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Clinical Trial
. 2022 Nov;15(6):657-668.
doi: 10.1007/s40271-022-00588-6. Epub 2022 Jun 30.

Meaningful Improvement in General Health Outcomes with Guselkumab Treatment for Psoriatic Arthritis: Patient-Reported Outcomes Measurement Information System-29 Results from a Phase 3 Study

Ana-Maria Orbai  1 , Laura C Coates  2 , Atul Deodhar  3 , Philip S Helliwell  4 , Christopher T Ritchlin  5 , Evan Leibowitz  6 , Alexa P Kollmeier  7 , Elizabeth C Hsia  7   8 , Xie L Xu  7 , Shihong Sheng  7 , Yusang Jiang  7   9 , Yan Liu  7 , Chenglong Han  7
Affiliations
Clinical Trial

Meaningful Improvement in General Health Outcomes with Guselkumab Treatment for Psoriatic Arthritis: Patient-Reported Outcomes Measurement Information System-29 Results from a Phase 3 Study

Ana-Maria Orbai et al. Patient. 2022 Nov.

Abstract

Objective: The Phase 3 DISCOVER-1 study of guselkumab is the first randomized controlled trial to use Patient-Reported Outcomes Measurement Information System (PROMIS) measures to assess the effects of treatment on general health outcomes in patients with psoriatic arthritis (PsA).

Methods: Patients (N = 381) with active PsA were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, then every 8 weeks (Q8W); or placebo with Week 24 crossover to guselkumab Q4W. The PROMIS-29 Profile contains four items for each of seven domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and social participation) and one pain-intensity item. Raw domain scores are converted to standardized T-scores, with norms based on a US general population mean of 50 (1 standard deviation (SD) = 10). T-score changes of ≥ 5 are considered clinically meaningful. Least-squares mean PROMIS-29 T-score changes from baseline to Week 24 and Week 52 were summarized for the guselkumab and placebo groups; nominal p-values comparing results between guselkumab and placebo were calculated at Week 24 using a mixed model for repeated measures. The proportions of patients who achieved clinically meaningful improvement in PROMIS-29 T-scores were also summarized at Week 24 and Week 52; nominal p-values comparing results between guselkumab and placebo were calculated at Week 24 using the Cochran-Mantel-Haenszel test.

Results: In the DISCOVER-1 patient population, mean PROMIS-29 T-scores at baseline were ~ 1 SD worse for physical function and pain interference and were numerically worse for social participation, fatigue, and sleep disturbance compared with the US general population. At Week 24, mean PROMIS-29 T-scores improved in guselkumab-treated patients, approaching US population norms; T-scores continued to improve through Week 52. Significantly higher proportions of patients in both guselkumab treatment arms (31-52% across domains) had clinically meaningful improvements in pain interference, fatigue, physical function, sleep, and social participation at Week 24 versus placebo (all nominal p ≤ 0.05).

Conclusion: In patients with active PsA, guselkumab treatment provided clinically meaningful reductions in fatigue and pain and improvement in physical function and social participation, as measured by the PROMIS-29 Profile. These improvements were maintained through 1 year.

Clinicaltrials: GOV: Registration number, NCT03162796; Submission date 19 May 2017.

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Conflict of interest statement

Ana-Maria Orbai has received grant/research support from AbbVie, Amgen, Eli Lilly and Company, Celgene, Novartis, Janssen, and Horizon; has received consulting fees from Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, and is also 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 has received grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; speaker fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer, and UCB; and consultant fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Laura C Coates is funded by a National Institute for Health Research (NIHR) Clinician Scientist award. The research was supported by the NIHR Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. We acknowledge the support of the NIHR Clinical Research Network. Atul Deodhar has received consulting fees for participation in Advisory Boards from AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB; grant/research support from AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB; and speaker fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Philip S. Helliwell has received consulting fees from Eli Lilly and fees for educational services from AbbVie, Amgen, Novartis, and Janssen. Christopher T. Ritchlin has received grant/research support from UCB Pharma, AbbVie, and Amgen; consulting fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, and Janssen. Evan Leibowitz is an employee of Janssen Scientific Affairs, LLC, and owns stock in Johnson & Johnson, of which Janssen Scientific Affairs is a wholly owned subsidiary. Alexa P. Kollmeier, Elizabeth C. Hsia, Xie L. Xu, Shihong Sheng, Yan Liu, and Chenglong Han are employees of Janssen Research & Development, LLC, and own stock in Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary. Yusang Jiang is a consultant employed by Cytel, Inc. and funded by Janssen to provide statistical support.

Figures

Fig. 1
Fig. 1
Mean PROMIS-29 T-scores (observed data). The red circles indicate US population norm values of 50 for all domains. For the anxiety, depression, fatigue, pain interference, and sleep disturbance domains, higher scores indicated more severe symptoms. For the physical function and social participation domains, higher scores indicate better health outcomes. GUS guselkumab, PBO placebo, PROMIS Patient-Reported Outcomes Measurement Information System, Q4W every 4 weeks, Q8W every 8 weeks
Fig. 2
Fig. 2
Cumulative distribution of points of improvement in PROMIS-29 domain physical function (A), pain interference (B), social participation (C), and fatigue (D) T-scores from baseline to Week 24. PROMIS Patient-Reported Outcomes Measurement Information System, Q4W every 4 weeks, Q8W every 8 weeks
Fig. 3
Fig. 3
Achievement of ≥ 5-point improvements in PROMIS-29 domain T-scores from baseline to Week 24 and 52. Week 24: All patients, including those with imputed data (patients meeting treatment failure prior to Week 24 or with missing data at Week 24 were considered as not achieving ≥5-point improvement); P-values calculated using Cochran-Mantel-Haenszel test; nominal p-values vs. PBO: *p < 0.05; †p < 0.01; ‡p < 0.001. GUS Q4W, n = 128; GUS Q8W, n = 127; PBO, n = 126. Week 52: Evaluable patients; after discontinuation of study agent for any reason, patients with missing data were considered non-responders. GUS guselkumab, PBO placebo, PROMIS Patient-Reported Outcomes Measurement Information System, Q4W every 4 weeks, Q8W every 8 weeks
Fig. 4
Fig. 4
Absolute values of effect size for change from baseline in PROMIS-29 T-scores. GUS guselkumab, PBO placebo, PROMIS Patient-Reported Outcomes Measurement Information System, Q4W every 4 weeks, Q8W every 8 weeks
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