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

Phase 4RecruitingNCT07616687

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives210 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * \- 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. Exclusion Criteria: * \- 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

Outcomes

Primary Outcomes

- Steroid free clinical remission (SFCR) associated with fecal calprotectin < 250 ug/g at Week 48

Steroid-free clinical remission (SFCR), defined as clinical remission measured by the patient reprt outcome, PRO2 : abdominal pain ≤ 1 and stool frequency ≤ 3, without corticosteroid use at the time of assessment, combined with fecal calprotectin \< 250 µg/g.

Time frame: 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

Steroid free clinical remission measured by abdominal pain ≤ 1 and stool frequency ≤ 3 with feacal calprotection \< 250 ug/g at Week 48

Time frame: Week 48 (+/-12Weeks)

Secondary Outcomes

- 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),

Evaluation of the morphological remission at W48 by one of the morphological exams: endoscopy: SES-CD \<3 points, MRI: bowel wall thickness ≤3 mm without contrast enhancement, IUS: bowel wall thickness ≤3 mm without color doppler signal

Time frame: Week 48

SFCR associated with fecal calprotectin < 250 ug/g at Week 12, Week 24 and Week 48,

Evaluation of the clinical remission by PRO2: abdominal pain ≤ 1 and stool frequency ≤ 3, without corticoids associates with a biological remission defined by calprotectin \< 250 ug/g