The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Point [GPP]) are defined at the end of the "Major Recommendations" field.
There is consistent evidence from several class I studies and meta-analyses for a beneficial effect of glucocorticoid treatment in relapses of multiple sclerosis (MS). Hence, treatment with intravenous (IV) or oral methylprednisolone in a dose of at least 500 mg daily for 5 days should be considered for treatment of relapses (level A recommendation). Treatment with IV methylprednisolone (1 g once daily for 3 days) should be considered as an alternative treatment (good practice point; Rieckmann et al., 2004). Treatment with IV methylprednisolone (1 g once daily for 3 days with an oral tapering dose) may be considered for treatment of acute optic neuritis (level B recommendation).
There is no evidence of major differences in the efficacy of methylprednisolone treatment given IV or orally in terms of clinical efficacy or side-effects, but prolonged, oral treatment may possibly be associated with a higher prevalence of side-effects. Furthermore, because of the low number of patients included in the available clinical trials, some efficacy differences between the IV and oral route of administration cannot be excluded. The optimal dosage, the specific glucocorticoid to be used, and whether to use a taper after initial pulse therapy have not been adequately addressed in randomized, controlled trials. This implies a need for new, randomized studies assessing risk/benefit ratios and adverse effects of specific glucocorticoids, dose, and route of administration for treatment of MS relapses.
There is insufficient data to clearly define patient subgroups who are more likely to respond to methylprednisolone treatment, but treatment may be more efficacious in patients with clinical, magnetic resonance imaging (MRI), or cerebrospinal fluid (CSF) evidence (increased myelin basic protein [MBP] concentration in CSF) indicating higher disease activity (level C recommendation). Administration of treatment in an inpatient or outpatient setting has not been addressed in clinical trials, but consideration could be given to administering the first course of methylprednisolone as an inpatient (good practice point).
In patients who fail to respond to therapy with methylprednisolone in the dose range used in the randomized, placebo-controlled trials, treatment with higher doses (up to 2 g daily for 5 days) should be considered (level C recommendation; Rieckmann et al., 2004).
Patients with inflammatory demyelination, including patients with MS, who have not responded to treatment with methylprednisolone may benefit from plasma exchange treatment, but only about one-third of treated patients are likely to respond. This treatment regimen should probably be restricted to a subgroup of patients with severe relapses (level B recommendation). A randomized, controlled study specifically addressing the effect of plasma exchange in patients with severe relapses of MS not responding to methylprednisolone treatment would be desirable.
A more intense, interdisciplinary rehabilitation programme should be considered after treatment with IV methylprednisolone as evidence from a single trial suggests that this probably further improves recovery (level B recommendation).
There is insufficient data to support the use of intravenous immunoglobulin (IVIG) therapy as monotherapy for relapses of MS. Treatment with intravenous immunoglobulin as an add-on to treatment of MS relapses with methylprednisolone or as monotherapy for acute optic neuritis is not efficacious (level A recommendation). Neither is natalizumab as monotherapy efficacious in MS relapses.
Definitions:
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good practice point: For insufficient evidence to support firm recommendations, the term 'Good practice point' was used.
