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BACKGROUND Therapies for ulcerative colitis include mesalamine, immunomodulators, biologics, and small molecules. Unfortunately, patient response is not universal, and efficacy can diminish with time, postulated to be from increased drug clearance, anti-drug antibodies with biologics, and immune mediated pathogenesis changes. Biologic combinations have been investigated for producing synergistic drug effects and extending targeted therapy in patients lacking monotherapy response, with promise shown in two drug combinations (1), but not investigated using three. CASE A 20-year-old Caucasian male with UC presented in August 2015 following 1 month hospitalization for Clostridium difficile infection. He had 2 infusions of infliximab 10 mg/kg continued post-discharge, and started mesalamine 4.8gm qd, 6-mercaptopurpine (6MP) 100mg qd, and prednisone taper. By November 2015, colonoscopy showed severe Mayo 3 pancolitis. Due to insufficient response 6MP and infliximab were discontinued and he started vedolizumab. August 2016 colonoscopy had chronic colitis with Mayo 2 inflammation of the ascending, transverse, descending and rectosigmoid colon so prednisone 40mg was initiated and vedolizumab increased to vedolizumab q4 weeks. He responded well clinically and was tapered off prednisone by October 2016. November 2016 colonoscopy had right sided colitis resolution with residual proctosigmoiditis (Mayo 2); May 2017 colonoscopy still had rectosigmoid inflammation (Mayo 2) with chronic active colitis, so ustekinumab q8 weeks was added. December 2017 colonoscopy was unimproved so ustekinumab increased to q4 weeks, prednisone was increased, and he requested addition of budesonide and mesalamine. With clinical improvement, prednisone was tapered by February 2020. However, December 2020 colonoscopy showed severe (Mayo 3) recto-sigmoiditis with mild colitis in the descending to transverse colon, so tofacitinib XR 22 mg qd was added. He improved clinically, so budesonide was discontinued in February 2021. November 2021 colonoscopy showed complete endoscopic remission (Mayo 0) so he initiated de-escalation with initially discontinuing mesalamine and increasing ustekinumab initially to q8 week intervals and later vedolizumab to q8 weeks with maintenance of clinical remission. Given marginal effect, ustekinumab was discontinued initially and later, tofacitinib was discontinued. He remains in remission on vedolizumab q8 weeks monotherapy. CONCLUSION Combination therapies may be considered for suitable patients experiencing severe, refractory disease. Although patients with multiple comorbidities, frailty, immunosuppression or certain contraindications may not be well suited, this patient presents as an ideal candidate with no comorbidities and few other therapeutic options. REFERENCES (1) Privitera G et al. Combination therapy in IBD. Autoimmunity Reviews. 2021 Jun 1;20(6):102832.

Background:The endoscopic Mayo score (MS) is the most frequent score used for the evaluation of inflammatory activity in Ulcerative Colitis (UC), varying from 0 to 3 points. Recently the DUBLIN score (DS) emerged, which varies from 0 to 9 points and results from the product of the MS and the disease extent, according to Montreal classification, E1-E3. In this study we aimed to evaluate and compare the predictive ability of MS and DS for long term treatment failure. Methods: A retrospective and unicentric study was conducted, including patients with left-sided or extensive UC, asymptomatic and without the need for steroid therapy or therapy changes in the 6 months prior to undergoing total colonoscopy with calculation of MS and DS. Treatment failure was evaluated, defined by the need for therapy changes and/or hospitalization because of disease exacerbation, over a follow-up period of a minimum of 24 months and a maximum of 84 months. Results: A total of 204 patients were included, 104 (51%) females and with a mean age at diagnosis of 36.4 6 12.7 years. In the initial evaluation, 48 (23.5%) were being treated with anti-TNFa medication. The mean values of MS were 1.0 6 1.1 points and of DS were 2.2 6 2.6 points. During follow-up, 32 (15.7%) patients experienced treatment failure and patients initially treated with anti-TNFa medication had 2.3 times higher risk of treatment failure (P 5 0.042). MS values (AUC 0.809; P , 0.001; with sensitivity of 0.938 and specificity of 0.529 for values equal or superior to 1) and DS values (AUC 0.789; P , 0.001; with sensitivity of 0.844 and specificity of 0.581 for values equal or superior to 2) had good discriminative abilities in predicting treatment failure. There were no statistically significant differences in the discriminative ability between both scores (P 5 0.340). Conclusion(s): MS and DS had good discriminative abilities in predicting treatment failure. However, the integration of the disease extent in the DS as a complement of MS in the evaluation of UC was not associated with a higher predictive ability of long term treatment failure.

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