AB0813 GUSELKUMAB-TREATED PATIENTS ACHIEVED CLINICALLY MEANINGFUL IMPROVEMENT IN SYSTEMIC SYMPTOMS AS MEASURED WITH PROMIS INSTRUMENT: RESULTS FROM PHASE-3 PSORIATIC ARTHRITIS TRIAL DISCOVER 1
Authors: A. M. Orbai, L. C. Coates, A. Deodhar, P. Helliwell, C. T. Ritchlin, A. Kollmeier, E. C. Hsia, X. L. Xu, S. Sheng, B. Zhou, C. Han
Journal: Annals of the Rheumatic Diseases (2020)

Background: Patients (pts) with psoriatic arthritis (PsA) experience broad systemic symptoms including pain, fatigue, depression, sleep disturbance, poor physical function, and diminished social participation. Objectives: DISCOVER 1 is a Phase 3 trial ( NCT03162796 ) evaluating the efficacy and safety of guselkumab (GUS), an anti-interleukin 23 inhibitor that binds to the p19-subunit of IL-23, in pts with active PsA. PROMIS-29 (Patient-Reported Outcomes Measurement Information System-29), a validated generic health instrument, 1 assessed the treatment effect of GUS on symptoms in pts with PsA. Methods: Pts with active PsA despite nonbiologic DMARDs were enrolled, and ~30% of pts could have previously received ≤2 TNFi. Pts were randomized (1:1:1) to subcutaneous GUS 100 mg at Week 0 (W0), W4 then q8W (n=127), GUS 100 mg q4W (n=128), or PBO (n=126). Concomitant stable use of select csDMARDs, oral steroids, and NSAIDs was allowed. PROMIS-29 consists of 7 domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Social Participation) and a pain intensity 0-10 numeric rating scale (NRS). The raw score of each domain is converted into a standardized T-score with a mean of 50 (general population mean) and a standard deviation (SD) of 10. Higher PROMIS scores represent more of the concept being measured. A &gt;= 5-point improvement (1/2 SD of T-score) is defined as clinically meaningful. 1 Results: At baseline, mean PROMIS-29 T-scores for physical function, social participation, sleep disturbance, pain, and fatigue were worse than the general US population. At W24, GUS q8W-treated pts achieved greater improvements from baseline in all PROMIS-29 domains vs PBO (p&lt;0.05) (Table and Fig 1). Results were consistent in the GUS q4W group except for anxiety and sleep disturbance. More pts receiving GUS achieved clinically meaningful improvement vs PBO except for depression and anxiety in the GUS q4W group, which were numerically improved (Fig 2). Conclusion: Active PsA pts treated with GUS achieved clinically meaningful reduction in symptoms and improvement in physical function and social participation vs PBO at W24. References: [1]http://www.healthmeasures.net/score-and-interpret/interpret-scores/meaningful-change/165-meaningful-change Table. PROMIS-29 Domain T-Scores Least Square (LS) Mean Change from Baseline LS Mean Change from Baseline PBO GUS q8W GUS q4W Anxiety -1.37 -3.23* -2.92 Depression -0.85 -3.4** -2.67* Fatigue -1.86 -4.79** -5.08** Pain interference -2.30 -5.49** -5.69** Physical function 1.34 3.89** 5.05** Sleep disturbance -1.17 -3.48** -2.46 Social participation 1.45 4.90** 4.52** Pain intensity -0.56 -1.98** -2.32** Nominal p-values vs placebo: *&lt;0.05, **&lt;0.01 Acknowledgments: None Disclosure of Interests: Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Laura C Coates: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Philip Helliwell: None declared, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Elizabeth C Hsia Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Xie L Xu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Shihong Sheng Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Bei Zhou Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Chenglong Han Employee of: Janssen Research &amp; Development, LLC