Idiopathic inflammatory myopathies (IIMs) are rare, chronic disorders that may lead to substantial long-term morbidity, reduced quality of life, work disability and mortality. The aetiology of IIMs is largely unknown and therefore no causal treatment is available. There is an evidence for immune pathogenesis in a majority of cases, which include frequent association with disease specific autoantibodies, occasional combination with other connective tissue diseases, inflammatory infiltrates in the affected muscles, upregulation of HLA class I on muscle fibres; and detection of cytokines, their receptors, adhesion molecules and complement components in the affected muscles. Consequently, therapeutical approaches have been predominantly aimed at suppression of immune regulations. The development of effective and safe treatment protocols for IIMs has been hampered by relative rarity of these diseases; the absence of standardized assessment methods and limited previous collaboration between centres in clinical trials. IMACS (International Myositis Assessment and Study Groups) proposed core set measures and response criteria to be used in the new trials thus helping to standardise the assessment and comparison between trials.
Treatment of IIMs is usually initiated with glucocorticoids. There is an agreement that this is a mainstay for the treatment. Recent double blinded comparison of oral high-dose pulse dexamethasone with standard high daily prednisolone doses showed similar efficacy in the composite score, significantly longer median time to relapse with prednisolone and less side effects with dexamethasone treatment.
There have been only few controlled trials in IIMs performed, mostly with relatively low number of patients enrolled:
a double blind trial with azathioprine + prednisone as initial treatment of 16 polymyositis (PM) patients, which showed improvement in functional ability at 1 and 3 years after initiating treatment;
trial in 39 patients with plasmapheresis and leukapheresis, which failed to show efficacy;
administration of high i.v. immunoglobulin doses, which demonstrated beneficial effect in 15 dermatomyositis (DM) patients;
combination therapy with azathioprine and methotrexate as well as high dose of intravenous methotrexate with leucovorine rescue that showed some effectiveness in a cross over trial.
Open studies, case series or clinical experience suggest effectiveness of methotrexate, cyclosporine A, combination of methotrexate + cyclosporine, mycophenolate mofetil, tacrolimus, cyclophosphamide, and leflunomide.
A growing number of reports on the use of rituximab in IIMs show mostly positive results, particularly in patients with autoantibodies, including those with anti-SRP. Rituximab may be beneficial not only in muscle disease, but also in interstitial lung fibrosis in patients with antisynthetase syndrome. Large, multicenter, randomized study, with delayed phase design, using rituximab in 202 patients with PM, DM and juvenile DM did not achieve primary and secondary endpoints. However, 83% of patients met the definition of improvement criteria during the 44 week study. There was a significant corticosteroid sparing effect.
Anti-TNF treatment initially showed encouraging results. Newer studies were less positive and even the worsening of symptoms has been described in some patients. Very recent small double-blind study with etanercept, suggest some effect. All five patients receiving placebo were treatment failures (median time to failure was 148 days); 5/11 patients in the etanercept arm were successfully weaned off prednisone (median time to treatment failure was 358 days).
Treatment of sporadic inclusion body myositis has been largely unsuccessful with glucocorticoids or any immunosuppressive drugs. In a recent proof-of-principal study disease progression had been slowed after one series of alemtuzumab infusions.
Disclosure of Interest J. Vencovsky Grant/research support from: Institutional support from Ministry of Health 023728
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