2111: Long-term Efficacy of Guselkumab in Fatigue and Identification of Early Treatment Targets: Post Hoc Analysis Through 2 Years of a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis

Dafna Gladman¹, Michael Starr², Roberto Ranza³, Ana-Maria Bravo Perdomo⁴, Marcie Strauss⁵, May Shawi⁶, Chenglong Han⁷, Emmanouil Rampakakis⁸, Andrew Ostor⁹ and Philip J Mease¹⁰, ¹Toronto Western Hospital, Schroeder Arthritis Institute, Toronto, ON, Canada, ²Montreal General Hospital, Montréal, QC, Canada, ³Serviço de Reumatología, Universidade Federal de Uberlândia, Uberlândia, Brazil, ⁴Immunology Medical Affairs, Janssen Latin America, Columbia, Colombia, ⁵Medasource, Indianapolis, IN, ⁶Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, ⁷Immunology, Janssen Research & Development, LLC, Spring House, PA, ⁸McGill University, Department of Pediatrics and JSS Medical Research, Montréal, QC, Canada, ⁹Cabrini Medical Centre, Monash University & Emeritus Research, Melbourne, Australia, ¹⁰Swedish Medical Center/Providence St. Joseph Health, Seattle, WA

Background/Purpose: The IL-23p19-subunit inhibitor guselkumab (GUS) demonstrated clinically meaningful improvements in fatigue through one year of treatment¹ independent of its effects on ACR20 and MDA achievement². In this post hoc analysis, the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale was used to: (a) evaluate the long-term effect of GUS in maintaining improvements in or further improving fatigue between week (W) 52 and W100, and to; (b) identify potential early (W8) predictors, in terms of fatigue, for improved long-term fatigue outcomes.

Methods: DISCOVER-2 enrolled adult patients (pts) with active PsA (≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dl) who were naïve to biologics/JAK inhibitors. Pts were randomized (1:1:1) and treated with GUS 100 mg every 4W (Q4W); GUS 100mg at W0, W4, then Q8W; or placebo (PBO→GUS Q4W; crossing over to GUS Q4W at W24). Pts with baseline (BL) fatigue levels lower than the normative value (FACIT-F score ≤43)³ were included in these post hoc analyses (N=681). The proportions of pts with clinically meaningful improvement (≥4 points) from BL in FACIT-F and with normative FACIT-F levels between W52 and W100 were calculated using non-responder imputation (NRI) for missing data and compared over time within each treatment group with the McNemar test. Changes in FACIT-F over time were assessed with mixed models adjusting for time, treatment group, their interaction, and BL FACIT-F score. Receiver operating characteristics (ROC) analyses were conducted using Youden's index to determine optimal cutoffs at W8 for predicting achievement of normative scores and clinically meaningful FACIT-F responses at W100.

Results: At BL, the mean (SD) FACIT-F score was 28.3 (8.7) with similar levels across treatment groups. At W52, 66.1%, 69.6%, 68.0%, and 67.8% of pts in the PBO→GUS Q4W, GUS Q4W, GUS Q8W, and pooled GUS groups, respectively, achieved clinically meaningful improvements from BL in FACIT-F score; response rates were maintained through W100 (Figure 1a). Normative FACIT-F levels were achieved by 24.9%, 28.1% 29.4% and 27.5% of pts in each treatment group, respectively, at W52, and by increasingly greater proportions of pts through W100 (Figure 2b). Significant improvements from BL in FACIT-F scores were observed at W52 (all nominal p< 0.05), with further improvements seen from W52 to W100 across all GUS groups (Figure 2). ROC optimal cutoff in FACIT-F improvement from BL to W8 associated with a clinically meaningful improvement in FACIT-F at W100 was ≥2.0 (nominal p< 0.0001); while for achieving normative FACIT-F levels at W100, the optimal cutoff in actual FACIT-F score at W8 was ≥39.5 (nominal p< 0.0001) (Figure 3).

Conclusion: The clinically meaningful improvements in fatigue seen after 1 year of GUS treatment were further enhanced through 2 years, at which time nearly a third of GUS-treated pts reported normative FACIT-F levels. Early targets in FACIT-F levels achieved with GUS were identified to aid in guiding treatment decisions in routine clinical practice.

References:
1. Ritchlin CT et al. RMD Open. 2022 Mar;8(1);e002195.
2. Rahman P et al. Arthritis Res Ther. 2021 Jul 14;23(1):190.
3. Montan I et al. Value Health. 2018 Nov;21(11):1313-1321.





Disclosures: D. Gladman, AbbVie, Amgen, Eli Lilly, Janssen, Gilead, Novartis, Pfizer, Bristol-Myers Squibb(BMS), Galapagos, UCB Pharma, Celgene; M. Starr, Janssen, Pfizer, Novartis, Eli Lilly, AbbVie/Abbott, UCB; R. Ranza, AbbVie, Janssen, Novartis, Pfizer; A. Bravo Perdomo, Janssen, Johnson & Johnson; M. Strauss, Medasource, Janssen; M. Shawi, Janssen Pharmaceutical Companies of Johnson and Johnson; C. Han, Janssen Research and Development, LLC, Johnson & Johnson; E. Rampakakis, Janssen, JSS Medical Research; A. Ostor, AbbVie, Pfizer, Novartis, Bristol-Myers Squibb(BMS), Eli Lilly, Janssen, Roche, Gilead, Paradigm, UCB; P. Mease, AbbVie, Amgen, Janssen, Novartis, Pfizer Inc, UCB, Sun Pharma, Eli Lilly, Bristol-Myers Squibb(BMS), Celgene, Genentech.