CO:01:4 | Identify predictors of relapse in idiopathic inflammatory myopathies: insights from an international cohort

Cristina Bochicchio^1|2, Maria Rosa Pellico^1|2, Claudia Iannone^1|2, Lekshmi Minikumari Rahulan³, Marco Fornaro⁴, Ilaria Cavazzana⁵, Edoardo Conticini⁶, Musataka Musataka⁷, Akira Yoshida⁷, Silvia Cavalli^1|2, Silvia Grazzini⁶, Giulio Fraticelli⁸, Alessia Gatti⁵, Giulio Lopinto⁴, Paolo Semeraro⁵, Veronica Batani⁸, Thomas Patric Sheeran⁹, Florenzo Iannone⁴, Giacomo De Luca⁸, Roberto Caporali^1|2, Latika Gupta^9|10|11, Nicoletta Del Papa². | ¹Department of Clinical Sciences and Community Health, University of Milano; ²Department of Rheumatology and Medical Sciences, ASST Gaetano Pini-CTO Institute, Milano, Italy; ³Rheumatology "Sanjay Gandhi" Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ⁴Unit of Rheumatology, Department of Precision and Regenerative Medicine, Area Jonica, University of Bari; ⁵Rheumatology and Clinical Immunology Unit, ASST Spedali Civili di Brescia; ⁶Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy; ⁷Department of Allergy and Rheumatology Nippon Medical School Graduate School of Medicine, Tokyo, Japan; ⁸Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milano, Italy; ⁹Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK; ¹⁰Francis Crick Institute, London, UK; ¹¹School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, UK

Background. Idiopathic inflammatory myopathies (IIM) are a group of rare and heterogeneous diseases. One of the greatest challenges in IIM management is defining and predicting disease flares, which are inconsistently characterized across studies. The aim of the study was to identify predictors of relapse in a retro-prospective, multi-centric IIM cohort during the first two years of disease.

Methods. Patients with IIM subsets—dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), connective tissue disease-associated IIM (CTD-IIM), or immune-mediated necrotizing myopathy (IMNM)—were included if >=18 yrs and with >= 2 years of follow-up. Relapse was defined as a change in disease activity requiring escalation of immunosuppressive therapy and/or steroids. Patients were classified as monocyclic (no relapse in the first 2 years), polycyclic (>=1 relapse in the first 2 years), or chronic continuous. Clinical characteristics across subgroups were compared using chi-square, Mann–Whitney U, or Student’s t-test. Predictors were identified through multivariable logistic regression.

Results. Of 297 screened patients, 91 were excluded due to missing data. A total of 206 patients were included (155 female; median age at diagnosis 46.9 years). 82 (39.8%) were DM, 56 (27.2%) ASyS, 40 (19.4%) CTD-IIM, 14 (6.8%) PM, and 14 (6.8%) IMNM. During the first 2 years of disease, 84 patients (40.8%) had monocyclic course, 67 (32.5%) polycyclic course, and 55 (26.7%) chronic continuous course. No significant differences in disease course distribution were observed across IIM subsets, although PM and IMNM were more frequently associated with chronic or relapsing patterns (64.2% vs. 35.8%). Myositis autoantibodies were not significantly linked to any disease course. Relapses occurred despite stable treatment for over one year in approximately one-third of cases. Most relapses involved muscle (61.9%), particularly in PM/IMNM (89%), whereas the frequency was notably lower in ASyS (43.2%), where ILD was the leading cause of relapse (61.4%). Refractory disease was the predominant phenotype in PM/IMNM (55.6%) and ASyS (52.3%), while drug tapering was most frequent cause implicated in DM (30%) and CTD-IIM (31%). Muscle and cardiac involvement at baseline were less frequent in monocyclic patients. A more severe disease phenotype—reflected by higher levels of muscle enzymes, and both PtGA and PhGA—was more commonly associated with non-monocyclic disease. Notably, non-monocyclic patients had received baseline low-dose steroids (<0.25 mg/kg; 78.9% vs. 21.1%, p = 0.019) and intravenous immunoglobulins (10.0% vs. 26.0%, p = 0.004). Multivariable analysis confirmed baseline muscle involvement, CK levels, and PtGA as independent predictors of relapse. -

Conclusions. In this large, diverse IIM cohort, non-monocyclic disease (polycyclic and chronic continuous) was associated with baseline myositis, higher serum muscle enzymes, higher global activity scores, and lower steroid induction dosage. These findings highlight the potential value of flare predictors and advocate for standardized definitions of disease activity/relapse in IIM.