvements in overall and physical health-related quality of life were observed among responders across several PsA domains.”


McInnes IB, Soriano ER, Tam LS, Shiff NJ, et al. Early Clinical Improvement as Predictor of Long-Term Health-Related Quality of Life in Psoriatic Arthritis Patients Treated with Guselkumab: Post-Hoc Analysis Through 2 Years of a Phase-3 Study. Paper presented at: Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.