Key Advances in Inflammatory Bowel Disease: New Therapies, Treatment Strategies, and Long-Term Data
Key Insights
Early, intensive 'top-down' therapy with TNF (search) blockers plus immunomodulators shows superior outcomes compared to the traditional 'step-up' approach for newly diagnosed Crohn's disease (search).
Risankizumab (Skyrizi) and guselkumab (Tremfya) receive FDA approval for ulcerative colitis (search), offering new options for patients who have not responded well to conventional treatments.
Research indicates intensified infliximab dosing does not improve outcomes in steroid-refractory acute severe ulcerative colitis (search), suggesting a need for alternative strategies.
The landscape of inflammatory bowel disease (IBD (search)) treatment saw significant developments in 2024, with new therapeutic options, refined treatment strategies, and extended data on promising investigational drugs. These advances offer hope for improved outcomes and quality of life for patients with Crohn's disease (search) and ulcerative colitis (search).
Top-Down Therapy for Crohn's Disease
In a notable shift in treatment paradigm, the PROFILE trial demonstrated that early and intensive "top-down" therapy is more effective than the conventional "step-up" approach for newly diagnosed Crohn's disease (search). The study, published in Lancet Gastroenterology & Hepatology, randomized 386 patients and found that sustained steroid- and surgery-free remission at 48 weeks was significantly higher in the top-down group (TNF (search) blockers plus an immunomodulator) compared to the step-up group (79% vs 15%, P <0.0001).
"The case appears clear-cut for implementation of top-down treatment as the standard of care for most patients as soon as possible after diagnosis," concluded Nurulamin Noor, PhD, of the Cambridge University Hospitals NHS Foundation Trust.
Notably, the top-down approach also resulted in fewer adverse events (168 vs 315), fewer serious adverse events (15 vs 42), and fewer complications requiring surgery (one vs 10).
New Approvals for Ulcerative Colitis
The FDA approved two new therapies for moderately to severely active ulcerative colitis (search): risankizumab (Skyrizi) and guselkumab (Tremfya). Risankizumab, an interleukin (IL)-23 inhibitor, was approved based on the INSPIRE and COMMAND trials. The 12-week INSPIRE trial showed a significantly improved clinical remission rate with risankizumab compared to placebo (24% vs 8%). The 52-week COMMAND maintenance study demonstrated clinical remission rates of 41-45% with risankizumab compared to 26% with placebo.
Guselkumab's approval was based on findings from the QUASAR phase IIb/III induction and maintenance program. The studies showed significantly higher rates of clinical remission at 44 weeks (45-50% vs 19% with placebo) and higher rates of endoscopic remission at 1 year of maintenance (34-35% vs 15%) with guselkumab.
Intensified Infliximab Dosing Questioned
The PREDICT-UC trial challenged the practice of intensified infliximab dosing in patients with steroid-refractory acute severe ulcerative colitis (search) undergoing rescue therapy. The study found no significant difference in clinical response by day 7 between patients receiving a first dose of 10 mg/kg and those receiving 5 mg/kg (65% vs 61%; risk ratio adjusted for thiopurine treatment history 1.06, 95% CI 0.94-1.20, P =0.32).
Furthermore, there were no significant differences in longer-term endpoints, including clinical remission, steroid-free remission, endoscopic remission, or rates of colectomy at 3 months.
"The PREDICT-UC study potentially signals the end of accelerated or intensified dosing strategies for infliximab as rescue therapy for acute severe ulcerative colitis (search), which should prompt new strategic approaches," noted Saurabh Kedia, MD, and Vineet Ahuja, MD, of the All India Institute of Medical Sciences in an editorial accompanying the study.
Long-Term Data on Tulisokibart
Extended data from the phase II ARTEMIS-UC and APOLLO-CD trials showed that the investigational monoclonal antibody tulisokibart maintained clinical and endoscopic improvements at nearly 1 year in patients with IBD (search). In the ARTEMIS-UC trial, 48% of patients with ulcerative colitis (search) who received 250 mg of intravenous tulisokibart were in clinical remission at 50 weeks. In the APOLLO-CD trial, 56% of patients with Crohn's disease (search) who received 250 mg of tulisokibart achieved clinical remission at week 50. Tulisokibart is set to advance to phase III trials for ulcerative colitis and Crohn's disease.