DUAL BIOLOGICAL OR SMALL MOLECULE TREATMENT IN INFLAMMATORY BOWEL DISEASES: DATA FROM CLINICAL PRACTICE

Abstract

Abstract INTRODUCTION Despite significant impact biological treatment had on prospects of patients with IBD, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to therapy. Strategies to avert treatment failure include dose optimization, selection of drugs with different mechanism of action or recently combination of two different targeted molecules in cases where inflammatory activity is not under control. METHODS Patients failing on all available treatment modalities in whom surgery was not possible or was to be avoided and in whom combined treatment with two biological agents or biological agent and a small molecule was started were included. Data on demographics, treatment details, treatment persistence and disease activity including laboratory parameters and clinical activity indices - Harvey-Bradshaw for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC) were collected. Treatment response was evaluated using simple physician’s global assessment (PGA) as no, partial or full response. RESULTS In total, 25 patients were started on dual therapy between September 2020 and May 2021, 68% with CD and 32% with UC. Mean age of the cohort was 34.4±10.9 years, 56% were males and 44% females. Mean disease duration at baseline was 11.2±6.6 years. The follow-up continued until September 2021, median survival on therapy was 45.4 weeks and it was stopped in 40% of patients during the follow-up period. Reasons for termination included poor response, allergic reaction, unsatisfactory pharmacokinetics, advancement to surgery and denial by health insurance company. The included patients were complicated with low age of onset in CD (20.7±8.6 years), dominantly ileocolonic involvement (77%), 35% with proximal disease and 35% with perianal disease. Over 88% underwent abdominal surgery in the past. Two thirds of patients had extensive UC. Various combinations of drugs have been used with prevailing combination of ustekinumab (UST) and vedolizumab (VDZ) (41%) and UST with adalimumab (35%) in CD and VDZ with tofacitinib (63%) in UC. While in CD the overall clinical PGA response was poor with only 30% of patients at least partially responding at week 30, in UC 80% of patients were responders at week 30 (Figures 1 and 2). Apart from two infusion reactions, no other adverse events raising safety concerns occurred during the follow-up. Direct costs of the dual therapy were estimated to be 5-8 times higher as compared to the standard therapy with anti-TNF drug. CONCLUSIONS Dual therapy proved to be feasible option that can be employed without significant safety concerns in a carefully selected group of patients. Patients with colonic involvement seemed to benefit the most from the treatment, however, high incurred costs currently limit more widespread use of dual therapy in common clinical practice.