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3 results on '"Sphingosine 1 Phosphate Receptor Modulators"'

1. Differential effects of selective versus unselective sphingosine 1-phosphate receptor modulators on T- and B-cell response to SARS-CoV-2 vaccination.

Author

Proschmann U, Mueller-Enz M, Woopen C, Katoul Al Rahbani G, Haase R, Dillenseger A, Dunsche M, Atta Y, Ziemssen T, and Akgün K

Subjects
Humans, COVID-19 Vaccines, SARS-CoV-2, Sphingosine-1-Phosphate Receptors, Longitudinal Studies, Antibodies, Viral, Vaccination, Sphingosine 1 Phosphate Receptor Modulators, COVID-19 prevention & control, Multiple Sclerosis
Abstract

Background: Sphingosine 1-phosphat receptor modulators (S1PRMs) have been linked to attenuated immune response to SARS-CoV-2 vaccines., Objective: To characterize differences in the immune response to SARS-CoV-2 vaccines in patients on selective versus unselective S1PRMs., Methods: Monocentric, longitudinal study on people with multiple sclerosis (pwMS) on fingolimod (FTY), siponimod (SIP), ozanimod (OZA), or without disease-modifying therapy (DMT) following primary and booster SARS-CoV-2 vaccination. Anti-SARS-CoV-2 antibodies and T-cell response was measured with electro-chemiluminescent immunoassay and interferon-γ release assay., Results: Primary vaccination induced a significant antibody response in pwMS without DMT while S1PRM patients exhibited reduced antibody titers. The lowest antibodies were found in patients on FTY, whereas patients on OZA and SIP presented significantly higher levels. Booster vaccinations induced increased antibody levels in untreated patients and comparable titers in patients on OZA and SIP, but no increase in FTY-treated patients. While untreated pwMS developed a T-cell response, patients on S1PRMs presented a diminished/absent response. Patients undergoing SARS-CoV-2 vaccination before onset of S1PRMs presented a preserved, although attenuated humoral response, while T-cellular response was blunted., Conclusion: Our data confirm differential effects of selective versus unselective S1PRMs on T- and B-cell response to SARS-CoV-2 vaccination and suggest association with S1PRM selectivity rather than lymphocyte redistribution., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: U.P. received speaker fee from Merck, Biogen, Bayer, and Roche and personal compensation from Biogen, Roche, and Sanofi for consulting service. C.W. received travel support from Novartis. A.D. received personal compensation and travel grants from Sanofi-Aventis, Janssen-Cilag, Biogen, Celgene/Bristol-Myers Squibb, and Roche for speaker activity. T.Z. reports consulting or serving on speaker bureaus for Biogen, Celgene, Roche, Novartis, Celgene Merck, and Sanofi as well as research support from Biogen, Novartis, Merck, and Sanofi. K.A. received personal compensation from Roche, Sanofi, Alexion, Teva, Biogen, and Celgene for consulting service. M.M.-E., G.K.A.R., R.H., M.D., and Y.A. have nothing to disclose.

Published
2023
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2. Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis

Author

Shubha Bhat, Alyssa P. Stewart, and David Choi

Subjects
Sphingosine 1 Phosphate Receptor Modulators, Ozanimod, Oxadiazoles, business.industry, Pharmacology, medicine.disease, Inflammatory bowel disease, Sphingosine 1-phosphate Receptor Modulator, Ulcerative colitis, chemistry.chemical_compound, Clinical Trials, Phase III as Topic, chemistry, Indans, Humans, Immunologic Factors, Medicine, Colitis, Ulcerative, Pharmacology (medical), Sphingosine-1-phosphate, business
Abstract

Objective To review the pharmacological and clinical profile of ozanimod in the treatment of ulcerative colitis (UC). Data Sources A PubMed search was conducted from inception to July 2021 using the keywords ozanimod, ulcerative colitis, and sphingosine 1-phosphate receptor modulator. Information was also extracted from published abstracts and the package insert. Study Selection and Data Extraction Phase 2 and 3 studies and relevant literature on ozanimod pharmacological and clinical profiles were reviewed. Data Synthesis Ozanimod approval was based on True North, a phase 3 trial evaluating ozanimod’s efficacy and safety in the treatment of moderate to severe UC. Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. Common adverse events included infections, headaches, hypertension, bradycardia, and liver enzyme elevations. Relevance to Patient Care and Clinical Practice Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications. However, its safety profile is unique, requiring extensive assessments prior to initiation of and during treatment. Thus, it is unclear how ozanimod will be positioned in UC treatment. Conclusion Ozanimod is another option in the growing arsenal of UC treatment. Although it offers a novel mechanism of action and is administered orally, there are important safety, dosing, and pharmacokinetic factors to consider prior to initiation and use.

Published
2021

3. Not all side effects are unwelcome …

Author

Daniel Waldvogel, Borbala Keserü, and Max Wiederkehr

Subjects
Adult, Sphingosine 1 Phosphate Receptor Modulators, medicine.medical_specialty, Multiple Sclerosis, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, MEDLINE, Insect Bites and Stings, medicine.disease, Dermatology, Neurology, medicine, Humans, Neurology (clinical), business
Published
2019

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