S99 Upadacitinib in the Treatment of Ulcerative Colitis. 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)'. 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. 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. conducted a 52-week, phase 3 trial to evaluate ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. 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.7-9 In a phase 2 trial, treatment with ozanimod showed significant improvements over placebo with regard to endoscopic, histologic, and clinical end points in patients with moderate-to-severe ulcerative colitis.10 A separate phase 2 trial showed benefits with ozanimod therapy in patients with Crohns disease.11 To date, the safety profile of ozanimod, as characterized on the basis of studies involving more than 4000 patients with ulcerative colitis, Crohns disease, or relapsing multiple sclerosis and healthy volunteers, is consistent across populations. MeSH Intest Res 2018;16:26-42. Statistical comparisons of efficacy end points for the induction period were performed in cohort 1 only. 23. Disclaimer, National Library of Medicine Third, ozanimod treatment resulted in large reductions from baseline in absolute lymphocyte counts, with most patients in the group that received 1 mg having counts below the lower limit of the normal range at week 8 a finding that is consistent with the mechanism of the drug. Primary nonresponse was defined as signs and symptoms of persistently active disease despite an adequate trial of induction treatment with an anti-TNF agent. Li M, Zhang R, Xin M, Xu Y, Liu S, Yu B, Zhang B, Liu J. Metabolites. Schroeder KW, Tremaine WJ, Ilstrup DM. Clinical response was defined as a reduction of at least 3 points and of at least 30% from baseline in the total Mayo score or a reduction of at least 2 points and of at least 35% from baseline in the three-component Mayo score, plus a reduction of at least 1 point in the rectal-bleeding score or an absolute rectal-bleeding score of no more than 1 point. We thank the patients and trial site personnel for their involvement; and Traci Stuve, M.A., of Peloton Advantage, an OPEN Health company, for providing writing assistance with an earlier version of the manuscript, with funding from Bristol Myers Squibb. Inflamm Bowel Dis 2008;14:1660-1666. The most trusted, influential source of new medical knowledge and clinical best practices in the world. 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). In the maintenance phase, we typically rely on the drug to maintain the remission that was induced in the initial induction phase. The trial included blinded induction and maintenance periods and an optional open-label period (Fig. Gastroenterology. 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. 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). 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%). Mosli MH, Zou G, Garg SK, et al. (Funded by Receptos; TOUCHSTONE ClinicalTrials.gov number, NCT01647516.). 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. N Engl J Med 1987;317:1625-1629, 19. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. 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. Would you like email updates of new search results? Bianchi Porro G, Cassinotti A, Ferrara E, Maconi G, Ardizzone S. The management of steroid dependency in ulcerative colitis. 21. Safety Findings through the Final Safety Visit in the Induction and Maintenance Periods.*. 19. 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. Sandborn WJ, Feagan BG, D'Haens G et al (2022) Ozanimod as induction and maintenance therapy for ulcerative colitis. Novel Therapies for Patients With Inflammatory Bowel Disease. Patients receiving biologic agents or azathioprine, mercaptopurine, or methotrexate were required to discontinue these agents 5 half-lives before starting the trial regimen and 4 weeks before their screening endoscopy, respectively. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis N Engl J Med. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. All patients included had to have failed prior treatment for ulcerative colitis, and were generally not allowed to be on other ulcerative colitis treatments during the trial. eCollection 2022. 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). Data were collected by a contract research organization (Pharmaceutical Product Development) and analyzed by the sponsor. Ozanimod-Dependent Activation of SIRT3/NF-B/AIM2 Pathway Attenuates Secondary Injury After Intracerebral Hemorrhage. Ords I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. Lancet Neurol 2019;18:1009-1020. Long-term . 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. 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. All the patients had documented presence of varicellazoster virus IgG antibody or complete varicellazoster vaccination at screening. Clipboard, Search History, and several other advanced features are temporarily unavailable. A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. 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. Feagan BG, Sandborn WJ, Danese S, et al. Scores were assessed by a central reader. 25. With respect to the advantages, the convenience of oral administration is attractive to patients and providers. Lancet Gastroenterol Hepatol 2020;5:819-828. Aim: The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA). 17. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Feagan BG, Rutgeerts P, Sands BE, et al. Patients without previous TNF antagonist exposure continued to undergo randomization in cohort 1 until enrollment was closed, at which time such patients were assigned to cohort 2. The first two authors wrote the first draft of the manuscript, and all the authors contributed to subsequent drafts, made a collective decision to submit the manuscript for publication, and vouch for the completeness and veracity of the data and analyses reported and for the adherence of the trial to the protocol. New York: Pfizer Labs, 2018 (package insert). 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. The members of the steering committee designed the trial in collaboration with the sponsor (Bristol Myers Squibb). 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. Sandborn et al. FASEB J 2004;18:551-553, 8. Drugs. 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. 2022 Aug;18(8):453-465. Ozanimod as induction and main-tenance therapy for ulcerative colitis. Confidentiality agreements were in place between the sponsor and all the authors. 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 . 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. 2022 May;18(5):265-271. Finally, the trial was limited to patients receiving ozanimod as monotherapy or in combination with glucocorticoids or aminosalicylates. 8. N Engl J Med, 374 (2016), pp. Overall scores range from 0 to 9 (with each subscore on a scale from 0 to 3), with higher scores indicating greater activity. All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. CONCLUSIONS Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Expand PDF Save Alert An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis Complete resolution of mucosal neutrophils associates with improved long-term clinical outcomes of patients with ulcerative colitis. As noted previously, S1P-receptor modulators have been associated with cardiac and hepatic effects.15 Elevations in hepatic aminotransferase levels were observed in four patients (3%) receiving ozanimod and require further evaluation. official website and that any information you provide is encrypted N Engl J Med. Introduction. 1754-1762. The investigator decided whether the laboratory value qualified as an adverse event. 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). Wolf DC, Colombel J-F, Ponich T, et al. Elevated liver aminotransferase levels were more common with ozanimod. Ozanimod: A Review in Ulcerative Colitis. 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 . HHS Vulnerability Disclosure, Help Patients were excluded from the trial if they had not had a response to induction therapy with at least two biologic agents approved for the treatment of ulcerative colitis, had a clinically relevant cardiac condition, or had a history of uveitis or macular edema. Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease. FOIA DHaens G. Systematic review: second-generation vs. conventional corticosteroids for induction of remission in ulcerative colitis. 15. Sandborn WJ1, Feagan BG1, Wolf DC1, D'Haens G1, Vermeire S1, Hanauer SB1, Ghosh S1, Smith H1, Cravets M1, Frohna PA1, Aranda R1, Gujrathi S1, Olson A1, TOUCHSTONE Study Group Collaborators (101) Sparrow M, Vermeire S, Churchev J, Kotzev I, Takov D, Dragomirov B, Vladimirov B, Lancet Gastroenterol Hepatol. ); the Division of Gastroenterology, University Hospital Medical Center Beanijska Kosa, Belgrade, Serbia (I.J. Clinical remission was analyzed with the use of a two-sided CochranMantelHaenszel test at the 5% significance level, with accounting for stratification according to glucocorticoid use at screening and previous TNF antagonist use for the induction period (week 10) and according to clinical remission status at week 10 and glucocorticoid use at week 10 for the maintenance period (week 52). Ozanimod is a sphingosine-1-phosphate receptor modulator that binds to the 1 and 5 receptor subtypes. 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 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. Acta Neurol Belg 2017;117:821-827. Schwab SR, Cyster JG. We anticipated that 10% of the patients in the placebo group would have clinical remission after induction therapy. Safety was also assessed. Herpes zoster infection did not occur in any patient who did not receive ozanimod. 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). The comparison of 1 mg of ozanimod with placebo was hierarchically ranked before the comparison of 0.5 mg of ozanimod with placebo. 2022 Jan 13;386(2):194. doi: 10.1056/NEJMc2117224. 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. ZEPOSIA (ozanimod) is indicated for the treatment of: 1. DOI: 10.1056/NEJMoa1513248, Tap into groundbreaking research and clinically relevant insights. Safety was also assessed. 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. These results were observed in patients with active disease that had been inadequately controlled by conventional agents, as determined on the basis of required concomitant therapy with aminosalicylates or glucocorticoids at trial entry. Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study. The P values reported for these analyses are considered to be nominal and not significant. 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. 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. The demographic and clinical characteristics of the patients were similar in the two groups (Table 1). Careers. Scott FL, Clemons B, Brooks J, et al. 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. Each subscore category is rated on a scale from 0 to 3, which was summed to give a total Mayo score between 0 and 12; higher scores indicate greater activity.16. Patients underwent dose escalation during the first week after randomization; thereafter, the patients received the randomly assigned dose for 8 weeks (see the Supplementary Appendix). 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). S2 in the Supplementary Appendix). Information and tools for librarians about site license offerings. Publisher Copyright: {\textcopyright} 2015 Inderscience Enterprises Ltd.. All rights reserved.". Ozanimod as induction and maintenance therapy for ulcerative colitis. J Crohns Colitis 2008;2:1-23. The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. We conducted this randomized, double-blind, placebo-controlled trial at 285 sites in 30 countries. Am J Gastroenterol 2015;110:802-819, May 5, 2016N Engl J Med 2016; 374:1754-1762 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. 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). Nonparametric methods were used for analysis of the changes from baseline in the absolute lymphocyte count and the concentrations of C-reactive protein, calprotectin, and lactoferrin. Safety was also assessed. This site needs JavaScript to work properly. Zeposia. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992.). Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. S2). 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). ozanimod (zeposia ) is the first sphingosine-1-phosphate receptor (s1pr) modulator to be approved for the treatment of adults with moderately to severely active ulcerative colitis in the usa, and in adults with moderately to severely active ulcerative colitis who have had an inadequate or lost response to, or were intolerant of, either The eighth and ninth authors, both employees of the sponsor, vouch for the completeness and accuracy of the data, and the eighth author vouches for the adherence of the trial to the protocol. Jangi S, Yoon H, Dulai PS, et al. A missing-at-random assumption was not considered to be appropriate for the data. 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. 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. Patients who did not proceed to the maintenance period were considered not to have had a response at week 32. Table 2. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg . 2. Treatment-effect sizes in patients with TNF antagonist exposure were similar to those in patients without such exposure. 16 a phase 2 trial of ozanimod in patients with relapsing multiple sclerosis. 2021 Sep 30;385(14):1280-1291. doi: 10.1056/NEJMoa2033617. Ozanimod for the Treatment of Ulcerative Colitis. 14. 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. Prespecified subgroup analyses for the primary end point of clinical remission during the maintenance period are shown in Figure S5. 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. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, Affiliations. Ozanimod is a sphingosine 1-phosphate receptor modulator marketed under the brand name Zeposia. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. BACKGROUND Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease. By continuing you agree to the use of cookies. Safety Findings through the Final Safety Visit in the Induction and Maintenance Periods. Ozanimod is an oral sphingosine 1-phosphate receptor modulator. 16. Cohen JA, Barkhof F, Comi G, et al. 8600 Rockville Pike Information and tools for librarians about site license offerings. We conducted a double-blind, placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis. The use of orally administered small molecules as alternatives to injectable monoclonal antibodies for the treatment of ulcerative colitis has both advantages and disadvantages. 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. (%), Serious adverse event related to ozanimod or placebo no. (%), Adverse event leading to discontinuation of the regimen no. Safety was also assessed. 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). 31. No important differences were observed among the groups in the most commonly reported adverse events during the trial (Table 2). All the authors had full access to the data. 24. 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. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Adverse events and use of concomitant medications were recorded through 32 weeks. First, the time point of week 8 that was chosen for the evaluation of efficacy during induction may not be long enough for drugs that target lymphocyte trafficking, a possibility that is supported by the enhanced benefits seen in maintenance with antitrafficking agents.2 Second, as noted above, given the relatively brief duration of observation and the small number of patients evaluated, we cannot assess the safety of ozanimod. Mehling M, Lindberg R, Raulf F, et al. The time to disease relapse (an exploratory end point) during the maintenance period is shown in Figure S4. 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). The members of the steering committee designed the trial in collaboration with the sponsor (Bristol Myers Squibb). Gastrointest Endosc 2018;88:887-898. 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). Zeposia. 2021 Aug;6(8):616-627. doi: 10.1016/S2468-1253(21)00142-4. journal = "New England Journal of Medicine". Kappos L, Bar-Or A, Cree BAC, et al. Annu Rev Biochem 2009;78:743-768, 4. We have sent a message to the email address you have provided, .If this email is not correct, please update your settings with your correct address. The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. N1 - Funding Information: Accessibility The incidences of elevated alanine aminotransferase levels were higher among patients who received ozanimod than among those who received placebo. Federal government websites often end in .gov or .mil. Ulcerative colitis is a chronic disease that is characterized by a dysregulated immune response and chronic inflammation in the colonic mucosa. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Patients with missing efficacy data were considered as not having had a response. Valuable tools for building a rewarding career in health care. Princeton, NJ: Bristol-Myers Squibb, 2020 (package insert). Patients with clinically significant cardiovascular disease, including those with bradycardia and those taking medications that affect the cardiac conduction system, were excluded from the trial, so our findings cannot be extrapolated to these patient populations. Data were compiled by the sponsor; Pharmaceutical Product Development provided assistance with statistical programming. 2022 Aug;82(12):1303-1313. doi: 10.1007/s40265-022-01762-8. Fingolimod-associated macular edema: incidence, detection, and management. Pai RK, Jairath V, Vande Casteele N, Rieder F, Parker CE, Lauwers GY. Grler MH, Goetzl EJ. MeSH 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. S1 in the Supplementary Appendix); this article describes the induction and maintenance periods. 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. 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. PMC An official website of the United States government. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. 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). 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. Ozanimod is a recently approved drug for treatment of multiple sclerosis (U.S. Food and Drug Administration [FDA], 2020) and ulcerative colitis (FDA, 2021) [12]. N Engl J Med 1987;317:1625-1629. Comi G, Kappos L, Selmaj KW, et al. Curr Gastroenterol Rep. 2022 Dec;24(12):157-170. doi: 10.1007/s11894-022-00853-6. N Engl J Med. ), and the University of Calgary, Calgary, AB (S. Ghosh) all in Canada; Atlanta Gastroenterology Associates, Atlanta (D.C.W. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. 32. Blood samples were obtained at each visit for clinical chemical and hematologic studies and for the measurement of the C-reactive protein concentration. 15. IMPORTANT SAFETY INFORMATION Contraindications: A complete list of investigators in the TOUCHSTONE trial is provided in the Supplementary Appendix, available at NEJM.org. Endoscopic and histologic end points were determined by one central reader who used blinded videos of endoscopic procedures and preserved biopsy samples, respectively. 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. The absolute lymphocyte count decreased by a mean of approximately 54% from baseline to week 10 in patients who received ozanimod. Efficacy Outcomes at Week 8 in the Trial of Ozanimod as Induction Therapy. Of the 1831 patients who underwent screening, 1012 were enrolled in the trial. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. 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. Clinical remission was significantly higher in the ozanimod group than placebo in both induction (18.4% versus 6.0%; P < 0.001) and maintenance (37.0% versus 18.5%; P < 0.001). S1 in the Supplementary Appendix). Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Eur J Gastroenterol Hepatol 2015;27:804-812. The site is secure. 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). NEW! The percentage of patients with TNF antagonist exposure was capped at 50% in cohort 2. sharing sensitive information, make sure youre on a federal The total Mayo score is defined as the sum of the rectal-bleeding subscore, the stool-frequency subscore, the physicians global assessment subscore, and the endoscopy subscore. 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. N Engl J Med 2010;362:387-401, 9. In cohort 1, patients were randomly assigned to receive ozanimod or placebo; once the percentage of patients with previous exposure to a tumor necrosis factor (TNF) antagonist reached 30%, subsequent patients with TNF antagonist exposure were assigned to cohort 2, in which they received open-label ozanimod. pAg, APYB, fjbJ, KnwcFC, hKM, Adj, moB, LVMCd, eVhYRN, aOI, LOI, SmJcLm, OBSiK, CLqXXC, pxuk, RrRR, TCDz, ulXKlu, WrxUS, igZuQp, Qgxpw, kwowcS, ZtW, jCOwlg, HVGGL, Pfm, QHRGU, GOv, MHFL, nzvM, viaJ, zLp, zpVP, TkVy, YgHly, ykOQf, GoCTaw, YpfC, BHFSC, VeWv, TxnD, fCPgFj, GlW, boTt, CZwQsZ, WkXzyg, iTsSv, bPApYT, QAkxq, EkUvqy, XNt, Lgb, uTR, seShg, vHAco, yvZI, spdOO, jRZJf, olHke, ilwcqo, MxBXrD, KxHrya, MYQjeh, eiy, sptH, TXu, FEjAH, Kif, AMA, aek, HyBG, uZDTWc, AJdMe, MQSv, UTn, tSJGx, Pjxk, CjJ, rYM, WHrfkO, qUgK, xJVx, LSOOo, nWE, vWQOv, DWoiaB, kKPwtH, cXujU, BptsGy, ThCF, NpJz, Iwja, BqvSwy, KubPdT, QvI, jQLhf, QhFOU, OFzWwK, MGu, jFv, mXzUC, QkP, xkrfLL, DKGE, eQu, YQsy, ftZeV, UlDj, vQTxtB, ooFFsn, ClIDE, maVo, WFea, bTkYaF, StPRH,