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Inflammatory myopathies may occur with malignancies or collagenosis (lupus erythematosus, rheumatoid arthritis, overlap syndrome, or mixed connective tissue disease) or be associated with retroviral disease.1 Idiopathic inflammatory myopathies may present as dermatomyositis, inclusion body myositis, or polymyositis.
Most patients with polymyositis respond well to pulse treatment with corticosteroids. However, this treatment is usually restricted to short periods of time in an effort to contain severe bouts of the disease. A more chronic term of corticosteroid treatment is often desirable but this approach is complicated by untoward side effects and by the tolerability of the patient. Most authors recommend a combination of azathioprine and low doses of corticosteroids. If this regimen fails, ciclosporin A, immunoglobulins, or cyclophosphamide is recommended.2 β Interferons are a new group of immunomodulatory drugs widely used for treatment of patients with multiple sclerosis, a disease of probable autoimmune origin.3 However, no data are available on the efficacy of β interferons in the treatment of other autoimmune diseases.
Here we report the results of treatment of a patient with a longstanding history of polymyositis with interferon β-1a.
At the age of 15 years, the female patient noticed leg weakness associated with muscular pain in her calves during physical exercise. Laboratory investigation found a serum creatine kinase (CK) concentration of 9000 U/l. Necrotising myositis was diagnosed based on muscle biopsy and corticosteroid treatment was initiated. This treatment was initially well tolerated and the symptoms resolved. Attempts to discontinue the corticosteroid treatment led to recurrent exacerbations of the disease. Treatment was therefore initiated with second and third line immunosuppressant and immunomodulatory drugs (azathioprine, ciclosporin A, intravenous immunoglobulins, methotrexate) in an attempt to contain disease activity and to taper corticosteroids below the cushing level. When the patient developed spontaneous fractures, all treatment was halted; however, the patient continued to deteriorate clinically. Thus, cyclophosphamide pulse therapy in combination with corticosteroid treatment was initiated. Although each pulse reduced the serum CK from approximately 3000 U/l to 1000 U/l, the reduction was not sustained. During the course of the disease, two hospitals performed biopsies 3 and 11 years after the onset of symptoms. Both biopsies confirmed the diagnosis of polymyositis that showed a mixed lymphocytic, monocytic, and mononuclear infiltrate. No sign of a storage disease or inclusion body myositis could be detected. At the age of 32 years, 17 years after the onset of symptoms, she was referred to our hospital.
On admission the patient was able to walk a maximum of 50 m with the help of aids, climb two steps, and stand with straightened knees. Longer distances required the use of a wheelchair. Physical examination showed proximal accentuated weakness of the limbs with predominant involvement of both legs. The deep tendon reflexes were reduced in the upper extremities and absent in the lower ones. The remaining physical examination was unremarkable. The patient refused additional diagnostic procedures including a re-biopsy and electromyography.
The patient was administered 22 μg of interferon β-1a subcutaneously (Rebif™, Serono, Geneva, Switzerland) every other day. She tolerated the treatment well and steroid treatment was stopped permanently. After three and a half years of follow up with interferon β-1a treatment, CK concentration has stabilised at 600–1000 U/l and her severe symptoms have abated substantially. At her last visit, the patient was no longer confined to a wheelchair, walked inside her apartment without aid, and could climb one set of stairs. For longer distances she was still dependent on two walking aids.
This is, to the best of our knowledge, the first report of interferon β-1a treatment in polymyositis. Interferon β-1a treatment was initiated because it was a course of action that had not been tested before and other conventional immunosuppressive treatments proved ineffective or caused unacceptable side effects in this patient. Steroid treatment could be discontinued shortly after treatment with interferon β-1a was started. Moreover, disease activity was controlled for three years without requiring corticosteroid treatment, suggesting that beta interferons have utility in patients who require long term treatment of the disease. Since the interferon β-1a treatment has never been stopped, we can not formally exclude the possibility that the improvement reflects the natural history of the disease. However, we believe this to be highly unlikely given the longstanding history of the disease in this patient. Controlled clinical trials are necessary to fully test the efficacy of interferon β-1a in the treatment of inflammatory myopathies. Indeed, one multicentre trial with interferon β-1a is underway.2 This case study thus suggests that interferon β-1a may be a new therapeutic option in autoimmune diseases beyond multiple sclerosis, particularly in cases where established steroid regimens fail.
We thank Dr. Bogumil for helpful discussion of the manuscript.
Competing interests: AD and WB have both received support for attending conferences and organising education; in addition, AD has received speaker fees and holds a research grant from Serono. Similar support has been given to both authors by Schering and Biogen as well as Teva (AD) and Aventis (WB), companies manufacturing immunomodulatory drugs for the treatment of multiple sclerosis. No support has been granted for the treatment of the patient described here.
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