Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): A randomized, controlled trial

Abstract

Introduction: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine.

Methods: This investigation was a randomized, double-blind, placebo-controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure.

Results: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double-blind therapy. Treatment failure incidence was 100% (95% CI 48%-100%) in the placebo group (n = 5) vs. 17% (95% CI 0%-64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups.

Conclusions: A strategy of low-dose prednisone with gradual escalation appears to be safe, well-tolerated, and effective in treating OMG.

Keywords: clinical trial; neuromuscular; ocular myasthenia; prednisone; steroids.

Figure 1. Study Schema

Following enrollment (Week -4), study participants were treated with escalating doses of pyridostigmine for a period of 4 weeks. Those who did not achieve MMS were randomized to receive prednisone or placebo in a double-blind manner (Stage 1). Outcomes were assessed at Week 16, following which those participants who had not yet achieved MMS were crossed over to receive open-label high-dose prednisone (Stage 2). MMS – minimal manifestation status; OL – open label; DB – double-blind. indicates in-person visit; indicates telephone visit.

Figure 2. Participant Flow for Double-Blind Phase

Of the 145 patients assessed for eligibility, 11 were randomized, and 10 received study drug. No participants were lost to follow-up, and all 11 participants were included in the primary analysis.

Figure 3. Secondary Outcome Measures

A. Ocular QMG scores at each time point between randomization (Week 0) and the end of the double-blind phase of the trial (Week 16); scores range from 0 (normal) to a maximum of 15. B. MG-QoL-15 scores at randomization and Week 16; scores range from 0 (normal) to a maximum of 60. C. NEI-VFQ-25 scores at randomization and Week 16; scores range from 0 to 100 (normal). D. NEI-VFQ-25 10-item neuro-ophthalmological supplement scores at randomization and Week 16; scores range from 0 to 100 (normal).