P1149 Guselkumab improves health-related quality of life as measured by PROMIS-29 in participants with moderately to severely active Crohn’s disease: Phase 3 GRAVITI study
Authors: Sands B , Danese S , Cao Q , Steinwurz F , Kierkus J , Han C , Olurinde M , Yang Z , Merrall E , Terry N A , Hart A 
Published: January 2025

Abstract

Background
Patients (pts) with Crohn’s disease (CD) suffer from symptoms that impair health-related quality of life (HRQoL).1-3 The Phase 3 GRAVITI treat-through trial evaluated the efficacy and safety of SC induction and maintenance of guselkumab (GUS), an interleukin (IL)-23 p19 subunit antagonist, in pts with moderately to severely active CD who had demonstrated a history of inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Here we report HRQoL as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 through Week (Wk) 48. PROMIS-29 consists of 7 domains (symptom domains: anxiety, depression, fatigue, pain interference, and sleep disturbance; functional domains: physical function and social participation) and a pain intensity item.

Methods
The GRAVITI programme for GUS in CD (NCT05197049) employs a treat-through design in which pts were allocated 1:1:1 to GUS 400mg SC every 4 weeks (q4w) (x3)→GUS 200mg SC q4w, GUS 400mg SC q4w (x3)→GUS 100mg SC every 8 weeks (q8w), or placebo (PBO). Pts in the placebo group who met the criteria for rescue therapy received guselkumab 400 mg SC at Wk16, Wk20, and Wk24 followed by guselkumab 100 mg SC q8w; GUS pts stayed on GUS per treat-through design (sham rescue). PROMIS-29 uses standardized T-scores, with a general population mean of 50 and standard deviation (SD) of 10. The physical component summary (PCS) and mental component summary (MCS) scores were calculated based on the domain T-scores. Clinically meaningful improvement (CMI) was according to previously defined thresholds for each domain, and the MCS and PCS.4 Higher scores indicate better health outcomes for the functional domains and two summary scores (PCS and MCS), and worse symptoms for the symptom domains, including the pain intensity item, which uses a numeric rating scale (NRS; 0 [no pain] to 10 [worst pain]).

Results
In the full analysis population, baseline mean PROMIS-29 domain scores were similar among all treatment groups in functional domain scores, symptom domain scores, and pain intensity scores. All baseline values were indicating impaired HRQoL (Table 1). GUS-treated pts achieved a greater improvement from baseline at Wk12 and Wk48 in each domain T-score, the pain intensity NRS score, and the PCS and MCS than PBO-treated pts. Additionally, the percentage of pts achieving CMI through Wk12 and Wk48 was greater for GUS vs PBO in each domain, the pain intensity NRS score, and the PCS and MCS scores (Figure 1).

Conclusion
Pts with moderately to severely active CD treated with GUS SC induction and maintenance experienced broad and clinically meaningful improvements in HRQoL compared with placebo pts as measured by PROMIS-29 through Wk12 and through Wk48.

References
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2.Moradkhani A, Beckman LJ, Tabibian JH. Health-related quality of life in inflammatory bowel disease: psychosocial, clinical, socioeconomic, and demographic predictors. J Crohns Colitis. 2013;7(6):467-473.
3.Kalafateli M, Triantos C, Theocharis G, et al. Health-related quality of life in patients with inflammatory bowel disease: a single-center experience. Ann Gastroenterol. 2013;26(3):243-248.
4.Sands BE, Panés J, Feagan BG, et al. Qualitative and psychometric evaluation of 29-item Patient-Reported Outcomes Measurement Information System® to assess general health-related quality of life in patients with moderately to severely active inflammatory bowel disease. Value Health. 2024;27(9):1225-1234