Tag Archives: Crohn's disease

Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

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A Hart et al. Gastroenterol 2025 (ePUB Ahead of Print) Open Access! Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 GRAVITI Study

Background: “Guselkumab is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 by binding to the p19 subunit and to CD64, a receptor on cells that produce IL-23…In the double-blind Phase 2 GALAXI 1 study and the 2 identically designed double-blind Phase 3 GALAXI 2 and GALAXI 3 studies, guselkumab intravenous (IV) induction (200 mg at weeks 0, 4, and 8) followed by subcutaneous (SC) maintenance (200 mg every 4 weeks or 100 mg every 8 weeks) demonstrated efficacy compared with placebo… In addition, guselkumab demonstrated superiority to ustekinumab for multiple endoscopic-based endpoints at week 48 in pooled data from GALAXI 2 and GALAXI 3… The GRAVITI study…evaluated the efficacy and safety of guselkumab SC induction followed by SC maintenance in participants with moderately to severely active Crohn’s disease.

Methods: This was a Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400 mg SC every 4 weeks→100 mg SC every 8 weeks (n = 115), guselkumab 400 mg SC every 4 weeks→200 mg SC every 4 weeks (n = 115), or placebo (n = 117).  Placebo participants meeting rescue criteria received guselkumab from week 16 onward. 

Key Findings:

  •  At week 12, significantly greater proportions of participants receiving guselkumab 400 mg achieved clinical remission vs placebo (56.1% vs 21.4%; P < .001), and endoscopic response vs placebo (41.3% vs 21.4%; P < .001)
  • At week 48, significantly greater proportions of participants in both guselkumab groups (100 mg SC every 8 weeks: 60.0%; 200 mg SC every 4 weeks: 66.1%) achieved clinical remission vs placebo (17.1%; P < .001 each) and endoscopic response (44.3%; 51.3%; vs placebo 6.8%; P < .001 each)
  • Immunogenicity: “Antibodies to guselkumab were detected in 24 (8.8%) of the 274 guselkumab-treated participants through week 48. Only 3 of 274 participants (1.1% of the total population) were positive for neutralizing antibodies. Through week 48, no impact of antibodies to guselkumab on serum guselkumab concentrations, efficacy, or injection-site reactions was observed”
At week 12: Compared to placebo, patients receiving Guselkumab had improved clinical remission and endoscopic response. Being naive to previous biologics was associated with a higher endoscopic response but with a lower clinical remission rate.
At week 48: Being naive to previous biologics was associated with a higher clinical remission
At week 48: Being naive to previous biologics was associated with a higher endoscopic remission

Discussion: “The results presented here from GRAVITI were consistent with those reported in the double-blind, treat-through GALAXI trials in which guselkumab induction was administered IV in participants with moderately to severely active Crohn’s disease. For example, 41.3% of participants in the GRAVITI study achieved endoscopic response 12 weeks … whereas 36.9% of participants in the pooled GALAXI studies achieved endoscopic response 12 weeks after guselkumab… IV induction (placebo: 12.2%).”

My take: This study shows that Guselkumab with a SC induction is safe and effective in participants with moderately to severely active Crohn’s disease. IV induction does not appear to be needed. Though IL-23 agents have been important advances, there are still a large number of patients without a good response.

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New FDA Rinvoq (upadacitinib) Indication: Oral Treatment For Crohn’s

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5/18/23: FDA approves first oral treatment for moderately to severely active Crohn’s disease

“Patients should start with 45 mg of Rinvoq once daily for 12 weeks. Following the 12-week period, the recommended maintenance dosage is 15 mg once a day. A maintenance dosage of 30 mg once daily can be considered for patients with refractory, severe, or extensive Crohn’s disease.”

“The most common side effects of Rinvoq as indicated for Crohn’s disease are upper respiratory tract infections, anemia, fever, acne, herpes zoster, and headache…. Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis have occurred with JAK inhibitors such as Rinvoq.”

Tucson Botanical Gardens

IBD Update: MMR Vaccine and Lower Rates of IBD, Humira Biosimilar Data, Oral Health Associated with IBD Activity, Low Chance of Reconnection After Fecal Diversion

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C Kim et al. Inflamm Bowel Dis 2023; 29: 430-436. Vaccination Against Measles, Mumps, Rubella and Incident Inflammatory Bowel Disease in a National Cohort of Privately Insured Children

This retrospective cohort study (n = 1 365 447) using de-identified claims data from a national private payer (Optum Clinformatics Data Mart), between 2001 and 2018 found that receipt of at least 1 dose of MMR had lower risk for IBD than children who did not (hazard ratio, 0.71; 95% confidence interval, 0.59-0.85). This association persisted after adjustment for potential confounding factors.

My take: This study provides reassurance to encourage MMR vaccination

A Tursi et al. Inflamm Bowel Dis 2023; 29: 376-383. Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study

In this retrospective study (n=533), compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. Key findings:

  • Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics
  • Clinical remission was maintained in 81.0% of patients switched from the originator
  • No difference in efficacy and safety was found between ADA biosimilars.

My take: This study suggests that these biosimilars are equally effective; however, the fact that nearly 20% failed to maintain remission after switching from the originator ADA indicates more comparative (prospective) studies are needed

Related blog post: Adalimumab Biosimilars on the Horizon (Finally) Plus Two Studies

GR Madsen et al. Inflamm Bowel Dis 2023; 29: 396-404. The Impact of Periodontitis on Inflammatory Bowel Disease Activity

Key finding: In this questionnaire-based study among 1093 patients with inflammatory bowel disease (IBD), periodontitis and tooth loss were significantly associated with increased IBD-related disability and more disease activity in the preceding 12 month. This type of study does not allow one to draw conclusions about causality but does provide a good rationale to encourage regular attention to oral health/dentistry.

G Kassim et al. Inflamm Bowel Dis 2023; 29: 417-422. Long-Term Outcomes of the Excluded Rectum in Crohn’s Disease: A Multicenter International Study

Methods: In this retrospective study (n=197) reviewed all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up.

Key findings:

  • 92 (47%) of 197 patients ultimately underwent subsequent proctectomy; only 20 (10%) remained symptom-free with excluded rectums.
  • Only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems

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“Temporary” Diversion for Distal Crohn’s Disease & Latest COVID Stats

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AL Lightner et al. Inflamm Bowel Dis 2022; 28: https://doi.org/10.1093/ibd/izab126. Is Intestinal Diversion an Effective Treatment for Distal Crohn’s Disease?

In this retrospective study (n=132 adults), the indications for surgery were medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%)

Key findings :

  • The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16).
  • At a median follow-up of 35.3 months, 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms
  • Also, 24% experienced stoma morbidity (peristomal abscess, hernia or prolapse)

My take: In this study of adults with distal Crohn’s disease, a “temporary” stoma/fecal diversion was only temporary in ~20%. This information is quite important for patients when considering this treatment option.

Associated commentary: NEK Wieghard. Inflamm Bowel Dis 2022; 28: 325-326. The Difficulty of Distal Crohn’s Disease and the Utility of Diverting Stomas

From March 8, 2022