Long-term outcomes of immunosuppression - naïve steroid responders following hospitalization for acute severe ulcerative colitis
MetadataShow full item record
INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a severe complication of ulcerative colitis (UC) that is associated with significant morbidity, treatment refractoriness and need for colectomy. Patients who do not adequately respond to the initial intravenous steroid therapy receive medical rescue therapy with infliximab or cyclosporine or undergo surgery for their refractory disease. However, there is limited guidance on management of steroid responders in this setting. While it is well established that Crohn’s disease (CD) is progressive and benefits from early institution of immunosuppressive therapy, such a paradigm is less well established in UC and thresholds for therapy escalation remain poorly defined. In immunosuppression-naïve patients, whether a single hospitalization for ASUC is a sufficient threshold to escalate to immunomodulator or biologic therapy is unknown. METHODS: From a single tertiary referral center, we identified all patients with ASUC hospitalized for intravenous steroids who were immunosuppression naïve (new UC diagnosis, no therapy, or 5-aminosalicylate (5-ASA) therapy) at their index hospitalization. We excluded patients who were refractory to steroids and initiated medical rescue therapy or required surgery during the index hospitalization. Our primary exposure of interest was initiation of biologic therapy within 1 month of hospital discharge or immunomodulator therapy (thiopurine, methotrexate) within 3 months. Our primary outcomes were need for colectomy within 12 months following hospitalization. Secondary outcomes include re-hospitalization rate within 12 months and late colectomy ( between 91-365 days). RESULTS: Our study included a total of 133 immunosuppressive-naïve ASUC patients among whom 56 (42%) escalated therapy to thiopurine (93%) or biologic (7%) post-hospitalization. The median age of the cohort was 29 years (range 16 – 88 years) and 46% were male. 82 patients (62%) had pancolitis on disease distribution. 38% and 58% were noted to have moderate to severe disease on sigmoidoscopic evaluation. Thirteen patients (10%) underwent surgery by 1 year. At 12 months, there was no difference in the rate of colectomy among those with therapy escalation (13%) compared to those who did not undergo such escalation (8%, unadjusted OR= 1.69 p=0.53). This lack of difference remained robust on multivariable regression analysis and propensity score adjusted models (OR 0.90, 95% confidence interval (CI) 0.18 – 4.45). There was no difference in the rates of hospitalization within 1 year (OR 2.24 95% CI 0.16 – 4.22) or in the time to colectomy between the two groups (log-rank p=0.27). CONCLUSION: Immunosuppression-naïve ASUC patients who respond to intravenous steroids remain at high risk for colectomy with 10% (13/133) receiving such surgery within 1 year. Therapy escalation was not associated with a reduction in this risk. There is an important need for larger prospective studies defining the benefit of early therapy escalation in UC, and appropriate thresholds for the same.