SP0175 Heterogeneity of myositis and therapeutic consequences
Authors: J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Idiopathic inflammatory myopathies, or myositis, are a heterogeneous group of chronic inflammatory disorders affecting striated muscle leading to muscle weakness and impaired function. In addition, other organs are variably involved including the skin, lungs, heart, joints, and the gastrointestinal tract contributing to morbidity and mortality and to low health-related quality of life. Treatment decisions are often guided by the most prominently affected organ. The best recognised disease subsets are polymyositis (PM), dermatomyositis (DM), juvenile PM and DM, sporadic inclusion body myositis (sIBM), and immune-mediated necrotizing myopathy (IMNM). Muscle specific autoantibodies and muscle associated autoantibodies are frequently found in different forms of myositis and collectively they can be detected in approximately 80% adults and 60% children with myositis. They can identify homogeneous subsets, and have both diagnostic and prognostic value. The worst functional outcomes in terms of muscle involvement are often seen in patients with sIBM and with anti-SRP antibodies. sIBM patients are notoriously non-responsive to any treatment. Patients with anti-SRP display necrotizing myopathy in the muscle biopsy and treatment effect is usually low. In some patients an improvement or at least stabilisation can be achieved with the use of rituximab. The other patients with IMNM are those with anti-HMGCR antibodies and with statin medication history. Here the response to glucocorticoids (GC) and immunosuppressives (IS) is mostly good, although some patients require treatment with intravenous immunoglobulins (IVIGs) to which they respond very well even without concomitant GC. Patients with antisynthetase syndrome are characterised by the presence of interstitial lung disease, which may be in some cases the prevailing manifestation of the disease with only mild or none muscle weakness. Treatment is often successful with calcineurin inhibitors, mycophenolate mofetil (MMF), cyclophosphamide, or rituximab in these patients. Subgroup of patients with anti-NXP2 antibodies is characterised with strong association with calcinosis, both in children and adults, and the treatment represents a difficult problem. The effect was reported with the use of calcium channel blockers, warfarin, bisphosphonates, sodium thiosulfate, aluminium hydroxide, probenecid, colchicine as well as IVIGs, rituximab, abatacept, infliximab, and thalidomide. In any case, patients need to be treated aggressively if calcinosis progresses. Muscle disease in dermatomyositis is often responsive but the treatment of cutaneous manifestations may occasionally prove difficult. Antimalarials are usually prescribed first, sometimes in combination with systemic treatment using IVIGs, tacrolimus, MMF, or other IS. Patients with anti-MDA5 antibodies often develop clinically amyopathic or hypomyopathic DM, but at the same time their ILD can be rapidly progressive. Aggressive treatment with high dose GC and IS needs to be started early to increase the chance for survival. A proportion of patients with myositis manifests high type I interferon signature and the clinical trial suggests that these are the patients who benefit most from the treatment with interferon type I inhibition. In the future careful considerations based on the disease subsets, presence of autoantibodies, transcriptome and proteomic analysis will facilitate stratification into defined disease subtypes and help to guide targeted therapies in idiopathic inflammatory myopathies. <h3>Disclosure of Interest</h3> None declared