770 Relationship Between Protocol Specified Corticosteroid Tapering Regimens and Achieving Outcome Measures in Patients With Moderate-Severe Ulcerative Colitis and Crohn's Disease

Abstract

INTRODUCTION: Corticosteroid-free clinical remission is an important clinical outcome, yet is inconsistently defined and reported in clinical trials. We summarized the protocol specified corticosteroid tapering regimens in clinical trials of moderate-severe ulcerative colitis (UC) and Crohn's disease (CD), and calculated differences in rates of clinical remission versus corticosteroid-free clinical remission (CSF-CR). METHODS: Through a systematic literature review through February 28, 2019, we identified 16 randomized controlled trials (RCTs) of biologics or small molecules in patients with moderate-severe UC or CD that reported CSF-CR as an outcome. We estimated relative risk (RR) [and 95% confidence interval (CI)] of achieving CSF-CR vs. overall clinical remission in patients treated with active intervention or placebo, through random effects meta-analysis. RESULTS: Across trials of UC (11 trials) and CD (5 trials), median 53% (range, 28-81%) and 49% (range, 42-56%) participants were on corticosteroids at time of trial entry, respectively. Participants were allowed to enter trials at median corticosteroid dose 35 mg/d (range, 20-40 mg/d). Doses were kept stable for median 8 weeks (range, 5-10 weeks) during induction therapy, after which a mandatory and structured tapered was implemented, albeit with investigators discretion depending on clinical status. For maintenance trials, pooled rates of CSF-CR in patients with UC (n = 11) treated with placebo was 9.7% (95% CI, 6.8-13.6% vs. overall clinical remission: 14.2%; 95% CI, 10.6-18.7) and with CD (n = 5), 19.1% (95% CI, 11.3-30.2 vs. overall clinical remission: 25.7%; 95% CI, 16.4-37.7). In UC trials, the rate of CSF-CR was 24% lower than the rate of overall clinical remission (RR, 0.76; 95% CI, 0.67-0.86; placebo: RR, 0.74; 95% CI, 0.56-0.97). In patients with CD, rate of CSF-CR was 18% lower than rate of overall clinical remission (RR, 0.82; 95% CI, 0.72-0.94; placebo: RR, 0.75; 95% CI, 0.57-0.98). CONCLUSION: This is the first systematic review and meta-analysis to study corticosteroids handling across clinical trials. Protocol specified corticosteroid tapering regimens varies across trials with considerable investigator discretion. Rates of CSF-CR is 20-25% lower than overall clinical remission. These findings will help to inform design and interpretation of future clinical trials and highlight the need for standardization.