December 2019 Volume 15, Issue 12, Supplement 6 A SPECIAL MEETING REVIEW EDITION Highlights From the 2019 Advances in Inflammatory Bowel Diseases Conference A Review of Selected Presentations From the 2019 AIBD Conference • December 12-14, 2019 • Orlando, Florida Special Reporting on: • A Practical Approach to Anti-Interleukins in IBD 2020 • Update: ACG Guidelines for the Treatment of Crohn’s Disease • Management of Ulcerative Colitis in Adults: ACG Clinical Guidelines • The Road Ahead: Potential Benefits and Risks of Combining Biologics and Novel Agents • A Practical Approach to JAK inhibitors in IBD 2020 • A Practical Approach to Anti-Integrins in IBD 2020 • A Practical Approach to Anti-TNFs in IBD 2020 PLUS Meeting Abstract Summaries With Expert Commentary by: Gary R. Lichtenstein, MD Professor of Medicine Director, Center for Inflammatory Bowel Disease University of Pennsylvania Health System Hospital of the University of Pennsylvania Philadelphia, Pennsylvania ON THE WEB: gastroenterologyandhepatology.net Indexed through the National Library of Medicine (PubMed/Medline), PubMed Central (PMC), and EMBASE T:8.125" S:7.125" T:10.875" S:9.875" NOW APPROVED FOR A NEW INDICATION Learn more at StelaraHCP.com © Janssen Biotech, Inc. 2019 10/19 cp-108558v1 Date: November 18, 2019 8:16 AM Brand: STELARA® Colors: CMYK File Name: cp-108558v1_838723_v1 Size: 8 1/8 “ x 10 7/8” 85, 100, 9, 0 = Customer Code: cp-108558v1 Description: NOW APPROVED FOR A NEW INDICATION 49, 0, 21, 0 = Pub: AIBD Gastro & Hepatology and Gastro & Hepatology 2, 3, 96, 7 = We Are Alexander #: 838723 (December 2019 issues) HIGHLIGHTS FROM THE 2019 ADVANCES IN INFLAMMATORY BOWEL DISEASES CONFERENCE A Practical Approach to Anti-Interleukins in IBD 2020 r Bruce E. Sands discussed with ustekinumab (90 mg either every was associated with significantly higher the use of anti-interleukins.1 8 weeks or every 12 weeks) or placebo. corticosteroid-free remission rates at Ustekinumab is the only In both the UNITI-1 and week 44. This rate was 46.9% with the Danti-interleukin agent approved for UNITI-2 trials, a significantly higher every-8-week regimen, 42.6% with the the treatment of patients with IBD. proportion of patients who were treated every-12-week regimen, and 29.8% Through recognition of the shared with ustekinumab compared with pla- with placebo (P=.004 for the compari- p40 protein subunit, ustekinumab can cebo achieved the primary endpoint of son of every 8 weeks vs placebo; P=.035 disrupt proinflammatory cytokines clinical response (defined as a decrease for the comparison of every 12 weeks interleukin (IL) 12 and 23 signalling. of ≥100 points in the Crohn’s Disease vs placebo). In a long-term follow-up In patients with Crohn’s disease, the Activity Index [CDAI] from baseline of the UNITI studies, the rate of remis- pivotal induction trials establishing to week 6, or a CDAI score <150). In sion at 2 years among patients receiving the safety and efficacy of ustekinumab UNITI-1, the rates of response at week ustekinumab every 8 weeks was 47%, were UNITI-1 and UNITI-2.2 The 6 were 34.3% in the 130 mg arm and or 88% of the remission rate observed use of ustekinumab in the mainte- 33.7% in the 6 mg/kg arm, vs 21.5% at 1 year (53.1%; Figure 1).3 nance setting was established by the with placebo (P≤.003 for both com- Among patients with ulcerative IM-UNITI trial.2 In the UNITI-1 parisons with placebo). In UNITI-2, colitis, UNIFI was the pivotal induc- and UNITI-2 trials, patients were the rates of response at week 6 were tion and maintenance trial establishing randomly assigned to receive a single 51.7%, 55.5%, and 28.7%, respec- the safety and efficacy of ustekinumab intravenous dose of ustekinumab tively (P≤.001 for both comparisons in these settings.4 The trial randomly (either 130 mg or approximately 6 with placebo). assigned 961 patients with moderate to mg/kg) or placebo. The UNITI-1 trial The primary endpoint for the severe ulcerative colitis to ustekinumab enrolled 741 patients with a primary or IM-UNITI maintenance trial—remis- (130 mg or ~6 mg/kg) or placebo. secondary nonresponse to anti–tumor sion at week 44 (defined as a CDAI Patients with a response to induction necrosis factor (TNF) therapy, or score <150)—was also higher with therapy were randomly assigned again who developed unacceptable toxicity ustekinumab than placebo. This rate was to receive subcutaneous maintenance after treatment with these agents. The 53.1% with ustekinumab given every 8 injections of ustekinumab (90 mg UNITI-2 trial enrolled 628 patients weeks and 48.8% with ustekinumab every 8 weeks or every 12 weeks) or with an inadequate response to con- given every 12 weeks, vs 35.9% with placebo. ventional therapy or who were intoler- placebo (P=.005 for the comparison The primary endpoint of clinical ant to it. Patients with a response in of every 8 weeks vs placebo; P=.04 for remission was defined as a total score either UNITI-1 or UNITI-2 (n=397) the comparison of every 12 weeks vs of 2 or less on the Mayo scale and no were randomly assigned to treatment placebo). Treatment with ustekinumab subscore exceeding 1 on any of the 70 53% 47% of patients in remission of patients in remission 52 weeks after induction 60 100 weeks after induction 50 40 30 20 Placebo (n=131) Ustekinumab 90 mg every 8 weeks (n=128) Proportion of Patients (%) Proportion of Patients 10 Entry into long-term extension 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 Entry into maintenance from Weeks After Induction 8-week induction Figure 1. Remission through 2 years among patients with Crohn’s disease responding to induction treatment with ustekinumab in the IM-UNITI long-term extension study. Adapted from Sands BE et al. ACG abstract 49. Presented at: American College of Gastroenterology Annual Scientific Meeting; October 5-10, 2018; Philadelphia, PA3 and Sands BE. A practical approach to anti-interleukins in IBD 2020. Paper presented at: Advances in Inflammatory Bowel Diseases Conference; December 12-14, 2019; Orlando, Florida.1 Gastroenterology & Hepatology Volume 15, Issue 12, Supplement 6 December 2019 3 SPECIAL MEETING REVIEW EDITION 4 Mayo scale components. The rate 100 P<.001 of clinical remission at week 8 was P<.001 15.6% with ustekinumab at 130 mg, 80 71.0 15.5% with ustekinumab at 6 mg/kg, 68.0 and 5.3% with placebo (P<.001 for 60 both comparisons to placebo). Among 44.6 responding patients, the rate of clini- 40 cal remission at week 44 was 43.8% with ustekinumab given every 8 weeks, 20 38.4% with ustekinumab given every 12 weeks, and 24.0% with placebo Proportion of Patients (%) Proportion of Patients 78/175 117/172 125/176 0 (P=.002 and P<.001, respectively). Other outcomes through week 44 are shown in Figures 2 and 3.5 Long-term Placebo SCa Ustekinumab Ustekinumab 90 mg SC q12w 90 mg SC q8w symptomatic remission was observed in the group of patients who continued to receive ustekinumab in a long-term Figure 2. Clinical response through week 44 among patients with ulcerative colitis treated with extension trial.6 a ustekinumab in the UNIFI trial. Patients with a clinical response to intravenous ustekinumab In summary, ustekinumab was and were randomized to subcutaneous placebo upon entry into the maintenance study. q8w, effective in Crohn’s disease and ulcer- every 8 weeks; q12w, every 12 weeks; SC, subcutaneous. Adapted from Sandborn WJ et al. ative colitis, where it may be useful ECCO abstract OP37. J Crohns Colitis. 2019;13(suppl 1)5 and Sands BE. A practical approach in both the first-line setting and after to anti-interleukins in IBD 2020. Paper presented at: Advances in Inflammatory Bowel Diseases Conference; December 12-14, 2019; Orlando, Florida.1 anti-TNF agent failure. Ustekinumab confers a very good corticosteroid spar- ing and maintenance effect. The onset of efficacy associated with ustekinumab Placebo (n=175) was observed as early as 2 weeks, but Ustekinumab, 90 mg every 12 weeks (n=172) efficacy can increase over 16 weeks and beyond. The safety of ustekinumab has Ustekinumab, 90 mg every 8 weeks (n=176) been well established, with minimal immunogenicity and a minimal need P=.07 for laboratory monitoring. 100 References 90 P=.01 1. Sands BE. A practical approach to anti-interleukins in IBD 2020. Paper presented at: 2019 Advances in 80 65 Inflammatory Bowel Diseases Conference; December 70 (n=40) 58 12-14, 2019; Orlando, Florida. (n=38) 2. Feagan BG, Sandborn WJ, Gasink C, et al; UNITI– 60 IM-UNITI Study Group. Ustekinumab as induction 38 and maintenance therapy for Crohn’s disease. N Engl J 50 Med. 2016;375(20):1946-1960. (n=45) 3. Sands BE, Kramer BC, Gasink C, et al. Long-term 40 efficacy and safety of ustekinumab with and without 30 concomitant immunosuppressants for Crohn’s disease: results from IM-UNITI long-term extension through 20 two years. Presented at: American College of Gastro- Patients at Week 44 (%) Week at Patients enterology Annual Scientific Meeting; October 5-10, 10 2018; Philadelphia, PA. Abstract 49. 4. Sands BE, Sandborn WJ, Panaccione R, et al; UNIFI 0 Study Group. Ustekinumab as induction and main- Remission Through Week 44 tenance therapy for ulcerative colitis. N Engl J Med. 2019;381(13):1201-1214. Among Those in Remission 5. Sandborn WJ, Sands BE, Panaccione R, et al.