John George, MD1, Siddharth Singh, MD2, Parambir Dulai, MD2, Christopher Ma, MD3, Tran Nguyen, MS4, Brian G. Feagan, MD, MSc, FACG5, William J. Sandborn, MD, FACG2, Vipul Jairath, BSc, MBChB, PhD, MRCP6
1Yale New Haven Health Bridgeport Hospital, Bridgeport, CT; 2University of California San Diego, La Jolla, CA; 3University of Calgary, Calgary, AB, Canada; 4Robarts Research Institute, London, ON, Canada; 5Robarts Clinical Trials, London, ON, Canada; 6Western University, London Health Sciences Centre, London, ON, Canada
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 35mg/d (range, 20-40mg/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).
Discussion: 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.
Citation: John George, MD; Siddharth Singh, MD; Parambir Dulai, MD; Christopher Ma, MD; Tran Nguyen, MS; Brian G. Feagan, MD, MSc, FACG; William J. Sandborn, MD, FACG; Vipul Jairath, BSc, MBChB, PhD, MRCP. P1415 - RELATIONSHIP BETWEEN PROTOCOL SPECIFIED CORTICOSTEROID TAPERING REGIMENS AND ACHIEVING OUTCOME MEASURES IN PATIENTS WITH MODERATE-SEVERE ULCERATIVE COLITIS AND CROHN’S DISEASE. Program No. P1415. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.