Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Anakinra in Patients with Refractory Idiopathic Inflammatory Myopathies
Dorph1, Christina, Dastmalchi1, Maryam, Alexanderson2, Helene, Ottosson3, Christina, Lindroos3, Eva, Nennesmo4, Inger, Lundberg1, Ingrid E.
Rheumatology Unit, Karolinska University Hospital and Karolinska Institutet. Stockholm, Sweden
Rheumatology Unit, Department of Medicine and Department of Physical Therapy. Karolinska Institutet, Stockholm, Sweden
Karolinska Institutet, Stockholm, Sweden
Division of Pathology, Karolinska University Hospital and Karolinska Institutet. Stockholm, Sweden
Earlier studies have shown an increased interleukin-1 (IL-1) expression in muscle tissue from patients with polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). The objective of this study was to investigate the efficacy and tolerability of treatment with the IL-1 blocking agent, anakinra, in patients with treatment-resistant inflammatory myopathies.
15 patients with refractory PM (6), DM (4) or IBM (5) were included in a 12-month open-label study and treated with 100 mg anakinra subcutaneously per day. All patients had stable concomitant immunosuppressive treatment such as prednisolone and methotrexate or azathioprine. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS) and for muscle performance, the functional index of myositis (FI) at 3, 6 and 12 months. Repeated muscle biopsies (months 0 and 6) were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I, IL-1a, IL-1b and IL-1 receptor antagonist (IL-1Ra).
8 women and 7 men who had definitive diagnosis of PM, DM or IBM with disease duration of 218 years were included. 9 patients completed the 12 month study. 11 patients completed 6 months, and 13 patients concluded 3 months. 7 patients fulfilled improvement criteria for disease activity (responders) according to IMACS definition (3 DM, 3 PM, 1 IBM). 5 had improved by 3 months (1 sustained until 6 months), 1 by 6 months (sustained until 12 months) and 1 by 12 months. Five were unchanged and three worsened (non-responders). FI improved >=20 % in 4 of the 7 responders (1 DM, 2 PM, 1 IBM). Two patients withdrew due to a local skin rash at the injection site. Other reasons for premature ending of the study were increased muscle symptoms in 2, headache in 1 and lack of efficacy in 1. Repeated biopsies were available in 14 patients. There were no statistically significant changes in mononuclear inflammatory cells, T cells, IL-1a, IL-1b and MHC class I between pre-treatment and post-treatment biopsies. All responders had IL-1Ra expression in the post-treatment biopsy but only 3 of 8 non-responders.
Treatment with anakinra had beneficial effects on clinical outcome measures including disease activity and muscle performance in some patients in this pilot study of previously treatment-resistant myositis. The clinical positive effects together with the observation of IL-1Ra expression in muscle tissue in more post-treatment biopsies of responders than non-responders need to be confirmed in a larger placebo-controlled trial.
To cite this abstract, please use the following information:
Dorph, Christina, Dastmalchi, Maryam, Alexanderson, Helene, Ottosson, Christina, Lindroos, Eva, Nennesmo, Inger, et al; Anakinra in Patients with Refractory Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheum 2009;60 Suppl 10 :589