Objective: To investigate efficacy, safety, and tolerance of high-intensity interval training (HIIT) versus standard low-moderate intensity home-based exercise (CON) to improve aerobic capacity, muscle endurance, and mitochondrial function in patients with recent onset, idiopathic inflammatory myopathies (IIM). Methods: Twenty-three patients with recent onset IIM were randomized into two groups: HIIT and CON. HIIT underwent 12 weeks of supervised high-intensity training, while CON followed a low-moderate intensity home-based exercise program. Outcomes included maximal exercise test (VO2peak, peak power, time-to-exhaustion TTE), mitochondrial protein expression in muscle biopsy serum levels of muscle enzymes (CK, LD, AST, ALT), muscle strength (MMT8) and disease activity (subset of MDAAT), before and after intervention. Results: HIIT resulted in a 16% increase in VO2peak L/min, significantly higher than the 1.8% change in CON (95% CI 0.1;0.47). Peak power and TTE also improved significantly more in HIIT, 18% and 23%, respectively, compared to CON, 8% and 12%, (95% CI 3.9;30.8 and 00:06;03:18, respectively). Muscle biopsies (HIIT n=7, CON n=6) showed increases (p<0.05) in central mitochondrial protein expression in HIIT but not in CON, suggesting enhanced mitochondrial function. Both groups maintained stable serum muscle enzymes indicating no increase in disease activity from the intervention. Muscle disease activity remained low and unchanged in both groups (95% CI -1.2;1.0), physician global activity and MMT8significantly improved within CON (95% CI -1.7;-0.26 and 0.1;3.9, respectively) but not in the HIIT group. Compliance with HIIT was high, and no adverse events were reported. Conclusion: HIIT is a highly effective and safe exercise intervention to improve aerobic fitness, muscle endurance, and mitochondrial function in patients with recent onset IIM. This approach should be considered as an adjuvant treatment in managing IIM, potentially enhancing the health for these patients.

I.E.L. has received research grants from Astra Zeneca and Janssen Pharmaceutica NV and has been serving on the advisory board for EMD Serono Research & Development Institute, Argenx, Pfizer, Galapagos, Chugai Pharmaceutical Co., Ltd; Novartis, Bristol Myers Squibb and Janssen Pharmaceutica NV and has stock shares in Roche and Novartis.

NCT03324152

I.E.L was supported by Swedish Research Council (2020-01378), ALF (FoUI-955086), Heart and Lung foundation (20220127) King Gustaf V 80-year foundation and Swedish Rheumatism Association. D.C.A was supported by King Gustaf V 80-year foundation (FAI-2022-0935), Stiftelsen Promobilia (A23059), Stockholm County research grant (ALF; FoUI-1002205) and Swedish Heart-Lung Foundation (20230594). H.A was supported by Swedish Research Council, Swedish Rheumatism Association, Promobilia Foundation, ALF (Agreement between central government and Stockholm Region)

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