Biologic monotherapy versus combination therapy with immunomodulators in the induction and maintenance of remission of Crohn’s disease and ulcerative colitis

Abstract

Despite current guidelines, the optimal treatment of patients with inflammatory bowel disease (IBD) remains challenging. The available medications are not without risk and there is not a single correct treatment regimen for every patient. Personalizing treatment and selecting the most appropriate therapy is crucial for optimal response, remission, quality of life, and healthcare utilization. Biologics, especially anti-tumor necrosis factor-α medications, are widely used in the induction and maintenance of disease remission in patients with IBD. Similarly, immunomodulators, including thiopurines and methotrexate, are traditionally popular for the maintenance of remission. In this manuscript, we review the use of biologic monotherapy vs. combination therapy with immunomodulators for the treatment of ulcerative colitis and Crohn’s disease. We examine overall remission, immunogenicity and adverse effects, mainly serious infections and malignancy, in an effort to help guide treatment decisions and weigh the risks and benefits of biologic monotherapy vs. combination therapy.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

“…Observational studies have demonstrated similar results 64–66. Given that evidence suggests that not all anti-TNF drugs are identical, sharing the same action mechanism and pharmacokinetic properties,57 67 68 in cases where a second anti-TNF is considered, the experts recommend associating an IMM with proactive TDM on induction and maintenance 69 70…”

Risk factors for malignancy and serious infection in patients with inflammatory bowel disease: a retrospective analysis

“…Combination treatments (with an anti-TNF agent and an immunomodulator) in IBD are commonly used to increase treatment effectiveness through synergy of effect and to prevent the formation of anti-drug antibodies. 39 When compared to monotherapy with either an immunomodulator or an anti-TNF, combination therapy does not appear to increase the risk of overall malignancy. 26 This is consistent with the findings of the present analysis, where patients exposed to combination therapies, relative to monotherapy with either a thiopurine or anti-TNF, did not develop malignancy at a higher rate (OR = 0.62; 95% CI = 0.40-1.02).…”

“…Combination treatments (with an anti‐TNF agent and an immunomodulator) in IBD are commonly used to increase treatment effectiveness through synergy of effect and to prevent the formation of anti‐drug antibodies 39 . When compared to monotherapy with either an immunomodulator or an anti‐TNF, combination therapy does not appear to increase the risk of overall malignancy 26 .…”

Azatioprin u liječenju bolesnika s ulceroznim kolitisom

“…21 Veliki je broj dokaza koji podupiru istodobnu primjenu infliksimaba i tiopurina, ponajprije u smislu smanjenja imunogeničnosti, odnosno proizvodnje cirkulirajućih protutijela na spomenutog TNF-α antagonista. 22 Pri opetovanu izlaganju infliksimabu, azatioprin inducira RAC1-om posredovanu T-staničnu apoptozu, te postupno briše memoriju T-staničnih klonova. Na taj način postupno se uklanja od prije stvoreni, memorirani odgovor na antigene infliksimaba.…”