The idiopathic inflammatory myopathies are rare disorders with significant heterogeneity in their clinical phenotypes. Therapy with glucocorticoids (GC) is generally initiated with prednisone at a dose of 1 mg/kg per day, often in divided doses and generally not exceeding 80 mg daily. Prednisone is slowly tapered to a minimum effective dose by tapering the existing dose by 20-25% monthly. It is rare for patients to receive glucocorticoid monotherapy as most patients need another immunosuppressive drug due to refractory disease, flares with steroid tapering or to minimize GC side effects. Severely ill patients with marked weakness, rapidly progressive ILD or other systemic problems such as severe dysphagia should receive pulse intravenous methylprednisolone (1000 mg daily for three consecutive days) followed by the high dose oral steroids in combination with a 2nd line immunosuppressive drug.
Methotrexate can be given orally or subcutaneously in doses up to 25 mg/week. A randomized, open-label, multicenter study of methotrexate in Europe is under the direction of Dr. Jiri Vencovsky who is investigating the efficacy and safety of combined methotrexate/glucocorticoid treatment with glucocorticoid treatment alone. Azathioprine was shown to be effective in a previously published randomized trial of 16 patients with PM, and patients treated with a combination of azathioprine and prednisone had better functional status and required less prednisone for maintenance 3 years later. Although, one must be careful in treating myositis patients with a propensity for ILD, there is no evidence that methotrexate leads to more pulmonary toxicity in patients with myositis-related ILD. Some prefer azathioprine in such patients. A randomized, crossover study published many years ago showed that a combination of oral methotrexate and azathioprine might be beneficial for patients with resistant myositis, including those who failed to respond to either agent alone.
Several small case series have demonstrated efficacy for MMF in treating refractory PM and DM including uncontrolled studies suggesting that this agent may help patients with refractory cutaneous features of DM. In addition, MMF is being increasingly used in myositis-associated ILD or any form of ILD seen in patients with various connective tissues diseases.
Cyclosporine has been used to treat refractory myositis as well as ILD and in a randomized open-label controlled trial, the administration of cyclosporine or methotrexate added to glucocorticoids led to improved muscle strength but patients treated with methotrexate showed no better response than cyclosporine. Studies from Japan showed that the combination of cyclosporine and glucocorticoids resulted in better early and long-term outcome in many patients with myositis-associated ILD than glucocorticoids alone. Similarly, tacrolimus, a second generation calcineurin inhibitor that binds to FKBP-12, has been reported to benefit patients with both myositis as well as those with coexisting ILD and anti-synthetase autoantibodies. Cyclophosphamide is generally given to patients with progressive ILD or those with myositis and systemic vasculitis as it is an alkylating agent with the potential for later malignancy.
In the largest clinical trial of rituximab in myositis, the Rituximab in Myositis (RIM) trial, 195 patients with refractory myositis failing steroids and at least one other immunosuppressive agent (75 with PM, 72 with DM, and 48 with juvenile DM) were randomized to receive two 1 gram rituximab infusions. Although the group treated earlier did not demonstrate a more rapid response to therapy than the group treated 8 weeks later (primary outcome not met), 83 percent of the patients met the pre-established definition of improvement and a significant steroid-sparing effect was reported. A subsequent analysis of the RIM cohort noted that the presence of an anti-synthetase autoantibody and anti-Mi-2 autoantibodies along with the juvenile DM subset and lower disease damage strongly predicted clinical improvement. In addition, rituximab has been reported as efficacious in several other case series including those possessing autoantibodies targeting signal recognition particles, a subset characterized by severe myositis.
IVIg, an immunomodulatory agent, can also be administered in a subcutaneous form and is given for severe cutaneous manifestations of DM as well as for patients with oropharyngeal dysphagia and in the setting of active myositis with concomitant infection.
Disclosure of Interest C. Oddis Consultant for: Questcor