Combination treatment of inflammatory bowel disease: Present status and future perspectives

Abstract

The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical gastroenterologist. It seems to be no exaggeration to say that in these patients, not only the scientific background of the gastroenterologist is tested, but also the abundance of “gifts” that he should possess (insight, intuition, determination, ability to take initiative, etc.) for the successful outcome of the treatment. In daily clinical practice, depending on the severity of the attack, IBD is treated with one or a combination of two or more pharmaceutical agents. These combinations include not only the first-line drugs (e.g., mesalazine, corticosteroids, antibiotics, etc) but also second- and third-line drugs (immunosuppressants and biologic agents). It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied. Therefore, a part of these patients are going to surgery. In recent years, several small-size clinical studies, reviews, and case reports have been published combining not only biological agents with other drugs (e.g., immunosuppressants or corticosteroids) but also the combination of two biological agents simultaneously, especially in severe cases. In our opinion, it is at least a strange (and largely unexplained) fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few. As mentioned above, there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations. The appropriate dosage, the duration of the administration, the suitable timing for checking the clinical and laboratory outcome, as well as the treatment side-effects, should be the subject of intense clinical research shortly. In this editorial, we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients. We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Keywords: Biologics for immune-mediated conditions, Dual-targeted treatment, Combination treatment, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis

Core Tip: During the last few years, the combination of two biological agents or a combination of a biological agent and another drug belonging to the category of so-called "small molecules" seems to be steadily gaining ground [dual biologic therapy (DBT)]. Even the combination of a biological agent with a drug belonging for example to the category of immunosuppressants is a therapeutic option that has been applied for several years [combination therapy (CT)]. Finally, in daily clinical practice, various combinations of so-called first-line drugs (mesalazine, corticosteroids, antibiotics, probiotics, etc.) are used with satisfactory results in most cases. DBT and CT currently find application in cases of patients resistant to treatment or patients with extraintestinal manifestations that do not respond satisfactorily to classical treatment. The existing data, although encouraging, are not sufficient in terms of the number of patients included so far. The safety of this emerging kind of treatment is another point of interest. Finally, there is a need to carry out more studies regarding this interesting field of research.