Alternate Day Steroids for Polymyositis
Alternate Day Steroids for Polymyositis
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: An alternate-day steroid protocol appears to be just as efficacious as every-day steroids over the long term in a group of patients with undifferentiated polymyositis, with less serious long-term side effects.
Source: Uchino M, et al. Long-term outcome of polymyositis treated with high, single-dose, alternate-day prednisolone therapy. Eur Neurol 2012;68:117-121.
Glucocorticoids remain the cornerstone of initial therapy for polymyositis, despite the absence of placebo-controlled trials demonstrating their effectiveness, and despite the fact that older studies did not demonstrate any improvement in survival. Long-term, daily glucocorticoids result in a host of side effects, and hence alternate-day dosing is preferable. Over the short term, alternate-day dosing has been shown to be as effective as daily dosing to achieve remission.1 Is the same true for the long-term outcome of polymyositis?
Among 235 patients with inflammatory myopathy seen between 1970-2009 at the Department of Neurology, Kumamoto University, Kumamoto, Japan, 161 had biopsy-proven polymyositis, of which 149 received either alternate-day (n = 35) or daily-dose prednisolone. Of these, 115 were followed for more than 10 years or until death, encompassing 32 alternate-day and 83 daily-dose patients, who served as the subjects of this study. Patients were excluded if there was a suspicion of inclusion body myositis, including finger, wrist flexor, or quadriceps weakness on examination, or rimmed vacuoles and amyloid deposits pathologically. Paraneoplastic necrotizing myopathy and statin-induced myopathy patients similarly were excluded, as were those who did not demonstrate classical findings on needle electromyography, including positive waves and small amplitude, short duration, polyphasic motor unit potentials. Alternate-day dosing comprised 2 mg/kg prednisolone every other day, which was decreased by 10 mg approximately every month until a dose of 10-30 mg was achieved and maintained. Daily-dose patients underwent a similar protocol beginning at 1 mg/kg daily. Both groups were given a low-salt diet, vitamin D and potassium supplements, and anti-ulcer agents. Clinical outcome measures included manual muscle testing score using the Medical Research Council method and the six grade disability score. Statistical analysis comprised Pearson's X2 and log-rank tests with a difference of P < 0.05 considered significant.
Alternate-day and daily-dose groups were comparable with respect to age, disability grade, and presence of malignancy or other collagen vascular disease. Response rates were comparable between the groups, but the incidence of diabetes was significantly higher in the daily-dose group. Other adverse effects, including hypertension, hyperlipidemia, infection, osteoporosis, and psychiatric symptoms, were slightly higher in the daily-dose patients, though not significantly so. Survival rates at 20 years were significantly higher in the alternate-day group. Alternate-day prednisolone appears to be as efficacious, in polymyositis, as daily prednisolone, with fewer adverse effects, and may be considered as an initial therapeutic option.
Commentary
Corticosteroids alone are often inadequate to treat polymyositis. Other immunosuppressive agents, including azathioprine, methotrexate, mycophenolate mofetil, rituximab, cyclosporine, cyclophosphamide, and tacrolimus, are commonly used but have never been proven efficacious in controlled clinical trials. Randomized, controlled trials have shown intravenous immunoglobulin (IVIG) to be effective in refractory polymyositis, given in the standard dose of 2 gm/kg over 2-5 days.2 Although rarely used as initial therapy, when combined with corticosteroids, IVIG has been demonstrated to improve strength and lower creatine kinase levels compared to placebo. Hence, an approach to the treatment of polymyositis might begin with high-dose prednisone, either daily or on alternate days, followed by IVIG, azathioprine, methotrexate, or mycophenolate mofetil when needed for their steroid sparing effects. In refractory patients, rituximab, cyclosporine, cyclophosphamide, or tacrolimus would be the next option.
References
1. Uchino M, et al. High single-dose alternate-day corticosteroid regimens in treatment of polymyositis. J Neurol 1985;232:175-178.
2. Wang DX, et al. Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: A systematic literature review. Clin Rheumatol 2012;31:801-806.
An alternate-day steroid protocol appears to be just as efficacious as every-day steroids over the long term in a group of patients with undifferentiated polymyositis, with less serious long-term side effects.Subscribe Now for Access
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