POS1029 GUSELKUMAB-TREATED PATIENTS WITH PSORIATIC ARTHRITIS ACHIEVED CLINICALLY MEANINGFUL IMPROVEMENTS IN GENERAL HEALTH OUTCOMES MEASURED WITH PROMIS-29 THROUGH 52 WEEKS: RESULTS FROM THE PHASE 3 DISCOVER-1 TRIAL
Authors: A. M. Orbai, L. C. Coates, A. Deodhar, P. Helliwell, C. T. Ritchlin, A. Kollmeier, E. C. Hsia, X. L. Xu, S. Sheng, Y. Jiang, Y. Liu, C. Han
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the DISCOVER-1 study, the interleukin-23 p19 subunit inhibitor guselkumab (GUS) demonstrated robust efficacy across joint and skin clinical manifestations of psoriatic arthritis (PsA). 1 Patients (pts) with PsA also experience a broad range of symptoms that negatively impact health-related quality of life (eg, pain, fatigue, anxiety, depression, sleep disturbance, poor physical function). 2 Objectives: Assess the treatment effect of GUS on general health outcomes in pts with PsA in the DISCOVER-1 trial through Week (W) 52 using the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) instrument. Methods: Pts with active PsA (≥3 swollen + ≥3 tender joints; C-reactive protein ≥0.3 mg/dL) and inadequate response to standard conventional therapies were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). PBO pts switched to GUS 100 mg Q4W at W24. PROMIS-29 contains 4 items for each of 7 domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, social participation) and 1 pain intensity item; 28 items are scored on a 5-point Likert-type scale, and pain intensity is rated from 0-10. The raw score of each domain is converted to a standardized T-score, with norms based on a general population mean score=50 and a standard deviation (SD)=10. Higher scores in anxiety, depression, fatigue, pain interference, and sleep disturbance indicate more severe symptoms; higher physical function and social participation scores indicate better health outcomes. Changes ≥5 points (1/2 SD of T-score) are considered clinically meaningful. Analyses were performed using both observed (mean scores/changes, effect sizes) and imputed (clinically meaningful response, whereby change from baseline was set to 0 at W24/52 for pts who had missing data or at W24 for pts who met treatment failure criteria prior to W24). Results: At baseline, mean PROMIS-29 T-scores for physical function, social participation, sleep disturbance, pain, and fatigue were worse in the 381 PsA pts enrolled in DISCOVER-1 than in the general US population. Across all 7 domains, observed mean PROMIS-29 T-scores showed improvements in GUS-treated pts from baseline to W24 and W52 (Figure 1). Observed mean changes from baseline to W24 and W52, with calculated effect size, are shown (Table 1). In all pts, including those with imputed data, significantly higher percentages of pts in both GUS treatment groups vs PBO had ≥5-point improvements in fatigue, pain interference, physical function, sleep disturbance, social participation, and pain intensity domains at W24 (all nominal p&lt;0.05). Mean improvements in PROMIS-29 domains were maintained through W52. Conclusion: In pts with active PsA, PROMIS-29 results indicate that GUS treatment was associated with clinically meaningful reductions in fatigue and pain and improvement in physical function and social participation, which were maintained through 1 year. References: [1] Deodhar A et al. Lancet. 2020;395:1115-25. [2] Orbai A et al. Ann Rheum Dis. 2017;76:673-80. Table 1. Mean Change and Effect Size of Change From Baseline in PROMIS-29 Domain Scores at W24 and W52 (Observed) Mean Change From Baseline [Effect Size] GUS Q4W GUS Q8W PBO W0-24 GUS Q4W W24-52 W24 W52 W24 W52 W24 W52 Anxiety −3.1 [−0.3] −3.1 [−0.3] −3.7 [−0.4] −4.3 [−0.5] −1.5 [−0.2] −3.6 [−0.4] Depression −2.7 [−0.3] −3.0 [−0.4] −4.0 [−0.4] −4.0 [−0.4] −0.6 [−0.1] −2.5 [−0.3] Fatigue −4.8 [−0.5] −5.6 [−0.6] −4.8 [−0.5] −6.8 [−0.7] −2.1 [−0.2] −5.7 [−0.6] Pain interference −5.4 [−0.8] −6.2 [−1.0] −5.8 [−1.0] −7.0 [−1.1] −2.8 [−0.4] −6.3 [−1.0] Physical function 5.0 [0.8] 5.9 [0.9] 4.1 [0.6] 5.0 [0.7] 1.7 [0.2] 4.2 [0.6] Sleep disturbance −2.5 [−0.4] −3.9 [−0.6] −3.8 [−0.6] −4.4 [−0.6] −1.5 [−0.2] −3.3 [−0.5] Social participation 4.2 [0.5] 5.3 [0.7] 5.3 [0.6] 6.6 [0.8] 1.7 [0.2] 4.9 [0.6] Pain intensity* −2.3 [−1.2] −2.8 [−1.5] −2.1 [−1.1] −2.7 [−1.4] −0.7 [−0.4] −2.5 [−1.3] *Raw score; all other domains reported as T-score. Disclosure of Interests: Ana-Maria Orbai Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: Abbvie, Janssen, and Pfizer, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB Pharma, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Yan Liu Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Chenglong Han Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC.