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Oral versus intravenous corticosteroids in acute relapses of multiple sclerosis

1997; Elsevier BV; Volume: 349; Issue: 9066 Linguagem: Inglês

10.1016/s0140-6736(97)26023-x

1474-547X

Jacques De Keyser, Cornelius Zwanikken,

Polyomavirus and related diseases

There is no reason why an intravenous (iv) rather than oral course of corticosteroids should be better for the treatment of relapses in multiple sclerosis, provided that comparable bioavailability is obtained. The common practice of the use of high iv doses (500–1000 mg) of methylprednisolone is based on the results of two placebo-controlled studies showing that after 1 week, 85–92% of those who received active treatment had improved, by contrast with 33–40% of those who received placebo.1Durelli L Cocito A Riccio A et al.Highdose intravenous methylprednisolone in the treatment of multiple sclerosis. Clinical-immunologic correlations.Neurology. 1985; 36: 238-243Crossref Google Scholar, 2Milligan NG Newcombe R Compston DAS A double-blind controlled trial of high-dose methylprednisolone in patients with multiple sclerosis. 1: clinical effects.J Neurol Neurosurg Psychiatry. 1986; 50: 511-516Crossref Scopus (333) Google Scholar Oral treatment with 500 mg methylprednisolone daily gave similar results.3Alam SM Kyriakides T Lawden M Newman PK Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high-dose.J Neurol Neurosurg Psychiatry. 1993; 56: 1219-1220Crossref PubMed Scopus (139) Google Scholar Barnes and colleagues' claim (March 29, p 902)4Barnes D Hughes RAC Morris RW et al.Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.Lancet. 1997; 349: 902-906Summary Full Text Full Text PDF PubMed Scopus (192) Google Scholar that lower conventional doses of oral methylprednisolone (48 mg per day) and high-dose iv methylprednisolone are therapeutically equivalent for the treatment of multiple sclerosis relapses is in contradiction to other findings. In their accompanying commentary Barkhof and Polman5Barkhof F Polman C Oral or intravenous methylprednisolone for acute relapses of multiple sclerosis.Lancet. 1997; 349: 893-894Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar (p 893) correctly state that the reduction in disability in the high-dose iv methylprednisolone group was unusually small (0–0·5 expanded disability status scale [EDSS] points) compared with previous studies (1·5–2·0 EDSS points). The 3-day course with iv methylprednisolone might well have been too short to produce a beneficial effect. Patients often only start to improve after 3 days, and in all previous controlled studies, including the previous one of Barnes et al, iv methylprednisolone was given for at least 5 days.1Durelli L Cocito A Riccio A et al.Highdose intravenous methylprednisolone in the treatment of multiple sclerosis. Clinical-immunologic correlations.Neurology. 1985; 36: 238-243Crossref Google Scholar, 2Milligan NG Newcombe R Compston DAS A double-blind controlled trial of high-dose methylprednisolone in patients with multiple sclerosis. 1: clinical effects.J Neurol Neurosurg Psychiatry. 1986; 50: 511-516Crossref Scopus (333) Google Scholar, 3Alam SM Kyriakides T Lawden M Newman PK Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high-dose.J Neurol Neurosurg Psychiatry. 1993; 56: 1219-1220Crossref PubMed Scopus (139) Google Scholar In addition, in Barnes and colleagues' Lancet report, it is unclear how many patients in each group improved (responders), which is clinically more relevant than comparing changes in median EDSS. We currently treat relapses in multiple sclerosis for 5 days with 16 mg oral dexamethasone daily. This dosage produces a bioavailability similar to an iv course of dexamethasone (8 mg), which gave a response rate equivalent to high-dose iv methylprednisolone. Before adapting this practice we had studied the effect of this oral regimen in an open-label setting in 25 patients with multiple sclerosis (18 female and seven male, mean age 40 [SD 10] years, mean EDSS 5·3 [1·5]) who presented with a relapse of less than 2 weeks' duration. At 7 days the EDSS had improved by one or more grades (responders) in 88% (22 patients), and after 4 weeks in 92% (23 patients). Side-effects were minimum, and included insomnia (two), facial oedema and redness (five), palpitations (one), acne (one), and epigastric discomfort (two). The main advantage of the oral administration of corticosteroids is that patients with a relapse can be treated at home. Because Barnes and colleagues have compared two forms of treatment that may both be ineffective, there is no reason to advocate a course with conventional low doses of methylprednisolone for 3 weeks, with the risk of running into chronic treatment. A 5-day oral course with 500 mg methylprednisolone or 16 mg dexamethasone per day is safe and works well. If there is little or no response, patients can still be admitted for an additional 5-day iv course. Oral versus intravenous corticosteroids in acute relapses of multiple sclerosisAuthors' reply Full-Text PDF