Assistant Professor of Neurology, Weill Cornell Medical College
Dr. Perumal reports she is a consultant for Genzyme and Biogen.
SYNOPSIS: Based on outcomes measured at one and six months following optic neuritis in the context of multiple sclerosis, these investigators reported similar efficacy when comparing oral to bioequivalent doses of intravenous steroids.
SOURCE: Morrow SA, Fraser JA, Day C, et al. Effect of treating acute optic neuritis with bioequivalent oral vs intravenous corticosteroids: A randomized clinical trial. JAMA Neurol 2018;75:690-696.
A three- to five-day course of intravenous (IV), high-dose corticosteroids is the standard practice for the treatment of optic neuritis. The benefits of this treatment were well established by the Optic Neuritis Treatment Trial (ONTT), in which three days of 1,000 mg of methylprednisolone IV was compared to oral prednisone 1 mg/kg/day for 14 days and placebo.1 The IV therapy was superior in rate of recovery, and there were greater numbers of cases of recurrent optic neuritis in the oral prednisone group when compared to both the IV and placebo arm. However, the oral dose was not bioequivalent to the IV dose. Since the publication of the ONTT study, some groups have examined bioequivalent doses of oral vs. IV steroids for the treatment of relapses of multiple sclerosis and found them to have similar efficacy. Morrow et al examined the recovery of vision following an episode of acute optic neuritis in patients treated with bioequivalent doses of oral and IV steroids, respectively.
In this single-blind, randomized study at a tertiary care center, patients with multiple sclerosis/clinically isolated syndrome who developed acute optic neuritis were randomized to receive either 1,000 mg of IV methylprednisolone or an oral bioequivalent dose of 1,250 mg of prednisone for three days. The optic neuritis had to be unilateral and there had to be no history of prior optic neuritis in that eye. The assessors were blinded throughout the study. Assessments were done at baseline and at one and six months. The primary outcome was the P100 latency on VEP at six months. Secondary outcomes were P100 at one month and the best corrected visual acuity (BCVA) assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and low-contrast BCVA with Sloan letter charts at one and six months.
Participants were enrolled between March 2012 and May 2015 at a single tertiary care center. Based on a power analysis, 55 patients were randomized for the trial, and, at the time of final analysis, 22 patients were in the oral steroid group and 23 were in the IV steroid group. The mean age was 34.6 years and 62.2% were women. The median baseline BCVA was 20/100 (range 20/40 to NLP). The mean P100 on VEP was 191.0 milliseconds. At the six-month assessment of P100, which was the primary outcome, P100 in the IV group decreased from 181.9 to 119.0 milliseconds, and P100 in the oral group decreased from 200.5 to 133.8. The improvement was not statistically significantly different between the two groups. Similarly, there was no statistical difference between the two groups at one month P100 on VEP. The improvement in BCVA on ETDRS chart and BCVA on low-contrast chart also was not statistically different at either one month or six months between the two groups.
The most commonly reported adverse events, gastrointestinal distress, insomnia, and fatigue, were similar in the two groups and not significantly different. The limitations of this study are the relatively small numbers of patients (because it was a single-center study) and likely recruitment bias (because physicians may not have referred patients they thought were too severely affected to be in the study). Also, the initial outcome was measured at one month; hence, the rapid onset of improvement was not assessed. But despite these limitations, the investigators demonstrated comparable efficacy of oral and IV steroids in subjective and objective measures.
Bioequivalent doses of oral steroids seem to have similar efficacy compared to IV steroids on outcomes measured at one and six months following an episode of acute optic neuritis in the context of multiple sclerosis. The outcomes assessed were BCVA and P100 latency on VEP, which included clinical and objective measures. Oral corticosteroids should be considered as an option or alternative to IV steroids in the treatment of acute optic neuritis, especially when patient convenience, feasibility/accessibility to infusions, and costs are considered. There are dramatic differences in costs between oral and IV medications, as well as huge differences in administration costs, all in favor of oral treatment.
- Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med 1992;326:581-588.