DAY 1: The Potential of Advanced Combination Therapy to Improve Inflammatory Bowel Disease

In a bonus session, Bruce E. Sands, MD, MD, FACG, from Icahn School of Medicine at Mount Sinai, presented on the role of combination therapy in IBD. He noted that the field has reached a therapeutic ceiling with monotherapy (Raine & Danese, 2022), achieving at most 50% clinical and endoscopic remission rates. Combination therapy, along with earlier diagnosis and better monitoring, can help improve individual patient outcomes. Studies have shown mechanistic failure of monotherapy and less effective use of sequential therapies, and that targeting multiple pathologic pathways may be a rational approach to achieving an additive or synergistic effect. Patient selection is an important aspect of reducing the risks and maximizing the benefit of combination therapy. Candidates for advanced combination therapy include very high-risk patients who are refractory to multiple therapies and for whom surgery is not a good option, and who may have extraintestinal manifestations (EIM) associated with immune-mediated inflammatory diseases (IMID). Induction strategies might involve add-on, simultaneous co-induction, or sequential induction approaches. In the maintenance phase, the induction combination might continue as-is, one drug might be withdrawn, or in patients with induction monotherapy, combination therapy can be introduced as needed during maintenance. Systematic reviews and meta-analyses have tried to determine which combinations are preferred, but the data is largely retrospective. A few prospective studies have shown improvement with combination therapy over monotherapy without a significant safety signal (e.g., Colombel et al, 2024, Feagan et al, 2023). There are five classes of drugs that can be combined in numerous ways; in silico analysis could be helpful in identifying effective combinations based on mechanisms of action; this may be particularly useful for individuals with co-existing immune conditions. Some studies have also suggested that early combination therapy can help reduce the risk of immunologic resistance. New avenues of drug development are expected to further expand the options for advanced combination therapy, including oral formulations, bispecific antibodies, and new mechanisms of action.
 

Posters of interest:
Jacob K. Jamison, BA, from Weill Cornell Medicine, described the results of a single-center retrospective analysis of the safety of combination treatment for IBD with two biologic or small molecular therapies for at least 6 weeks. Therapies included anti-TNFs, anti-integrin agents, IL-12 and IL-12/23 inhibitors, JAK inhibitors, and S1P receptor modulators. They assessed hospitalizations, infections, surgeries, and other adverse events during treatment and up to 12 weeks after discontinuation. A total of 102 patients (63% Crohn’s disease [CD] and 37% ulcerative colitis [UC]) received 125 combination regimens, 92% had received steroids previously, 88% had prior treatment with TNF antagonists, and 56% of patients with CD had prior surgery. 65 regimens were discontinued; of these, 13 were discontinued due to adverse events. The most common adverse events were infections (30% of regimens) and dermatologic (15% of regimens). 13% of the regimens involved IBD-related hospitalization and 11% involved IBD surgery. Baseline steroid treatment was associated with a higher rate of serious infection and IBD related hospitalization, and a higher rate of discontinuation due to adverse events. (P1100)

Wafa Alkarni, MBBS, from King Faisal Specialist Hospital, described results from a single center retrospective study of patients with refractory IBD who received upadacitinib in combination with biologic therapy. The study included 10 patients with endoscopically active CD and 4 patients with UC, with a mean disease duration of 7 years. At baseline, 62% of patients had elevated CRP and 93% had elevated fecal calprotectin (FCP). Patients received a combination of upadacitinib and ustekinumab (n=8), vedolizumab (n=4), or risankizumab (n=2). At 4 months, 5 patients had achieved clinical remission and 6 showed clinical response. For 8 patients with endoscopic data, 2 achieved endoscopic remission and 2 showed endoscopic response. Two patients developed a non-serious infection and 1 patient with UC underwent colectomy. (P5382)