IV Methylprednisolone (IVMP)
The pivotal Optic Neuritis Treatment Trial (ONTT) demonstrated the efficacy of IVMP 1 g/day for 3 days in acute optic neuritis, thus laying the foundation for the treatment of MS exacerbations (Beck et al., 1992). IVMP for 3 days was also shown to significantly delay the development of MS within the first two years.
High Dose Oral Prednisone
A 1250 mg dose of oral prednisone has a bioavailability equal to 1 g IVMP (Morrow et al, 2004). Although studies since the ONTT have found high dose oral prednisone and IVMP to be equally effective in managing relapses, most neurologists continue to favor a 3-5 day course of IVMP, with or without an oral prednisone taper (Thrower, 2009). However, the lower cost of oral prednisone may be a consideration.
Intramuscular adrenocorticotrophic hormone (ACTH)
ACTH is FDA-approved and available as a second-line option for patients who have poor venous access or prefer the convenience of a self-injection. It has been shown to have direct anti-inflammatory and immunomodulatory effects via activation of central and peripheral melanocortin receptors, as well as effects achieved by systems originating in the adrenal cland. Although ACTH has been shown to be as effective as IVMP in managing relapses (Arnason et al, 2013; Thompson et al., 1989; Milanese et al., 1989; Barnes et al., 1985), it is prescribed much less often because of its high cost.
In 2011, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) recommended plasmapheresis as a second-line treatment for steroid-resistant exacerbations in relapsing forms of MS (Cortese et al., 2011).
Intravenous Immunoglobulin (IVIG)
IVIG may be considered for relapses during pregnancy (during which time steroids should be avoided if possible), and it may reduce the risk of post partum relapses (Hellwig et al., 2009; Achiron et al., 2004). IVIG is sometimes used to treat relapses that don’t respond to corticosteroids (Thrower, 2009), although the supportive evidence is limited.
During pregnancy, relapses severe enough to warrant treatment can be safely managed with a short course of corticosteroids after the first trimester. Methylprednisolone is the preferred drug because it is metabolized before crossing the placenta (Ferrero et al., 2004). IVIG is safe for use during pregnancy and may provide some benefit (Ferrero et al., 2004).