Introduction
Resolution of pain, fatigue and other symptoms are key treatment goals for many patients (pts) with Crohn’s disease (CD);1,2 however, time to symptomatic improvement in pts treated with vedolizumab (VDZ) has not been formally evaluated.
Aims & Methods
VOICE (NCT06249555) is a prospective, observational study in pts with CD aged ≥18 years initiating VDZ or anti-IL-23 antagonist treatment (tx) per product labelling as part of standard of care, with the main objective to explore the time course of response to VDZ as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) domain Short Form (SF) scores. Inclusion criteria include baseline PROMIS Pain Interference (PI)-SF T-score ≥55 (0.5 SD above general population). We enrolled pts via Takeda pt support program in Canada, with additional pts enrolled at US and Canada sites. Planned sample size is 300 pts (VDZ, 200; anti-IL-23 antagonist [reference group not for formal comparison], 100); planned follow-up is 52 weeks (wks), with PROMIS PI data reported weekly for the first 14 wks. The primary endpoint is time to the first meaningful clinical improvement in PROMIS PI-SF T-score, defined as ≥2-point decrease in PROMIS PI-SF T-score from baseline. We also collect data on improvement in 7 PROMIS domains with clinical improvement defined as 5-point (0.5 SD)3 change in T-score from baseline, Short Inflammatory Bowel Disease Questionnaire (SIBDQ; including SIBDQ improvement [≥9 point increase from baseline] and SIBDQ remission [score of ≥60]) and safety. Here, we report the results from pts with ≥1 VDZ dose and ≥1 post-baseline PI assessment included in the interim analysis (IA; prespecified to occur after 50 pts from VDZ group completed or discontinued before the wk 14 assessment to provide an early evaluation of tx response and safety).
Results
Overall, 64 pts with ≥1 VDZ dose and ≥1 post-baseline PROMIS PI assessment (mean±SD age, 43.1±17.0 years, 35.9% male, 92.2% White) were included in the IA. Disease duration (mean±SD) was 6.4±12.1 years; 84.4% of pts were anti-TNF-naïve. Data collection is ongoing for 57 pts (49 with and 8 without completed wk 14 PROMIS PI questionnaire); 7 pts discontinued from the study. The median time to achieve the first ≥2-point decrease in PROMIS PI-SF T-score (in n=56 pts) was 12 days (95% CI, 6-13). Baseline PROMIS domain scores indicated notable impairment; by wk 14, improvements in mean PROMIS scores from baseline were observed in all 7 measured domains, with ≥5-point improvements in 4/7 domains (Table). At wk 14, 37.5% (24/64) and 7.8% (5/64) pts achieved SIBDQ improvement and remission, respectively. One pt had serious adverse events of appendicitis and diverticulitis, and another pt had a fatal event; none of these were related to VDZ tx.
Table. Summary of PROMIS domain T-scores
PROMIS domain T-score, mean±SD
| Baseline (n=64)
| Week 14 (n=49)
| Change from baseline (n=49)
|
Pain Interference
| 61.7±5.2
| 55.0±10.2
| –6.5±10.0
|
Fatigue
| 62.0±6.4
| 53.9±11.5
| –8.4±10.6
|
Anxiety
| 60.2±7.4
| 54.7±10.2
| –5.5±8.6
|
Depression
| 56.4±8.6
| 52.9±10.9
| –3.9±8.6
|
Physical Function
| 42.0±6.2
| 45.3±9.0
| 3.5±7.8
|
Sleep Disturbance
| 56.3±6.9
| 54.5±9.9
| –1.5±7.2
|
Ability to Participate in Social Roles and Activities
| 43.2±6.3
| 49.0±11.2
| 5.9±10.1
|
| T-score of 50±10 reflects the mean±SD score of the general US population.3 Higher T-scores in PROMIS Pain Interference, Fatigue, Anxiety, Depression and Sleep Disturbance domains reflect greater impairment (poorer quality of life); higher T-scores in PROMIS Physical Function and Ability to Participate in Social Roles and Activities domains reflect less impairment (better quality of life).4 |
Conclusion
The IA results through wk 14 show an early improvement across multiple symptom domains and quality of life in pts with CD starting VDZ tx. Time to first ≥2-point decrease in PROMIS PI-SF T-score was short, with a benefit observed after 12 days from VDZ initiation. Study recruitment and data collection are ongoing.
References
1. Keefer L, et al. Gastroenterology. 2022;162(5):1439-1451.
2. Kitchen H, et al. Crohns Colitis 360. 2020;2(2):otaa033
3. Cella D, et al. Value Health. 2019;22(5):537-544.
4. Shaw BE, et al. Cancer. 2018;124(4):841-849.
Disclosure
This study was sponsored by Alimentiv, Inc.
V. Jairath reports consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Tillotts and Fresenius Kabi.
M. Long reports consulting fees from AbbVie, Alimentiv, Bristol Myers Squibb, Intercept, Janssen, Lilly, Pfizer, Prometheus, Roivant, Syneos Health and Takeda; and research support from Lilly, Pfizer and Takeda.
M.D. Kappelman reports being a consultant to Eli Lilly and Takeda.
G. Radulescu and N. Li are employees of Alimentiv.
J.J. Wu, I. Romo Bautista, A. Insogna and C. Agboton are employees of Takeda and hold stock and/or share options in Takeda.
N. Narula has received advisory board/consulting honoraria from Abbvie, Amgen, Eli Lilly and Company, Ferring, Fresinius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda.
