Optimal Care With Guselkumab in Crohn's Disease / OPTIM Study A Prospective Open Label Interventional, Multicenter Study

Официальное название

Optimal Care With Guselkumab In Crohn's Disease

Обзор

Crohn's disease (CD) is a chronic and destructive inflammatory disease of the gastrointestinal tract characterized by phases of relapse and remission. Tumor necrosis factor (TNF) antagonists, anti-integrins and anti-interleukin (IL) 12/23 are the main therapeutic agents to obtain deep remission and prevent disability. Despite the significant advances these biologics represent in treating inflammatory bowel disease (IBD), many patients experience suboptimal responses, including primary non-response or a loss of effectiveness over time, often leading to treatment discontinuation. For all these medications, a dose-response relationship has been demonstrated and an increase in dose or dosing frequency is recommended. Dose escalation is now an essential therapeutic approach necessary in 30 to 50% of CD patients treated with biologics. This strategy, supported by international guidelines, allows for long-term efficacy to be maintained without compromising safety. Guselkumab (GUS) is a monoclonal antibody targeting the p19 subunit of IL-23. In a recent phase III trial (GALAXI), GUS demonstrated superiority of both subcutaneous (SC) maintenance doses (200 mg every 4 weeks \[q4w\] and 100 mg every 8 weeks \[q8w\]) compared to placebo and ustekinumab. In the GALAXI phase III program, at least 30% of patients did not achieve clinical response after a 12-week intravenous induction, and almost 20% experienced a loss of response by week 44. In these patients, the benefit of an intensified dose of GUS (200 mg q4w) maintenance remains to be determined to guide clinicians in optimizing its use in clinical practice. The investigator aimed to evaluate the one-year effectiveness of GUS in CD in real-world settings and under optimal conditions allowing dose intensification.

Подробное описание

Interventionnel, open multicenter study, the objectives are:

Primary Objective To evaluate the one-year effectiveness of GUS in CD in real-world setting.

Secondary Objectives

* To evaluate the effectiveness of GUS intensification from 100 mg q8w to 200 mg q4w in patients with loss of response, * To evaluate the effectiveness of an intensified GUS 200 mg q4w maintenance therapy in patients who are primary non-responders to GUS SC induction at 12 weeks; * To assess the factors associated with GUS intensification effectiveness.

Вмешательства

• Препарат Guselkumab
  Guselkumab is a human monoclonal antibody targeting IL-23. In this study, patients receive guselkumab as part of a treat-to-target strategy. At week 12 (W12), patients are managed according to disease response: those with adequate response continue standard maintenance dosing, while non-responders are escalated to an intensified treatment regimen with adjusted dosing frequency.

Первичные конечные точки

• - Steroid free clinical remission (SFCR) associated with fecal calprotectin < 250 ug/g at Week 48 [Срок оценки: Week 48 +/- 12Weeks for the patients who are intensified between Week 32 and Week 48]
• - Steroid free clinical remission (SFCR) associated with fecal calprotectin < 250 ug/g at Week 48 [Срок оценки: Week 48 (+/-12Weeks)]

Вторичные конечные точки (10)

• - Morphological remission at Week 48 assessed using the same tool that was used for the patient's inclusion: endoscopy, MRI or IUS (major secondary endpoint), [Срок оценки: Week 48]
• SFCR associated with fecal calprotectin < 250 ug/g at Week 12, Week 24 and Week 48, [Срок оценки: Week 12, Week 24 and Week 48]
• Clinical remission at Week 12, Week 24 and Week 48 [Срок оценки: Week 12, Week 24 and Week 48]
• Biomarker remission at Week 12, Week 24 and Week 48 [Срок оценки: Week 12, Week 24 and Week 48,]
• Need for GUS dose intensification (Week 12, Week 24 and Week 48) [Срок оценки: Week 12, Week 24 and Week 48]
• Serum levels of guselkumab (Week 12, Week 24 and Week 48) [Срок оценки: Week 12, Week 24 and Week 48]
• Neutralizing antibodies to guselkumab (Week 12, Week 24 and Week 48) [Срок оценки: Week 12, Week 24 and Week 48]
• Crohn's Disease-related hospitalization during study period (Week 12, Week 24 and Week 48) [Срок оценки: Week 12, Week 24 and Week 48]
• -Change in the Short Inflammatory Bowel Disease Questionnaire(SIBD-Q) from baseline (Week 12, Week 24 and Week 48) [Срок оценки: Week 12, Week 24 and Week 48]
• Guselkumab persistence [Срок оценки: Week 48]

Критерии участия

Критерии включения

• \- Patients with a diagnosis of CD according to ECCO guidelines,
• 18 years of age or older at the time of informed consent,
• Absence of contraindication to guselkumab,
• Active disease according to PRO2 (abdominal pain > 1 or stool frequency > 3), and faecal calprotectin > 250 ug/g,
• Objective active disease documented within ≤ 2 months by endoscopy or by MRI when not contraindicated, orby IUS),
• Not currently participating in any interventional research.
• Patient naïve or exposed to one or more advanced therapy, in accordance with the approved indication for guselkumab in Crohn's disease.
• Females of childbearing potential must have a negative serum pregnancy test at the baseline Visit.

Критерии исключения

• \- Patient under legal protection,
• Previous exposure to an anti-IL23
• Combination of advanced therapy with GUS,
• Patient with ostomy,
• Pregnant or breastfeeding woman,
• Patient with perianal CD predominant disease.
• Active clinically significant infection or HIV, Hep B, Hep C, or active tuberculosis

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Chu Amiens Picardie — Amiens

Публикации

• Dolinger M, Torres J, Vermeire S. Crohn's disease. Lancet. 2024 Mar 23;403(10432):1177-1191. doi: 10.1016/S0140-6736(23)02586-2. Epub 2024 Mar 1. PMID 38437854
• 7. Panaccione R, Hart A, Steinwurz F et al. S1052 Efficacy and Safety of Subcutaneous Guselkumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease: Results Through Week 48 From the Phase 3 GRAVITI Study. Am J Gastroenterology 119(10S):p S740-S741, October 2024
• 6. Panaccione, R et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn's disease: results of the GALAXI 2 & 3 phase 3 studies. Oral presentation (Abstract #1057b) at Digestive Disease Week (DDW) 2024. May 2024.
• Gordon H, Minozzi S, Kopylov U, Verstockt B, Chaparro M, Buskens C, Warusavitarne J, Agrawal M, Allocca M, Atreya R, Battat R, Bettenworth D, Bislenghi G, Brown SR, Burisch J, Casanova MJ, Czuber-Dochan W, de Groof J, El-Hussuna A, Ellul P, Fidalgo C, Fiorino G, Gisbert JP, Sabino JG, Hanzel J, Holubar S, Iacucci M, Iqbal N, Kapizioni C, Karmiris K, Kobayashi T, Kotze PG, Luglio G, Maaser C, Moran PMID 38877997
• Peyrin-Biroulet L, Danese S, Argollo M, Pouillon L, Peppas S, Gonzalez-Lorenzo M, Lytras T, Bonovas S. Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2019 Apr;17(5):838-846.e2. doi: 10.1016/j.cgh.2018.06.026. Epub 2018 Jun 20. PMID 29935327
• Singh S, Murad MH, Fumery M, Sedano R, Jairath V, Panaccione R, Sandborn WJ, Ma C. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1002-1014. doi: 10.1016/S2468-1253(21)00312-5. Epub 2021 Oct 22. PMID 34688373
• Feuerstein JD, Ho EY, Shmidt E, Singh H, Falck-Ytter Y, Sultan S, Terdiman JP; American Gastroenterological Association Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology. 2021 Jun;160(7):2496-2508. doi: 10.1053/j.gastro.2021.04.022. No abstract available. PMID 34051983

Идентификаторы

NCT: NCT07616687 · GETAID-2025-03 · 2025-524573-16-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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