One-Year Real-World Effectiveness of Subcutaneous Guselkumab in Adults with Crohn’s Disease

The primary objective is to evaluate the one‑year effectiveness of guselkumab in patients with Crohn's disease in a real‑world setting, providing clinically relevant data on long‑term disease control and informing therapeutic decision‑making. Secondary objectives are to:

• Assess the effectiveness of guselkumab dose intensification from 100 mg every 8 weeks to 200 mg every 4 weeks in patients who experience loss of response.
• Determine the effectiveness of an intensified 200 mg every 4 weeks maintenance regimen in patients who are primary non‑responders to the subcutaneous induction course at week 12.
• Identify factors associated with the success of guselkumab intensification.

The trial intended to enroll adult individuals diagnosed with Crohn's disease according to ECCO guidelines. Both female and male participants were eligible, with eligibility beginning at 18 years of age. Enrollment required evidence of active disease, defined by a PRO2 score indicating abdominal pain > 1 or stool frequency > 3, fecal calprotectin > 250 µg/g, and corroborating objective findings on endoscopy, MRI, or intestinal ultrasound within the preceding two months. Additional requirements included the absence of contraindications to guselkumab, no concurrent participation in other interventional research, and a history of either being naïve to or previously exposed to advanced therapies. The sponsor did not provide information on the total number of participants or specific age distribution beyond the adult inclusion criterion.

The study is a phase IV, single‑arm, real‑world effectiveness trial evaluating the one‑year efficacy of subcutaneous guselkumab 400 mg in adults with Crohn's disease. After an initial screening visit confirming diagnosis, active disease (PRO2 criteria, fecal calprotectin > 250 µg/g, and objective endoscopic/MRI/IUS evidence within 2 months) and eligibility, participants receive the first dose at the baseline visit. Subsequent study visits are scheduled at weeks 12, 24 and 48, during which clinical status, steroid use, fecal calprotectin, imaging‑based remission, quality‑of‑life (Short IBD‑Q) and need for dose intensification are assessed. The week‑48 visit constitutes the end‑of‑study assessment. Participant involvement spans approximately 48 weeks from baseline to the final evaluation, with the overall trial recruitment period defined from 30 April 2026 to 1 October 2028. Early discontinuation may occur if a participant withdraws consent or is unable to continue per protocol requirements.

The investigational product is guselkumab, supplied as a solution for injection in a pre‑filled syringe containing 100 mg/mL. Each administered dose consists of 400 mg given by subcutaneous injection. The pharmaceutical form is designated as an injection/infusion solution, and the product name appears on the labeling as “Guselkumab – solution for injection in pre‑filled syringe – 100 mg/mL.”

No additional non‑experimental treatments, such as placebo or standard‑of‑care therapy, are listed for this study; the protocol specifies the use of the investigational medication alone.

Administration of the study drug follows the dosing schedule defined in the protocol, with each 400‑mg dose delivered subcutaneously according to the prescribed interval. Participant compliance with dosing is monitored through site‑based documentation of each injection, verification of remaining volume in the pre‑filled syringes, and recording of any deviations from the scheduled regimen.

Efficacy will be evaluated in participants with Crohn's disease using both a primary and multiple secondary endpoints. The primary efficacy endpoint is steroid‑free clinical remission (SFCR) together with a fecal calprotectin concentration below 250 µg/g assessed at week 48.

Secondary efficacy assessments include:

• Morphological remission at week 48 determined by the same imaging modality used at screening (endoscopy, magnetic resonance imaging, or intestinal ultrasound).
• SFCR with fecal calprotectin < 250 µg/g at weeks 12, 24, and 48.
• Clinical remission at weeks 12, 24, and 48.
• Clinical response at week 12.
• Biomarker remission at weeks 12, 24, and 48.
• Requirement for guselkumab dose intensification at weeks 12, 24, and 48.
• Change from baseline in the Short IBD‑Q quality‑of‑life index at weeks 12, 24, and 48.

Assessments will be performed using validated clinical scoring systems, quantitative fecal calprotectin assays, and standardized imaging protocols. The Short IBD‑Q questionnaire will be administered to capture patient‑reported outcomes. Data will be collected at baseline and at the specified timepoints (weeks 12, 24, and 48) and analyzed according to the predefined statistical analysis plan.