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Original Investigation
December 2018

Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies

Author Affiliations
  • 1Centre de Recherche en Myologie, Unité Mixte de Recherche Scientifique 974, Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale, Paris, France
  • 2Département de Médecine Interne et Immunologie Clinique, Centre de Référence Maladies Neuro-Musculaires, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, DHUi2B, Paris, France
  • 3Département de Biostatistiques, Santé Publique et Information Médicale, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  • 4Institut Pierre Louis d'Epidémiologie et de Santé Publique, Université Pierre et Marie Curie–Paris 6, Sorbonne Universités, Groupe de Recherche Clinique–08, Epidémiologie et Evaluation des Maladies Ostéoarticulaires Inflammatoires et Systémiques, Paris, France
  • 5Sorbonne Universités, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Université Pierre et Marie Curie–Paris 6, Unité Mixte de Recherche Scientifique 1136, Paris, France
  • 6Service de Médecine Interne, Centre Hospitalier Universitaire, Lille, France
  • 7Service de Médecine Interne, Hôpital Belle-Isle, Metz, France
  • 8Département de Physiologie, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France
  • 9Service de Médecine Interne, Centre Hospitalier Universitaire Hôtel Dieu De France, Beirut, Lebanon
  • 10Laboratoire Immunochimie, Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
JAMA Neurol. 2018;75(12):1528-1537. doi:10.1001/jamaneurol.2018.2598
Key Points

Questions  Does the identification of myositis-specific autoantibodies suggest the potential for identifying subgroups of idiopathic inflammatory myopathies, and is a new classification system for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria warranted?

Findings  In this cohort study of 260 patients with idiopathic inflammatory myositis, 4 clusters (dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and anti-synthetase syndrome) were identified using unsupervised multivariate analyses. The developed decisional tree revealed that myositis-specific antibodies played a role in predicting the likelihood of belonging to a cluster.

Meaning  This classification scheme for identifying subgroups of idiopathic inflammatory myopathies suggests that use of a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.

Abstract

Importance  Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that subgroups of patients exist.

Objective  To develop a new classification scheme for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria.

Design, Setting, and Participants  An observational, retrospective cohort study was performed using a database of the French myositis network. Patients identified from referral centers for neuromuscular diseases were included from January 1, 2003, to February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260 adult patients with myositis who had complete data and defined historical classifications for polymyositis, dermatomyositis, and inclusion body myositis were enrolled. All patients were tested for anti–histidyl-ARN-t- synthetase (Jo1), anti–threonine-ARN-t-synthetase (PL7), anti–alanine-ARN-t-synthetase (PL12), anti–complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku, anti–polymyositis/systemic scleroderma (PMScl), anti–topoisomerase 1 (Scl70), and anti–signal recognition particle (SRP) antibodies. A total of 708 variables were collected per patient (eg, cancer, lung involvement, and myositis-specific antibodies).

Main Outcomes and Measures  Unsupervised multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in subgroups.

Results  Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1 (n = 77) included patients who were male, white, and older than 60 years and had finger flexor and quadriceps weakness and findings of vacuolated fibers and mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n = 91) regrouped patients who were women and had high creatine phosphokinase levels, necrosis without inflammation, and anti–SRP or anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune-mediated necrotizing myopathy (53 of 91 [58.2%]; 95% CI, 47.4%-68.5%; P < .001). Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2, anti–melanoma differentiation-associated protein 5 (MDA5), or anti–transcription intermediary factor-1γ (TIF1γ) antibodies, mainly corresponding with patients who had dermatomyositis (43 of 52 [82.7%]; 95% CI, 69.7%-91.8%; P < .001). Cluster 4 (n = 40) was defined by the presence of anti-Jo1 or anti-PL7 antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI, 76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50) confirmed the 4 clusters (Cohen κ light, 0.8; 95% CI, 0.6-0.9).

Conclusions and Relevance  These findings suggest a classification of idiopathic inflammatory myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome. This classification system suggests that a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.

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