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Review
. 2022 Dec 21;28(47):6743-6751.
doi: 10.3748/wjg.v28.i47.6743.

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Domingo Balderramo  1
Affiliations
Review

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Domingo Balderramo. World J Gastroenterol. .

Abstract

Inflammatory bowel disease (IBD) is a group of chronic diseases that includes ulcerative colitis, Crohn's disease, and indeterminate colitis. Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management. The treatment of patients with IBD is focused on achieving therapeutic goals including clinical, biochemical, and endoscopic variables that result in improvement of the quality of life and prevention of disability. Advanced IBD treatment includes tumor necrosis factor inhibitors, integrin antagonist, antagonist of the p40 subunit of interleukin 12/23, and small molecule drugs. However, despite the multiple treatments available, about 40% of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life, with hospitalization and surgery being necessary in many cases. Dual therapy, a strategy sometimes applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD patients in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases. This review provides a summary of the results (clinical response and remission) of different combinations of advanced drugs in patients with IBD, both in adults and in the pediatric population. In addition, the safety profile of different combinations of dual therapy is analyzed. The use of newer combinations, including recently approved treatments, the application of new biomarkers and artificial intelligence, and clinical trials to establish effectiveness during long-term follow-up, are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.

Keywords: Clinical remission; Crohn’s disease; Dual-therapy biologic therapy; Inflammatory bowel disease; Small molecule drugs; Ulcerative colitis.

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Conflict of interest statement

Conflict-of-interest statement: Balderramo D reports receiving payment for speaker´s fee from AbbVie, Takeda, and Janssen, and receiving consulting fees from AbbVie, Takeda, Janssen, and Amgen.

Figures

Figure 1
Figure 1
Number of therapeutic trials described in studies including 2 or more inflammatory bowel disease patients. TNFi: Tumor necrosis factor inhibitor; TOF: Tofacitinib; UST: Ustekinumab; VDZ: Vedolizumab.
See this image and copyright information in PMC

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