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P1415 - Relationship Between Protocol Specified Corticosteroid Tapering Regimens and Achieving Outcome Measures in Patients With Moderate-Severe Ulcerative Colitis and Crohn’s Disease

Monday, October 28

10:30 AM - 4:15 PM

Location: Exhibit Halls 3 and 4 (Street Level)

Presenting Author(s)

John George, MD

Bridgeport, Connecticut

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.

Disclosures:

John George indicated no relevant financial relationships.

Siddharth Singh indicated no relevant financial relationships.

Parambir Dulai: Abbvie – Consultant, Grant/Research Support. Janssen – Consultant, Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Takeda – Consultant, Grant/Research Support.

Christopher Ma: AbbVie – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Robarts Clinical Trials, Inc. – Consultant.

Tran Nguyen indicated no relevant financial relationships.

Brian Feagan indicated no relevant financial relationships.

William Sandborn: Abbvie – Consultant, Grant/Research Support. Allergan – Consultant. Amgen – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Atlantic Healthcare Limited – Grant/Research Support. Avexegen Therapeutics – Consultant. BeiGene – Advisory Committee/Board Member, Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Boehringer Ingelheim – Consultant, Grant/Research Support. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Conatus – Consultant. Cosmo Pharmaceuticals – Consultant. Escalier Therapeutics – Advisory Committee/Board Member, Consultant, Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Spouse is employee. Ferring – Consultant. Forbion – Consultant. Genentech – Consultant, Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Gossamer Bio – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Incyte – Consultant. Janssen – Consultant, Grant/Research Support. Kyowa Kirin Pharmaceutical Research – Consultant. Landos Biopharma – Consultant. Lilly – Consultant, Grant/Research Support. Oppilan Pharma – Advisory Committee/Board Member, Consultant, Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Spouse is employee. Opthotech – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Otsuka – Consultant. Pfizer – Consultant, Grant/Research Support, Speaker's Bureau. Precision IBD – Advisory Committee/Board Member, Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Spouse is employee. Progenity – Advisory Committee/Board Member, Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Prometheus Laboratories – Consultant, Grant/Research Support. Reistone – Consultant. Ritter Pharmaceuticals – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Robarts Clinical Trials (owned by Health Academic Research Trust, HART) – Consultant, Grant/Research Support. Series Therapeutics – Advisory Committee/Board Member, Consultant. Shire – Consultant, Grant/Research Support. Sienna Biopharmaceuticals – Consultant. Sigmoid Biotechnologies – Consultant. Sterna Biologicals – Consultant. Sublimity Therapeutics – Consultant. Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Theravance Biopharma – Consultant. Tigenix – Consultant, Grant/Research Support. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Ventyx Biosciences – Consultant, Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Spouse is employee. Vimalan Biosciences – Consultant, Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Spouse is employee. Vivelix Pharmaceuticals – Consultant.

Vipul Jairath indicated no relevant financial relationships.

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.