ozanimod as induction and maintenance therapy for ulcerative colitis

Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. IMPORTANT SAFETY INFORMATION Contraindications: Patients with clinical response at week 8 continued their blinded regimen during the maintenance period. Prespecified subgroup analyses for the primary end point of clinical remission during the induction period are shown in Figure S3. 2022 Aug;82(12):1303-1313. doi: 10.1007/s40265-022-01762-8. 17. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. Treatment-effect sizes in patients with TNF antagonist exposure were similar to those in patients without such exposure. Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results From the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 13 trials. Aliment Pharmacol Ther 2007;26:779-794. Glucocorticoid-free remission was defined as clinical remission at 52 weeks without receipt of glucocorticoids for at least 12 weeks. Efficacy requires further assessment in larger trials. Among the 457 patients who had a response to ozanimod during the induction period and underwent subsequent randomization in the maintenance period, 37.0% in the ozanimod group and 18.5% in the placebo group had clinical remission at week 52 (P<0.001) (Figure 2B). Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Neurology 2010;75:403-410, 12. Expand PDF Save Alert An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis P values reported for analyses other than the primary outcome of clinical remission at week 8 are considered to be nominal and not significant. A Phase 2b Randomized, Double-blind, Active-and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Induction and Maintenance Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis. Together they form a unique fingerprint. Scott FL, Clemons B, Brooks J, et al. The modified intention-to-treat population included all patients who underwent randomization and received at least one dose of ozanimod or placebo. The body-mass index is the weight in kilograms divided by the square of the height in meters. Zeposia (ozanimod) is an oral, sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. 2022 May;56(5):592-599. doi: 10.1177/10600280211041907. Ulcerative colitis is a chronic disease that is characterized by a dysregulated immune response and chronic inflammation in the colonic mucosa. 2022 May;162(6):1767-1769. doi: 10.1053/j.gastro.2021.12.235. Li M, Zhang R, Xin M, Xu Y, Liu S, Yu B, Zhang B, Liu J. Metabolites. journal = "New England Journal of Medicine". The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety. (%), Had a secondary nonresponse no./total no. The incidence. Randomization and Follow-up of the Patients in the Induction and Maintenance Periods. Am J Gastroenterol 2019;114:384-413. Efficacy analyses were based on all patients who underwent randomization and received at least one dose of ozanimod or placebo (modified intention-to-treat population). 2022 Jan;7(1):28-37. doi: 10.1016/S2468-1253(21)00295-8. A missing-at-random assumption was not considered to be appropriate for the data. and Feagan, {Brian G.} and Geert D'Haens and Wolf, {Douglas C.} and Igor Jovanovic and Hanauer, {Stephen B.} NEW! The use of orally administered small molecules as alternatives to injectable monoclonal antibodies for the treatment of ulcerative colitis has both advantages and disadvantages. Percentages of patients with each end point (as well as the numbers and total numbers of patients) are shown, and between-group differences are shown in percentage points with 95% confidence intervals (CI). Curr Gastroenterol Rep. 2022 Dec;24(12):157-170. doi: 10.1007/s11894-022-00853-6. Rosen H, Gonzalez-Cabrera PJ, Sanna MG, Brown S. Sphingosine 1-phosphate receptor signaling. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. and transmitted securely. Patients were assessed on day 1 (baseline), at weeks 4 and 8 (during the induction period), and at weeks 20 and 32 (during the maintenance period). Lancet 2018;391:1263-1273. Gut 2000;47:404-409. Editorial assistance was funded by Bristol Myers Squibb. 14. DOI: 10.1056/NEJMoa1513248, Tap into groundbreaking research and clinically relevant insights. A complete list of the members of the True North Study Group is provided in the Supplementary Appendix, available at NEJM.org. One patient in the placebo group and one in the group assigned to receive 0.5 mg of ozanimod did not receive the assigned regimen and were excluded from the analysis. The site is secure. An official website of the United States government. Initial Real-World Experience From a . Kappos L, Bar-Or A, Cree BAC, et al. Ozanimod, a selective sphingosine-1- phosphate receptor modulator . the efficacy of ozanimod for induction and maintenance for moderately to severely active uc was examined in the phase 2 touchstone trial. S2). Efficacy Results for Ozanimod as Induction and Maintenance Therapy, as Compared with Placebo (Modified Intention-to-Treat Population). Cohen JA, Arnold DL, Comi G, et al. Analysis in the induction period was based on the two-sided CochranMantelHaenszel test and stratified according to glucocorticoid use at screening and previous use of a TNF antagonist. Colombel JF, Rutgeerts P, Reinisch W, et al. ); and IRCCS Humanitas Research Hospital and University Vita-Salute San Raffaele, Milan (S.D.). Intest Res 2018;16:26-42. The Memory T Cell "Communication Web" in Context with Gastrointestinal Disorders-How Memory T Cells Affect Their Surroundings and How They Are Influenced by It. The key secondary efficacy end points were assessed in a closed, prespecified hierarchical testing procedure. The European Commission (EC) has has granted a marketing authorisation for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.. Zeposia, an oral medication taken once daily and made by Bristol Myers Squibb, is a . N Engl J Med 2016;374:1754-1762. Ozanimod treatment was shown to be more effective at inducing clinical remission than placebo for patients with ulcerative colitis. All the authors had full access to the data. The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Analysis in the maintenance period was based on the two-sided CochranMantelHaenszel test and stratified according to clinical remission status at week 10 of the induction period and glucocorticoid use at week 10 of the induction period. Epub 2022 Nov 3. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Clinical response (decrease in Mayo Clinic score of 3 points and 30% and decrease in rectal-bleeding subscore of 1 point or a subscore 1) at 8 weeks occurred in 57% of those receiving 1 mg of ozanimod and 54% of those receiving 0.5 mg, as compared with 37% of those receiving placebo. Safety results were summarized descriptively for all patients who received at least one dose of ozanimod or placebo (safety population). From the University of California San Diego, La Jolla (W.J.S. 2016 May 5;374(18):1754-62. doi: 10.1056/NEJMoa1513248. Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Lfberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. Safety was also assessed. Ozanimod for treating moderately to severely active ulcerative colitis (TA828) Evidence-based recommendations on ozanimod (Zeposia) for treating moderately to severely active ulcerative colitis in adults when conventional or biological . Li X, Zhang H, Zheng W, Sun J, Wang L, He Z. Mol Neurobiol. Utrecht, the Netherlands: Celgene Distribution B.V., 2020 (summary of product characteristics). 30. N Engl J Med, 374 (2016), pp. Aim: The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA). From December 2012 through April 2015, we conducted this randomized, double-blind, placebo-controlled phase 2 trial of induction and maintenance therapy at 57 centers in 13 countries. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Randomization was conducted by means of a centralized interactive voice- and Web-based activated response system (IxRS). ); Yale School of Medicine, New Haven, and the Veterans Affairs Connecticut Healthcare System, West Haven both in Connecticut (L.L. Sensitivity analyses were conducted for the primary and first key secondary end points with the use of an observed-cases analysis (assumption of data missing completely at random) and with the use of multiple imputation (assumption of data missing at random).23. Ords I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Lancet 2022 399 ( 10341 ): 2113 - 2128 . Lancet 2012;380:1606-1619, 2. Macular edema occurred in 3 patients receiving ozanimod; all cases resolved after treatment discontinuation (Table 2). The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12, with higher values indicating more severe disease18; subscores range from 0 to 3, with higher scores indicating more severe disease. Information, resources, and support needed to approach rotations - and life as a resident. N Engl J Med 2005;353:2462-2476, 20. Clipboard, Search History, and several other advanced features are temporarily unavailable. Gastroenterology. The most common adverse events overall were anemia and headache. Methods We conducted a phase 3, multicenter,. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. Marsolais D, Rosen H. Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules. Elevated liver aminotransferase levels were more common with ozanimod. 8600 Rockville Pike Even more important, avoidance of sensitization with the formation of antidrug antibodies has the potential to eliminate one of the most important reasons for the failure of treatment with monoclonal antibodies. N Engl J Med 2021; 385 (14) 1280-1291 The first two trials (OCTAVE 1 and 2) randomly assigned patients to treatment groups of 10 mg tofacitinib twice a day (n = 476 and 439, respectively) or a placebo (n = 122 . The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). Epub 2021 Aug 22. Ozanimod is a sphingosine 1-phosphate receptor modulator marketed under the brand name Zeposia . 10. Efficacy results among the patients in cohort 2 were similar to the results among the patients treated with ozanimod in cohort 1 (Table S3). Acta Neurol Belg 2017;117:821-827. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg . Bradycardia, cardiac conduction abnormalities (second-degree and higher atrioventricular block), macular edema, cancer, serious or opportunistic infection, pulmonary effects, and hepatic effects were examined as adverse events of special interest on the basis of previous associations with S1P receptor modulation.21,22 Clinical laboratory measurements were performed at a central laboratory. Safety was also assessed. The absolute lymphocyte count decreased by a mean of approximately 54% from baseline to week 10 in patients who received ozanimod. Demographic characteristics and disease characteristics at baseline were compared with the use of descriptive statistics. The plan specified that formal testing would stop if the results were not significant, and all subsequent analyses would be considered to be exploratory and the corresponding P values nominal. The members of the steering committee designed the trial in collaboration with the sponsor (Bristol Myers Squibb). Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. / True North Study Group. Gastroenterol Hepatol (N Y). Benefits of High Versus Low Dose Upadacitinib as Maintenance Treatment in Ulcerative Colitis Patients Who Were Responders to 8-week Induction With Upadacitinib: Results From the U . 13. The group names indicate whether the patients received ozanimod or placebo during the maintenance period only; all the patients in the maintenance period had received ozanimod during the induction period. Nat Rev Gastroenterol Hepatol 2020;17:1-2. 1. 2021;385(14):1280-1291. All the ranked key secondary end points were also significantly improved with ozanimod therapy, as compared with placebo, at week 52; improvement in the incidence of histologic remission (an additional secondary end point) also occurred with ozanimod therapy (Figure 2B and Tables S4 and S6). Primary nonresponse was defined as signs and symptoms of persistently active disease despite an adequate trial of induction treatment with an anti-TNF agent. METHODS We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Absolute lymphocyte counts of less than 200 cells per cubic millimeter occurred in 1.1% of the patients who received ozanimod (in cohort 1 or 2) and in no patients who received placebo during the induction period. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. ZEPOSIA (ozanimod) is indicated for the treatment of: 1. Sandborn WJ, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Liu WJ, Petersen A, Charles L, Huang V, Usiskin K, Wolf DC, D'Haens G. J Crohns Colitis. We anticipated that 10% of the patients in the placebo group would have clinical remission after induction therapy. @article{65919f183c004061ac6949cedcbae8f5. Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis. Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study. Bookshelf *Plusminus values are means SD. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. FASEB J 2004;18:551-553, 8. ); APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland (S.G.); Bristol Myers Squibb, Princeton, NJ (A.P., S.Y.H., J.H.L., L.C., D.C., K.U. Results were similar between the treatment/placebo and open-label arms. Demographic and Clinical Characteristics of the Patients at Baseline in the Induction Period (Modified Intention-to-Treat Population). Presented at the Annual Meeting of the European Committee for Treatment and Research in Multiple Sclerosis, Stockholm, September 1113, 2019. abstract. Gordon JP, McEwan PC, Maguire A, Sugrue DM, Puelles J. Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohns disease: a systematic review and clinician surveys. The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). 21. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). The disease characteristics at baseline were similar among the three groups (Table 1). No important differences were observed in subgroup analyses that were based on demographic characteristics and disease characteristics at baseline (Fig. 29. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. 2022 Jan 13;386(2):194. doi: 10.1056/NEJMc2117224. Nat Immunol 2007;8:1295-1301, 7. First, in cohort 1, patients were randomly assigned in a 2:1 ratio to receive ozanimod hydrochloride at a dose of 1 mg per day (equivalent to 0.92 mg of ozanimod; referred to hereafter as ozanimod) or matched placebo once daily in a double-blind manner. To control for multiple comparisons, a closed hierarchical procedure was used for the primary and secondary outcomes. Epub 2022 Feb 2. A documented presence of varicellazoster virus IgG antibody or complete varicellazoster vaccination at least 30 days before randomization was also required. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. 2022 Nov 7;28(41):5893-5909. doi: 10.3748/wjg.v28.i41.5893. 16. The primary outcome occurred in 16% of the patients who received 1 mg of ozanimod and in 14% of those who received 0.5 mg of ozanimod, as compared with 6% of those who received placebo (P=0.048 and P=0.14, respectively, for the comparison of the two doses of ozanimod with placebo). Mayo Clinic scores range from 0 to 12, with higher values indicating more severe disease; subscores range from 0 to 3, with higher scores indicating more severe disease. 1. government site. PDF | On Dec 5, 2022, Benjamin Misselwitz and others published Sphingosin-1-Phosphat-Rezeptor-Modulatoren bei Colitis ulcerosa - Game Changer oder einer unter vielen?Modulateurs du rcepteur de . Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. 19. The members of the steering committee (see the Supplementary Appendix, available at NEJM.org) designed the trial in collaboration with the sponsor (Receptos). This site needs JavaScript to work properly. Elevated liver aminotransferase levels were more common with ozanimod therapy than with placebo. All the authors had full access to the data. Positive topline results were announced from the phase 3 True North trial evaluating the efficacy of ozanimod as an induction. The three-component Mayo score is defined as the sum of the rectal-bleeding subscore, the stool-frequency subscore, and the endoscopy subscore; overall scores range from 0 to 9 (with each subscore ranging from 0 to 3), with higher scores indicating greater activity. Croft NM, Faubion WA Jr, Kugathasan S, Kierkus J, Ruemmele FM, Shimizu T, Mostafa NM, Venetucci M, Finney-Hayward T, Sanchez Gonzalez Y, Bereswill M, Lazar A, Turner D. Lancet Gastroenterol Hepatol. 25. The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12, with higher scores indicating more severe disease; subscores range from 0 to 3, with higher scores indicating more severe disease. Tran JQ, Hartung JP, Peach RJ, et al. Ozanimod: A Review in Ulcerative Colitis. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. 2022 Aug;18(8):453-465. Esophageal lichen planus: Current knowledge, challenges and future perspectives. Treatment with ozanimod led to significant improvements, as compared with placebo, in the incidence of clinical remission (primary end point) and in all key secondary clinical, endoscopic, and histologic end points at weeks 10 and 52. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. 2021;385:1280-1291. Confidentiality agreements were in place between the sponsor and all the authors. Blood samples were obtained at each visit for clinical chemical and hematologic studies and for the measurement of the C-reactive protein concentration. The most frequent events were defined as those that occurred in at least 3% of the patients who received ozanimod during the induction or maintenance period. All the authors had full access to the data. Elevated liver aminotransferase levels were more common with ozanimod. Jangi S, Yoon H, Dulai PS, et al. N Engl J Med. Overall, our results were consistent with safety findings that have previously been reported regarding ozanimod therapy in phase 3 trials involving patients with multiple sclerosis.12,14,15, Our trial design was informed by the increasing use of rigorous therapeutic targets beyond symptom control and endoscopic improvement in patients with ulcerative colitis, such as mucosal healing (requiring both endoscopic and histologic improvement) and reduced use of glucocorticoids.27-30 For example, we required that the definition of mucosal healing include the absence of mucosal neutrophils, which has been associated with a reduced incidence of colectomy, hospitalization, and glucocorticoid use.30,31 We also defined glucocorticoid-free remission as clinical remission at week 52 without glucocorticoid use for at least 12 weeks because relapse within 12 weeks after the discontinuation of glucocorticoid therapy is a defining characteristic of patients with ulcerative colitis in whom the glucocorticoid dose cannot be reduced beyond a certain threshold without relapse occurring.32. The most common reason for discontinuation in the maintenance period was disease relapse (in 31 patients [13.5%] in the ozanimod group and in 77 [33.9%] in the placebo group). ZEPOSIA (ozanimod) is indicated for the treatment of: 1. Gastrointest Endosc 2018;88:887-898. Safety Findings in Induction and Maintenance Phases, According to Trial Group. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). Matloubian M, Lo CG, Cinamon G, et al. Ozanimod for the Treatment of Ulcerative Colitis. With respect to the advantages, the convenience of oral administration is attractive to patients and providers. The members of the steering committee designed the trial in collaboration with the sponsor (Bristol Myers Squibb). 2022 May;18(5):265-271. The most common reasons for ineligibility were disease criteria not met (in 18.1% of the patients who underwent screening), a lack of documentation of varicellazoster virus IgG antibodies or vaccination (in 5.7%), inability to provide informed consent or to comply with protocol assessments (in 4.6%), and presence of Clostridium difficile or other stool pathogens (in 3.7%). Maintenance of remission was defined as clinical remission at 52 weeks in the subgroup of patients with remission at week 10. Fingolimod-associated macular edema: incidence, detection, and management. eCollection 2022. Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P subtypes 1 and 5 (S1P1 and S1P5), leading to internalization of S1P1 receptors in lymphocytes and the prevention of lymphocyte mobilization to inflammatory sites. Moderately to severely active ulcerative colitis (UC) in adults. ), and Receptos, San Diego (H.S., M.C., P.A.F., R.A., S. Gujrathi, A.O.) 1,2 During the 10-week induction period, patients in cohort 1 were randomly assigned in a 2:1 ratio to receive daily ozanimod hydrochloride (1 mg, equivalent to 0.92 mg . CONCLUSIONS Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Ozanimod has recently received US Food and Drug Administration approval for moderate-to-severe ulcerative colitis. A total of 186 of the 197 patients (94%) completed the induction period. 4. Treatment of acute severe colitis remains a clinical challenge, and although many patients respond to cyclosporine therapy, there remains a relative paucity of maintenance options. The most advanced way to teach, practice, and assess clinical reasoning skills. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. Epub 2021 Jun 19. Exploratory outcomes included clinical response, clinical remission, mucosal healing, and change in the Mayo Clinic score at week 32 and histologic remission (Geboes score <2, on a scale from 0 to 5, with higher scores indicating more severe histologic inflammation)21 at weeks 8 and 32. N Engl J Med 2010;362:402-415, 10. Prespecified subgroup analyses for the primary end point of clinical remission during the maintenance period are shown in Figure S5. Neurology 2008;71:1261-1267, 11. CONCLUSIONS Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.". The protocol, available with the full text of this article at NEJM.org, was approved by the institutional review board at each center. Ozanimod is a novel, oral, small-molecule S1P 1 and S1P 5 agonist, mainly S1P 1. Safety Findings through the Final Safety Visit in the Induction and Maintenance Periods. N Engl J Med. conducted a 52-week, phase 3 trial to evaluate ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Patients who did not proceed to the maintenance period were considered not to have had a response at week 32. Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant; therefore, the hierarchical testing plan deemed the analyses of secondary outcomes exploratory. 2. Ozanimod is a small molecule drug that selectively targets S1P receptors 1 and 5 which play a crucial role in lymphocyte trafficking and has been shown to induce a reversible lymphopenia which correlates with response to therapy. Patients were randomly assigned, in a 1:1:1 ratio, to receive oral ozanimod at a dose of 0.5 mg or 1 mg (the choice of these doses was based on modeling of preclinical and phase 1 data) or placebo, once daily. Sandborn et al. Cohort 2 (with a planned sample of 300 patients) was used to ensure that the trial would have an enrollment of 400 patients in the maintenance period, with the trial having 90% power for the primary end point. Finally, the trial was limited to patients receiving ozanimod as monotherapy or in combination with glucocorticoids or aminosalicylates. The overall incidence of nonserious infection with ozanimod therapy was similar to that with placebo during the induction period but was higher than that with placebo during the maintenance period (Table 2). During the maintenance period, serious adverse events of hypertensive crisis occurred in 1 patient each in the ozanimod group and the placebo group; neither event resulted in discontinuation of the trial regimen. We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. METHODS We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Gastroenterol Hepatol (N Y). By week 10, 18.4% and 6.0% of the ozanimod and placebo groups achieved clinical remission while on stable corticosteroids, respectively (P <.0001).In the re-randomized maintenance population, 37.0% of the 230 patients in the ozanimod group and 18.5% of the 227 patients in the placebo group achieved clinical . J Crohns Colitis 2008;2:1-23. Four patients who received ozanimod (one patient who received 0.5 mg and three who received 1 mg) had an increase in the alanine aminotransferase level of more than 3 times the upper limit of the normal range during treatment. Ozanimod previously demonstrated efficacy and tolerable safety in patients with moderate to severe UC for up to 32 weeks in the phase II TOUCHSTONE study. We conducted this randomized, double-blind, placebo-controlled trial at 285 sites in 30 countries. A total of 184 patients (80.0%) who had been assigned to receive ozanimod and 124 (54.6%) who had been assigned to receive placebo completed the maintenance period. The authorized source of trusted medical research and education for the Chinese-language medical community. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. Laboratory values were flagged by the central laboratory if they fell outside the standard reference range. Clinical remission was defined as follows: a rectal-bleeding subscore of 0; a stool-frequency subscore of 1 or less, with a decrease of at least 1 point from baseline; and an endoscopy subscore of 1 or less (all on scales from 0 [none] to 3 [most severe]).19. Background: Wolf DC, Colombel J-F, Ponich T, et al. Cohen JA, Arnold DL, Comi G, et al. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. A total of 199 patients were randomly assigned to the trial groups, of whom 197 received placebo or ozanimod (Fig. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). Careers. Drugs. Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 study. Results of sensitivity analyses of the primary end point (during both the induction and maintenance periods) were consistent with those of the primary analysis (Table S5). USA: A recent study in the New England Journal of Medicine reported ozanimod to be more effective than placebo for the treatment of patients with moderately to severely active ulcerative colitis. Talquetamab, a T-CellRedirecting GPRC5D Bispecific Antibody for Multiple Myeloma, A Covid-19 Milestone Attained A Correlate of Protection for Vaccines, A Step toward Interoperability of Health IT, Breakthrough Infections after Postexposure Vaccination against Mpox, Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma, Case 37-2022: A 55-Year-Old Man with Fatigue, Weight Loss, and Pulmonary Nodules, Brief Report: In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompes Disease, NEJM Catalyst Innovations in Care Delivery. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Panel B shows the percentage of patients who had a clinical response (defined as a reduction from baseline in the Mayo Clinic score of 3 points and 30%, and a decrease from baseline in the rectal-bleeding subscore of 1 point or an absolute rectal-bleeding subscore of 1 point) at week 8. At week 32, the rate of clinical remission was 21% in the group that received 1 mg of ozanimod, 26% in the group that received 0.5 mg of ozanimod, and 6% in the group that received placebo; the rate of clinical response was 51%, 35%, and 20%, respectively. Statistical comparisons of efficacy end points for the induction period were performed in cohort 1 only. Vermeire S, Lakatos PL, Ritter T, Hanauer S, Bressler B, Khanna R, Isaacs K, Shah S, Kadva A, Tyrrell H, Oh YS, Tole S, Chai A, Pulley J, Eden C, Zhang W, Feagan BG; LAUREL Study Group. Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease. This potent. Treatment with oral aminosalicylates or prednisone (30 mg per day) was required to be at stable doses. The induction portion of TUSCANY-2 is complete, and the maintenance portion remains ongoing. MeSH and transmitted securely. METHODS We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Research output: Contribution to journal Article peer-review. Grler MH, Goetzl EJ. The time to disease relapse was examined as an exploratory end point. European evidence-based consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis. 3. 2. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Multiple sclerosis treatment with fingolimod: profile of non-cardiologic adverse events. Sandborn WJ, Feagan BG, D'Haens G et al (2022) Ozanimod as induction and maintenance therapy for ulcerative colitis. Dive into the research topics of 'Ozanimod as induction and maintenance therapy for ulcerative colitis'. title = "Ozanimod as induction and maintenance therapy for ulcerative colitis". Accessibility Future studies are needed to assess the risk of infections associated with ozanimod. ); Academic Medical Center, Amsterdam (G.D.); University Hospital Gasthuisberg, Leuven, Belgium (S.V. A complete list of investigators in the TOUCHSTONE trial is provided in the Supplementary Appendix, available at NEJM.org. In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The trial was conducted from May 2015 through June 2020. Science 2002;296:346-349, 6. Macular edema occurred in 3 patients receiving ozanimod; all cases resolved after treatment discontinuation (, Presented at the Annual Meeting of the European Committee for Treatment and Research in Multiple Sclerosis, Presented at the Triennial Joint Meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (MSVirtual2020), Case Records of the Massachusetts General Hospital, Talquetamab, a T-CellRedirecting GPRC5D Bispecific Antibody for Multiple Myeloma, A Covid-19 Milestone Attained A Correlate of Protection for Vaccines, A Step toward Interoperability of Health IT, Breakthrough Infections after Postexposure Vaccination against Mpox, Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma, Case 37-2022: A 55-Year-Old Man with Fatigue, Weight Loss, and Pulmonary Nodules, Brief Report: In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompes Disease, NEJM Catalyst Innovations in Care Delivery, Time since diagnosis of ulcerative colitis yr, Had a primary nonresponse no./total no. Patients may be classified under more than one response category if they had received more than one previous anti-TNF therapy and had a different response to each therapy. 2021 Sep 30;385(14):1280-1291. The time to disease relapse (an exploratory end point) during the maintenance period is shown in Figure S4. 32. 6. Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant; therefore, the hierarchical testing plan deemed the analyses of secondary outcomes exploratory. We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Selmaj KW, Steinman L, Comi G, et al. Ellen J. Scherl, MD, reviews data from the phase 3 True North study evaluating the use of ozanimod as induction and maintenance therapy for moderate to severe ulcerative colitis, and the panel shares their experience with ozanimod in clinical practice. Panel D shows the percentage of patients with histologic remission (Geboes score <2, on a scale from 0 to 5, with higher scores indicating more severe histologic inflammation) at week 8. Once the percentage of patients with previous exposure to a tumor necrosis factor (TNF) antagonist reached 30% in cohort 1, the IxRS assigned patients with TNF antagonist exposure to cohort 2, in which patients received open-label ozanimod at the same daily dose. 2022 Jun;162(7):2104-2106. doi: 10.1053/j.gastro.2022.01.033. All the authors had full access to the data. Abnormal liver-function tests led to the discontinuation of ozanimod therapy in 3 of 796 patients (0.4%) in the induction period and in 1 of 230 patients (0.4%) in the maintenance period. Treatment with ozanimod was shown to have a significantly higher clinical response during induction and maintenance of ulcerative colitis. 28. 11. C-reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Information and tools for librarians about site license offerings. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Lancet Gastroenterol Hepatol. MeSH Mult Scler 2014;20:471-480, 13. The first author wrote the first draft of the manuscript. L Kappos, A Bar-Or, BAC Cree, et al. Pai RK, Jairath V, Vande Casteele N, Rieder F, Parker CE, Lauwers GY. J Clin Pharmacol 2017;57:988-996. Results from the first-in-human study with ozanimod, a novel, selective sphingosine-1-phosphate receptor modulator. Sphingosine-1 Phosphate Receptor Modulators: The Next Wave of Oral Therapies in Inflammatory Bowel Disease. doi: 10.1056/NEJMc1607287. Biometrika 1976;63:581-592. Given the nonsignificant findings for the comparison of the remission rate at week 8 in the group that received 0.5 mg of ozanimod with that in the placebo group, all subsequent analyses were considered to be exploratory and the results not significant (nominal P values are provided). Another limitation is the lack of long-term data; the open-label extension phase of this trial is ongoing. Missing data were handled with the use of a nonresponse imputation. At week 8, clinical remission occurred in 11 of 67 patients (16%) who received 1 mg of ozanimod and in 9 of 65 patients (14%) who received 0.5 mg of ozanimod, as compared with 4 of 65 (6%) who received placebo (P=0.048 and P=0.14, respectively, for the comparison of the two doses of ozanimod with placebo) (Figure 1A). The current study consisted of a 10-week. Additional details regarding the statistical analysis are provided in the Supplementary Appendix. Patients were required to have received stable doses of oral aminosalicylates or glucocorticoids (prednisone at a dose of 20 mg per day or budesonide) or both for at least 2 weeks before screening endoscopy and to continue receiving the same dose for the duration of the induction period; the glucocorticoid dose had to be tapered once the patient entered the maintenance period. A total of 645 patients entered cohort 1 and were randomly assigned to receive either ozanimod (429 patients) or placebo (216 patients) in a double-blind manner; 367 patients received open-label ozanimod in cohort 2 (Figure 1). Address reprint requests to Dr. Sandborn at the Division of Gastroenterology, University of California, San Diego, 9500 Gilman Dr., MC 0956, La Jolla, CA 92093-0956, or at [emailprotected]. Cells. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. Authors We aim to describe the trial design of the YELLOWSTONE phase 3 program evaluating the . A 7-day period of dose escalation with ozanimod starting at 0.25 mg on days 1 to 4 and progressing to 0.5 mg on days 5 to 7 and to 1 mg thereafter was incorporated to minimize the risk of bradycardia that has been reported with some S1P modulators within the first few hours after administration.17,18. ZEPOSIA is a sphingosine 1-phosphate receptor modulator indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). Gilenya (package insert). All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. A total of 2 of 4 patients with remission at week 8 in the placebo group, 7 of 9 in the group that received 0.5 mg of ozanimod, and 5 of 11 in the group that received 1 mg of ozanimod still had remission at week 32. N Engl J Med . No cases of second-degree type 2 atrioventricular block or third-degree atrioventricular block occurred. Panel C shows the percentage of patients with mucosal healing (endoscopy subscore of 1 point) at week 8. 1. The percentage of patients with histologic remission (an additional secondary end point) was 10.8 percentage points (95% confidence interval, 5.8 to 15.8) higher with ozanimod than with placebo (Fig. The combined percentage of AEs was highest with infliximab (174.45%,) and least with ozanimod (23.04%) and most commonly belonged to the 'infection and infestation system organ class (SOC)'. Tran JQ, Zhang P, Surapaneni S, Selkirk J, Yan G, Palmisano M. Absorption, metabolism, and excretion, in vitro pharmacology, and clinical pharmacokinetics of ozanimod, a novel sphingosine 1-phosphate receptor agonist. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992. (1) Moderately to severely active ulcerative colitis (UC) in adults. No patient with a serious or opportunistic infection had an absolute lymphocyte count of less than 200 cells per cubic millimeter. We also examined changes from baseline in the absolute lymphocyte count and the concentrations of C-reactive protein, calprotectin, and lactoferrin. In cohort 1, a total of 401 patients (93.5%) who had been assigned to receive ozanimod and 192 (88.9%) who had been assigned to receive placebo completed the induction period. A total of 91 of the 103 patients who entered the maintenance phase (88%) completed the trial. Ozanimod: first approval. BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor modulator currently approved for the treatment of moderately to severely active ulcerative colitis and relapsing multiple sclerosis, showed clinical, endoscopic, and histological benefit in the phase 2 STEPSTONE trial for Crohn's disease (CD). 15. 12. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Bethesda, MD 20894, Web Policies Exploratory Efficacy Outcomes at Week 32 in the Trial of Ozanimod as Maintenance Therapy. Editorial assistance was funded by Bristol Myers Squibb. S3 in the Supplementary Appendix). The protocol, available with the full text of this article at NEJM.org, was approved by the institutional review board at each center. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Before Bradycardia occurred more frequently with ozanimod therapy than with placebo during the induction period but not during the maintenance period. 2,3 zeposia reduces the capacity of lymphocytes to migrate from lymphoid tissue, reducing the number of circulating lymphocytes in peripheral blood and lymphocyte migration into the intestines. UR - http://www.scopus.com/inward/record.url?scp=85116386829&partnerID=8YFLogxK, UR - http://www.scopus.com/inward/citedby.url?scp=85116386829&partnerID=8YFLogxK, Powered by Pure, Scopus & Elsevier Fingerprint Engine 2022 Elsevier B.V, We use cookies to help provide and enhance our service and tailor content. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. DHaens G. Systematic review: second-generation vs. conventional corticosteroids for induction of remission in ulcerative colitis. The .gov means its official. Lee SH, Kwon JE, Cho M-L. Immunological pathogenesis of inflammatory bowel disease. 2021 Sep 30;385(14):1280-1291. doi: 10.1056/NEJMoa2033617. The https:// ensures that you are connecting to the Francis G, Kappos L, OConnor P, et al. In conclusion, in this preliminary trial, ozanimod at a dose of 1 mg was associated with a slightly higher rate of clinical remission among patients with moderately to severely active ulcerative colitis than the rate with placebo. Zeposia. Tables S1 and S2 list the prespecified efficacy end points. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). ); Western University, London, ON, Canada (B.G.F. One patient receiving ozanimod had a hypertensive crisis on day 1 of the induction period; the event was moderate and resolved on the same day without treatment interruption. Nat Rev Drug Discov 2009;8:297-307, 5. Ozanimod (RPC1063) is a new oral S1P1-receptor and S1P5-receptor modulator with no activity on S1P2, S1P3, and S1P4.16 A phase 2 trial of ozanimod in patients with relapsing multiple sclerosis showed a dose-dependent reduction in circulating lymphocytes that was associated with significant reductions in inflammatory and neurodegenerative brain lesions, with minimal effects on heart rate and liver enzymes.17 We evaluated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. Throughout the 52-week trial, 17 patients had an absolute lymphocyte count of less than 200 cells per cubic millimeter, which subsequently increased and remained at a level at or above 200 cells per cubic millimeter during ozanimod treatment. Clinical remission was defined as a rectal-bleeding subscore of 0, a stool-frequency subscore of 1 or less (plus a 1-point reduction from baseline), and a mucosal endoscopy subscore of 1 or less, without friability. Panel A shows the percentage of patients in the three trial groups who had a clinical remission (Mayo Clinic score 2, with no individual subscore >1) at week 8 (the primary outcome). The absence of clinically significant bradycardia or cardiac conduction abnormalities may have been due to mitigation by the 7-day dose-escalation schedule.13-15,24-26 It should be noted that the eligibility criteria for this trial excluded patients with conditions such as recent myocardial infarction, unstable angina or other clinically significant cardiovascular disease, or active or chronic infection. Greater reductions from baseline in fecal calprotectin levels were also observed with ozanimod than with placebo in both the induction and maintenance periods (Table S7). 84 The patients were randomized to placebo, 0.5, or 1 mg of ozanimod daily. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Ozanimod-Dependent Activation of SIRT3/NF-B/AIM2 Pathway Attenuates Secondary Injury After Intracerebral Hemorrhage. HHS Vulnerability Disclosure, Help This article was updated on October 8, 2021, at NEJM.org. Ozanimod as induction and maintenance therapy for ulcerative colitis. Clipboard, Search History, and several other advanced features are temporarily unavailable. (1) Along with the rising prevalence of inflammatory bowel disease (IBD) [Crohn's disease (CD) and ulcerative colitis (UC)], biological therapies need an update/insight.This review included randomized . Nonserious infections were more common with ozanimod than with placebo during the maintenance phase of the trial. Mucosal healing at week 8 occurred in 8 of 65 patients (12%) in the placebo group, as compared with 18 of 65 (28%) in the group that received 0.5 mg of ozanimod (P=0.03) and 23 of 67 (34%) in the group that received 1 mg of ozanimod (P=0.002) (Figure 1C). N1 - Funding Information: Ozanimod-treated patients who had a clinical response (defined as a reduction in the total Mayo score of 3 points and 30% from baseline or in the three-component Mayo score of 2 points and 35% from baseline, as well as a reduction in the rectal-bleeding subscore of 1 point or an absolute rectal-bleeding subscore of 1 point) at week 10 were eligible to undergo randomization again, in a 1:1 ratio, to receive either ozanimod or placebo in a double-blind manner through week 52 (maintenance period). Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results From the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study. At week 32, patients receiving 1 mg of ozanimod continued to have higher rates of clinical remission, clinical response, mucosal healing, and histologic remission, as well as lower Mayo Clinic scores, than those with placebo. Ozanimod effective as induction, maintenance therapy for ulcerative colitis A once-daily oral formulation of ozanimod, a selective sphingosine-1-phosphate (S1P) receptor modulator, outdid placebo as induction and maintenance t. Feagan BG, Sandborn WJ, Danese S, et al. Jain N, Bhatti MT. Safety was also assessed. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis N Engl J Med. No important differences were observed among the groups in the most commonly reported adverse events during the trial (Table 2). The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. 2022 Nov 29;15:17562848221138160. doi: 10.1177/17562848221138160. 1. (HealthDay)For patients with moderately to severely active ulcerative colitis, ozanimod is more effective than placebo as induction and maintenance therapy, according to a study published in . The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Sandborn WJ, Feagan BG, Wolf DC, D'Haens G, Vermeire S, Hanauer SB, Ghosh S, Smith H, Cravets M, Frohna PA, Aranda R, Gujrathi S, Olson A; TOUCHSTONE Study Group. (%), Serious adverse event related to ozanimod or placebo no. Conclusions: Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study. This site needs JavaScript to work properly. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. 4 it is taken orally N Engl J Med 1987;317:1625-1629, 19. The .gov means its official. 5. Eur J Gastroenterol Hepatol 2015;27:804-812. Sandborn WJ, Feagan BG, D'Haens G, Wolf DC, Jovanovic I, Hanauer SB, Ghosh S, Petersen A, Hua SY, Lee JH, Charles L, Chitkara D, Usiskin K, Colombel JF, Laine L, Danese S; True North Study Group. DOI: 10.1056/NEJMoa2033617, Tap into groundbreaking research and clinically relevant insights. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Lancet Neurol 2019;18:1021-1033. Demographic Characteristics and Disease Characteristics at Baseline, According to Trial Group. The ranked secondary end points for the maintenance period (at week 52) were the percentages of patients with a clinical response, endoscopic improvement, maintenance of clinical remission (remission at week 52 in the subgroup of patients with remission at week 10), glucocorticoid-free remission (remission with no glucocorticoid use for 12 weeks), mucosal healing, and durable clinical remission (remission at weeks 10 and 52, assessed in all patients in the maintenance period). Stool samples were obtained at baseline and at weeks 8 and 32 for the measurement of fecal calprotectin and lactoferrin concentrations. Demographic and Clinical Characteristics of the Patients at Baseline in the Induction Period (Modified Intention-to-Treat Population).*. The percentage of patients with TNF antagonist exposure was capped at 50% in cohort 2. ), and the University of Calgary, Calgary, AB (S. Ghosh) all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W. Patients were randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. View Record in Scopus Google Scholar. Several adverse events of special interest that are known to be associated with S1P receptor modulation (e.g., bradycardia, serious or opportunistic infections, macular edema, and elevated liver-enzyme levels) were monitored in the clinical trials.10-15 We report here the results of True North, a 52-week, phase 3 trial to evaluate ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Long-term . The primary outcome was clinical remission (Mayo Clinic score 2, with no subscore >1) at 8 weeks. From the University of California, San Diego, La Jolla (W.J.S. Lancet Gastroenterol Hepatol 2020;5:819-828. ); the Feinberg School of Medicine, Chicago (S.B.H. 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