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Neurological conditions
Published in David M. Luesley, Mark D. Kilby, Obstetrics & Gynaecology, 2016
Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. This drug should be discontinued at least 2 months before conception due to a presumed teratogenic risk shown in animals.
Disorders of vision in multiple sclerosis
Published in Clinical and Experimental Optometry, 2022
Roshan Dhanapalaratnam, Maria Markoulli, Arun V Krishnan
Fingolimod was the first oral disease-modifying agent used in multiple sclerosis and remains one of the most widely used oral agents for multiple sclerosis. It is a sphingosine 1-phosphate receptor modulator, and limits the lymphocyte egress from lymph nodes, and subsequently reduces the degree of lymphocyte infiltration into the CNS and thereby inflammatory exacerbations of multiple sclerosis.91 Fingolimod is known to cause macular oedema at a rate of 0.5% of patients on the drug.92 For this reason, it is recommended that OCT is performed prior to initiating fingolimod and is repeated at three months following commencement of treatment. If detected, macular oedema tends to resolve with cessation of the drug. The risk of macular oedema is increased in those with diabetes or uveitis.
Understanding and managing autonomic dysfunction in persons with multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2021
Ivan Adamec, Magdalena Krbot Skorić, Mario Habek
Drugs that are used in treatment of MS may as well cause cardiovascular AD. Treatment of MS relapses with pulse corticosteroid therapy has been linked to occurrence of atrial fibrillation [35]. Some of the disease modifying therapies in MS, such as sphingosine 1-phosphate receptor modulators, are known to alter cardiovascular autonomic function. One example is fingolimod where treatment initiation must be accompanied with cardiac monitoring since sinus bradycardia may occur following its administration [36]. Hilz et al. demonstrated that fingolimod dampens autonomic modulation at the cardiac level which is the proposed mechanism for bradycardia development [37]. Similar effects on cardiovascular autonomic function have been noted with the use of siponimod, a more selective sphingosine 1-phosphate receptor modulator. After treatment initiation in a group of 26 pwMS a statistically significant decrease in heart rate and elevation of systolic blood pressure occurred where changes in heart rate variability were a predictor of heart rate decrease [38].
The importance of considering differences in study and patient characteristics before undertaking indirect treatment comparisons: a case study of siponimod for secondary progressive multiple sclerosis
Published in Current Medical Research and Opinion, 2020
Imtiaz A. Samjoo, Evelyn Worthington, Anja Haltner, Chris Cameron, Richard Nicholas, Frank Dahlke, Nicholas Adlard
Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system that results in irreversible morbidity12. For the majority of patients with MS – approximately 85%13 – the clinical course begins with relapsing-remitting MS (RRMS). Each decade that a patient lives with RRMS is associated with an increase in the risk of conversion to secondary progressive MS (SPMS), in which irreversible disease progression follows the initial course of the relapsing-remitting disease, with or without superimposed relapses. Several disease-modifying treatments (DMTs) are currently available for RMS and/or RRMS, although approval and licensing varies by jurisdiction. Overall, these include interferon beta-1a (IFN β-1a), interferon beta-1b (IFN β-1b), glatiramer acetate, teriflunomide, fingolimod, cladribine, dimethyl fumarate, alemtuzumab, mitoxantrone, ocrelizumab, and natalizumab. However, therapies shown to be effective in reducing relapses in RRMS have not demonstrated substantial evidence of therapeutic effect in progressive forms of MS, such as SPMS, particularly with respect to delaying or preventing the progression of disability14. As such, there remains an unmet need for adequate treatment and prevention of disability progression in patients with SPMS14. Siponimod is a sphingosine-1-phosphate receptor modulator that was recently evaluated in the pivotal phase 3 trial EXPAND15, and demonstrated significant reduction in disability progression and frequency of relapse in a current and advanced SPMS population14.