Multiple sclerosis Basic Management

Multiple Sclerosis, an immune-mediated CNS disease, has no cure but treatments delay progression. Relapsing-remitting MS is managed with oral, infusion, and injection therapies. Secondary progressive MS involves switching treatments, with options like siponimod. Primary progressive MS is treated with ocrelizumab, especially in younger patients. Acute attacks are managed with high-dose methylprednisolone.

2024-01-06 05:35:51 - Editor

Multiple sclerosis (MS) is an immune mediated demyelinating disease of the central nervous system (CNS). It has three subtypes which are relapsing remitting, secondary progressive and primary progressive. No cure is available for MS, with a lot of agents which are effective to delay progression of the disease. Early treatment is advisable as it is associated with later relapses and slower disease progression. Treatment mostly continues indefinitely once been effective. (1, 2)

Management of relapsing remitting MS (RRMS):

Disease modifying therapies (DMT) are the main treatment for RRMS. DMT include three subclasses which are; A- Oral agents, such as, dimethyl fumarate (the starting dose is 120 mg twice daily. After 7 days, the dose should be increased to 240 mg twice daily), teriflunomide (14 mg daily), monomethyl fumarate (starting at 95 mg twice daily for 7 days and then increase to maintenance dose of 190 mg twice daily), fingolimod (0.5 mg daily), siponimod ( starting at 0.25 mg daily on days 1 and 2, followed by 0.5 mg daily on day 3, 0.75 mg daily on day 4, and 1.25 mg daily on day 5, to reach the maintenance dose of 2mg daily from day 6 provided that patients do not have CYP2C9*2*3 or *1*3 genotype), ozanimod (starting at 0.23 mg daily on days 1- 4, then, titrate to 0.46 mg daily on days 5-7, then escalate to 0.92 mg daily from day 8) and cladribine (at a cumulative dosage of 3.5 mg/kg divided into two yearly treatment courses (1.75 mg/kg per treatment course to be given every 6 months. Each treatment course is divided into two treatment cycles of four or five days separated by approximately four weeks). (3, 4, 5, 6) B- Infusion therapy, such as, natalizumab (300 mg intravenous (IV) infusion every four weeks), ocrelizumab at an initial dose of 300 mg IV infusion, followed by a second 300 mg IV infusion two weeks later. Six months later, it is given at 600 mg IV infusion every six months and alemtuzumab (12 mg daily for five consecutive days then 12 mg daily for three consecutive days 12 months later). (7, 8, 9) C- Injection therapies, such as, interferon beta-1a (30 mcg intramuscular injection once a week) , interferon beta-1B at 0.25 mg every other day subcutaneously, and glatiramer (Either 20 mg daily or 40 mg three times a week by subcutaneous injection). (10, 11, 12) Some patients with RRMS may have disease activity which is refractory to initial DMT. Then, it is advisable to switch to another class of DMT. Other options for patients who are poor responders to all first line DMT include intravenous pulsy methylprednisolone at 1000 mg monthly, intravenous immune globulin or other infusion therapies including rituximab (2 infusions of 1000 mg (two weeks apart) every six months, or more recently 1000 mg IV initial dose, followed by 500 mg IV every six months for 2 years), ofatumumab ( starting with 20 mg administered subcutaneous at weeks zero, one, and two. Then from week 4, 20 mg monthly), or azathioprine up to 3 mg/kg per day. (13, 14, 15, 16) Hematopoietic stem cell transplantation is being evaluated for refractory disease. (16)

Management of secondary progressive MS (SPMS):

For patients who develop SPMS and have an active disease, it is advisable to discontinue the disease modifying therapy (DMT) used during RRMS and switching to another class of DMT especially Siponimod (starting at 0.25 mg daily on days 1 and 2, followed by once-daily doses of 0.5 mg on day 3, 0.75 mg on day 4, and 1.25 mg on day 5, to reach the patient's prescribed maintenance dose from day 6) which is effective for reducing progression in SPMS as per trial results. (17) Other agents include ocrelizumab (an initial dose of 300 mg IV, followed by a second dose of 300mg two weeks later. Then after 6months, ocrelizumab is given as 600 mg IV infusion every six months), Rituxumab (2 infusions of 1000 mg (two weeks apart) every six months, or more recently 1000 mg IV initial dose, followed by 500 mg IV every six months for 2 years). (18, 19, 20) For patients with SPMS and low level of active disease, it is reasonable to continue the current DMT or switching to siponimod, provided that it modestly reduced the risk of disability progression in patients with SPMS as per trial results. (19) For patients with inactive SPMS (no ongoing relapses or MRI lesions of the brain and spinal cord) who have been nonambulatory for at least two years, it is reasonable to discuss stopping DMT. (19) For patients with suboptimal response or refractory disease, it was suggested to try cladribine (at a cumulative dosage of 3.5 mg/kg divided into two yearly treatment courses (1.75 mg/kg per treatment course to be given every 6 months. Each treatment course is divided into two treatment cycles of four or five days separated by approximately four weeks). Also, methylprednisolone at 1000 mg alone or in combination with other immunomodulatory agents including azathioprine (titrated up to a dose of 2 mg/kg per day). Finally, stem cell transplant may be effective in refractory SPMS. (21, 22, 23)

Management of primary progressive MS (PPMS):

For patients with PPMS, disease modifying therapy (DMT) is advisable with ocrelizumab for young patients (< 55 years). For patients who are older, symptomatic therapy may be most appropriate. Also, ocrelizumab could be tried without proven efficacy. (24, 25) The initial dose of ocrelizumab is 300 mg IV infusion, followed two weeks later by a second 300 mg IV infusion. Subsequently, ocrelizumab is given as 600 mg IV infusion every six months. (25) Other agents include bolus intravenous methylprednisolone 1000 mg either alone or in combination with other immunomodulatory agents including methotrexate 7.5- 20 mg per week subcutaneous, Intravenous immune globulin (IVIG) . Other agents which could be tried but without any proven efficacy include glatiramer or interferon beta 1b. (26, 27, 28)

Management of acute attacks of MS:

They are typically treated with pulsy doses of methylprednisolone (1gm/day). (29)

References

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