Efficacy of Prednisone in the Treatment of Ocular Myasthenia The EPITOME Study
This is a randomized, double-blind, placebo-controlled trial. Participants with recent-onset ocular myasthenia will initially be treated with pyridostigmine alone. Participants who do not attain minimal manifestation status (MMS), defined by the Myasthenia Gravis Foundation of america (MGFa) post-intervention status classification scheme, within the first month of therapy will be randomized 1:1 to receive either prednisone or matching placebo. Subjects in both groups will remain on a stable dose of pyridostigmine. The primary outcome variable is treatment failure, defined as a failure to achieve MMS that is sustained over two consecutive in-person study visits within four months of randomization, toxicity leading to discontinuation of study drug or progression to GMG. Prednisone will be started at a dosage of 10mg every other day, with the dosage titrated every two weeks according to whether or not MMS has been attained and the presence or absence of adverse events. While on prednisone, participants will be followed monthly for a total of 4 months. Telephone evaluations will occur mid-way between all study visits during any period of dosage adjustment. The purpose of the telephone evaluations is to evaluate myasthenic symptoms, to inquire about adverse events and to make adjustments to the prednisone dosage, if necessary.
From Protocol Page 20
1.Weakness confined to the extra-ocular muscles, eyelid levator and eye closure with an ocular-QMG1 score >= 1
2.At least one of the following combinations of abnormal diagnostic testing: (a) Elevated acetylcholine receptor antibody titers, (b) Abnormal repetitive nerve stimulation (> 10% decrement following slow repetitive nerve stimulation) of any nerve-muscle pair, (c) Abnormal jitter on single fiber or concentric needle electromyography in any muscle, (d) Positive ice test and brain MRI that demonstrates no central nervous system pathology that mimics ocular myasthenia, or (e) Positive Tensilon test and brain MRI that demonstrate no central nervous system pathology that mimics ocular myasthenia
3.Either no prior treatment or participant has persistent ocular symptoms that are functionally limiting or troublesome despite treatment with pyridostigmine.
4.Age 18 years or older, male or female
5.Capable of providing informed consent and complying with study procedures
6.Identifiable primary care physician to assist with management of medical complications that may arise as a consequence of steroid therapy
7.Willing to be randomized to a trial of prednisone or placebo if symptoms respond inadequately to pyridostigmine.