S799 Health-Related Quality of Life with Guselkumab Induction and Maintenance Therapy as Measured by PROMIS-29: Results Through Week 48 of Phase 2 GALAXI 1 Study

Introduction: Patients (pts) with Crohn’s disease (CD) suffer from symptoms that negatively impact their health related quality of life (HRQoL). In GALAXI 1, a phase 2 study of guselkumab (GUS), a selective IL-23 antagonist, for the treatment of pts with moderately to severely active CD who had inadequate response or intolerance to conventional therapies and/or biologics, HRQoL was evaluated using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Methods: GALAXI has a treat-through design with pts remaining on randomized treatment (GUS or ustekinumab [UST]) through Wk48. Pts were randomized 1:1:1:1:1 into 5 arms for induction: GUS 200, 600, or 1200mg IV at Weeks (Wks) 0, 4, 8; UST ∼6mg/kg IV at Wk0 and 90mg SC at Wk8; or PBO IV. At Wk12, pts transitioned to maintenance: GUS 200mg IVà100mg SC q8w, GUS 600mg IVà200mg SC q4w, GUS 1200mg IVà200mg SC q4w, PBO non-respondersàUST ∼6mg/kg IVà90mg SC q8w, and PBO respondersàPBO SC q4w. UST pts continued 90mg SC q8w. Pts randomized to PBO were not included in the Wk48 analyses. 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 general population mean of 50 and standard deviation (SD) of 10. For physical function and social participation, higher scores indicate better outcomes, while for all other symptom domains like anxiety, higher scores indicate worse outcomes. Clinically meaningful improvement was defined as ≥3-point improvement in pain NRS score and ≥5-point (or 1/2 SD of population) improvement in each domain T-score. Results: Among pts randomized and evaluated in the primary efficacy analysis, mean PROMIS-29 domain scores were similar between treatment groups at baseline with functional domain score < 50 and symptom domain scores >50, indicating impaired HRQoL (Table). Pts treated with GUS had greater improvement in all domain scores at Wk12 compared with PBO. GUS treatment resulted in continued improvement in domain scores from Wk12 to Wk48. GUS-treated pts achieved clinically meaningful improvement in fatigue T-scores (45.9-63.5%), pain interference T-scores (52.5-71.4%) and pain intensity NRS score at Wk48 (56.4-70.2%). Conclusion: Induction and maintenance treatment with GUS was effective in improving HRQoL as measured by PROMIS-29 in pts with moderately to severely active CD at Wk48. Table 1. - Change from baseline at Wk 12 and Wk 48 for PROMIS-29 scores Placebo (N=61) GUS 200 mg IV q4wà100 mg SC q8w (N=61) GUS 600 mg IV q4wà200 mg SC q4w (N=63) GUS 1200 mg IV q4wà 200 mg SC q4w (N=61) UST ∼6 mg/kg IV à90 mg SC q8w (N=63) Anxiety T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 57.68 (10.004), N=57 -0.73 (8.872), N=56 56.43 (9.344), N=60 -4.63 (8.869),* N=58-5.66 (10.437), N=56 56.94 (9.843), N=63 -3.43 (9.178),* N=61-4.85 (8.831), N=58 57.29 (9.455), N=61 -6.78 (7.805),** N=57-6.34 (10.188), N=49 54.25 (9.068), N=63 -3.86 (7.908), N=63-5.09 (6.624), N=59 Depression T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 54.99 (9.386), N=57-0.17 (8.384), N=56 54.33 (9.306), N=60 -4.54 (10.567),** N=58-4.91 (11.899), N=56 53.64 (10.567), N=63 -1.98 (7.123),* N=61-3.33 (8.077), N=58 54.07 (9.499), N=61 -5.48 (6.999),** N=57-5.52 (9.559), N=49 52.20 (8.619), N=63 -3.70 (8.217), N=63-2.86 (7.055), N=59 Fatigue T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 57.80 (9.128), N=57-0.89 (9.640), N=56 56.36 (9.193), N=60 -7.33 (9.320),** N=58-7.59 (10.587), N=56 56.74 (10.097), N=63 -6.30 (9.314)**, N=61-9.53 (9.903), N=58 58.35 (9.361), N=61 -7.27 (8.021),** N=57-8.03 (9.114), N=49 56.03 (8.991), N=63 -5.91 (10.467), N=63-7.44 (9.369), N=59 Pain interference T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 62.25 (6.625), N=57-2.43 (7.811), N=56 60.26 (8.550), N=60 -8.19 (9.467),** N=58-10.71 (10.989), N=56 62.26 (6.337), N=63 -9.29 (8.997),** N=61-13.44 (9.060), N=58 60.69 (7.418), N=61 -6.60 (7.659),** N=57-10.34 (9.568), N=49 60.37 (8.431), N=63 -7.93 (9.854), N=63-7.70 (9.334), N=59 Pain intensity NRS score, a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 5.53 (2.122), N=57-0.84 (2.380), N=56 5.13 (2.012), N=60 -2.41 (2.740),** N=58-3.11 (2.695), N=56 5.49 (1.925), N=63 -2.82 (2.164),** N=61-3.53 (2.494), N=58 5.46 (2.038), N=61 -2.30 (2.420),** N=57-2.88 (2.990), N=49 5.37 (2.238), N=63 -2.21 (2.259), N=63-2.73 (2.420), N=59 Physical Function T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 42.70 (7.491), N=571.24 (8.106), N=56 44.71 (8.391), N=60 4.64 (8.249),* N=585.98 (8.851), N=56 45.24 (7.888), N=63 3.73 (7.053),* N=615.73 (8.242), N=58 43.16 (8.275), N=61 3.40 (8.037),* N=575.18 (8.243), N=49 45.72 (8.056), N=63 3.30 (7.888), N=633.80 (7.307), N=59 Sleep disturbance T-score a ,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 55.06 (8.418), N=57-0.88 (6.833), N=56 54.19 (8.062), N=60 -4.83 (8.489),** N=58-5.36 (8.520), N=56 54.84 (7.181), N=63 -4.05 (5.805),* N=61-6.28 (7.636), N=58 53.23 (7.447), N=61 -4.02 (5.727),** N=57-5.48 (7.018), N=49 52.55 (7.408), N=63 -3.16 (8.143), N=63-4.61 (7.580), N=59 Ability to participate in social roles and activities T-score a,b Baseline, mean (SD)Change from baseline, mean (SD), at: Wk 12 Wk 48 45.50 (7.990), N=570.58 (7.962), N=56 46.25 (9.278), N=60 6.54 (8.867),** N=587.65 (10.842), N=56 46.80 (8.705), N=63 5.18 (8.922),** N=618.56 (9.877), N=58 45.40 (9.329), N=61 5.49 (7.130),** N=577.10 (8.142), N=49 47.99 (8.827), N=63 4.81 (8.364), N=635.44 (8.757), N=59 *Nominal p-value < 0.05 for guselkumab vs placebo at Wk 12.**Nominal p-value < 0.001 for guselkumab vs placebo at Wk 12.aPatients who had a prohibited change in concomitant Crohn’s disease medication, a Crohn’s disease-related surgery, or discontinued study agent due to lack of efficacy or an AE of worsening Crohn’s disease prior to the designated analysis timepoint had their baseline value carried forward from that timepoint onwards. Patients who had discontinued study agent due to any other reasons prior to the designated analysis timepoint had their observed data used, if available, from that timepoint onwards.bPatients who had insufficient data to calculate PROMIS-29 domain score at the designated analysis timepoint did not have their missing data imputed.NOTE: No comparisons between ustekinumab and placebo were made at Wk 12. No treatment comparisons were made at Wk 48. The p-values for the comparisons of each guselkumab treatment group with the placebo group at Wk 12 were based on MMRM analysis including change from baseline in PROMIS-29 domain score as the response; treatment group, visit, baseline PROMIS-29 domain score, BIO-Failure status (yes, no), baseline CDAI stratification (≤300, >300), an interaction term of visit with treatment group and an interaction term of visit with baseline PROMIS-29 domain score as explanatory variables.

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