[Skip to Navigation]
Sign In
October 2015

Idiopathic Inflammatory Myopathy Treated With High-Dose Immunoablative Cyclophosphamide—A Long-term Follow-up Study

Author Affiliations
  • 1Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA Neurol. 2015;72(10):1205-1206. doi:10.1001/jamaneurol.2015.1425

To our knowledge, this is the first report of the use of high-dose immunoablative cyclophosphamide (HiCy) therapy in the absence of stem cell rescue in patients with idiopathic inflammatory myopathy.

Report of a Case

The clinical presentation of the patient has been described elsewhere (case number 8 in the article by Valiyil et al1). Briefly, the patient was a woman in her 30s who presented with a 5-month history of progressive proximal muscle weakness, low-grade fevers, and weight loss. Initial workup revealed an elevated creatine kinase (CK) level (8495 U/L; to convert to microkatals per liter, multiply by 0.0167), an irritable myopathy on electromyography, and a necrotizing myopathy on muscle biopsy. Before presentation to our center, she was treated with oral prednisone, 60 mg per day for 2 months, with minimal improvement in muscle strength. At presentation, neurological examination demonstrated symmetrically reduced arm abduction (4/5), hip flexion (4−/5), knee flexion (4/5), and neck flexion (3/5) muscle strength. The serum test result for autoantibodies to signal recognition particles 72, 54, and 19 was positive. Suspecting potential concomitant steroid-induced myopathy, prednisone was tapered down to 30 mg per day and azathioprine was started at 100 mg per day and titrated up to 150 mg per day for 3 months. Subsequently, owing to rising muscle enzymes, azathioprine was replaced with methotrexate at 20 mg per week and continued for 3 months along with prednisone. Again, she continued to worsen clinically and was switched to intravenous immunoglobulin.

A 6-month course of intravenous immunoglobulin at 2 g/kg per month failed to halt her progression, and she developed further weakness. At this time, magnetic resonance imaging of the thighs showed bilateral 2−3+ edema with 1+ atrophy throughout hip rotators and medial and posterior compartments of the thigh (Figure, A). Afterward, she was treated with rituximab (1000 mg at days 0 and 14). She continued to experience worsening lower extremity weakness. Eventually, she received 6 plasmapheresis treatments with minimal improvement.

Figure.  T2 Short Tau Inversion Recovery Magnetic Resonance Image of the Thigh Muscles
T2 Short Tau Inversion Recovery Magnetic Resonance Image of the Thigh Muscles

A, Eight months before high-dose immunoablative cyclophosphamide (HiCy) therapy, significant muscle edema in posterior and lateral compartments of both thighs is evident. B, Twenty-one months after HiCy therapy, the muscles of the posterior and medial compartments have been largely replaced by adipose tissue/fibrosis, but there is no evidence of acute inflammation.

During the entire period of follow-up at our center, she required 20 to 30 mg daily of oral prednisone. Neurological examination prior to the onset of HiCy therapy revealed symmetrically reduced arm abduction (4−/5) and hip flexion strength (2/5) and her CK level was 2920 U/L. Given progressive muscle weakness in the absence of a robust response to any immunosuppression, she was treated with HiCy, 50 mg/kg per day, for 4 consecutive days and supportive care, as previously described.2 Although she developed neutropenic fever 9 days later, she recovered successfully. She did not require red blood cell or platelet transfusion, and her neutropenia ultimately resolved 2 weeks after HiCy dosing. Muscle strength gradually improved to normal, and her CK level decreased to 537 U/L within 7 months of treatment. A repeated magnetic resonance image was performed 21 months after treatment (Figure, B). Her steroids were tapered off within 2 years of HiCy therapy. At her last visit, she had minimal residual weakness (4+/5 deltoids and hip flexors), which did not affect her activities of daily living. She has remained in clinical remission while not taking any immunosuppressive therapies, including glucocorticoids, with her most recent CK level normal at 100 U/L 6 years after HiCy treatment.


High-dose immunoablative cyclophosphamide has been successfully used in the treatment of a variety of autoimmune diseases including multiple sclerosis, myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy.3-5 The initial response rate to HiCy therapy in refractory severe autoimmune diseases exceeds 90%,2 but only 20% remain disease-free at 5 years after treatment.6 In addition, the durability of the response may vary depending on the underlying autoimmune disease.2 For example, patients with pemphigus and lupus tend to have a less durable response following HiCy therapy than patients with autoimmune hemolytic anemia.2 Our patient achieved a durable remission after HiCy therapy and remains in remission 6 years after her initial HiCy treatment. This finding suggests that HiCy therapy may be effective and cause more durable remission in refractory idiopathic inflammatory myopathy for which conventional treatments are insufficient.

Back to top
Article Information

Corresponding Author: Lisa Christopher-Stine, MD, MPH, Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Ave, MFL Center Tower, Ste 4500, Baltimore, MD 21224 (lchrist4@jhmi.edu).

Conflict of Interest Disclosures: Dr Christopher-Stine reports serving on the advisory board; receiving honoraria from Novartis, Mallinckrodt, Walgreens, and Medimmune; and having membership in the advisory board of Idera. She has intellectual property rights in connection with Inova Diagnostics. No other disclosures were reported.

Funding/Support: This study was supported by the Huayi and Siuling Zhang Discovery Fund.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Valiyil  R, Casciola-Rosen  L, Hong  G, Mammen  A, Christopher-Stine  L.  Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series.  Arthritis Care Res (Hoboken). 2010;62(9):1328-1334.PubMedGoogle ScholarCrossref
DeZern  AE, Petri  M, Drachman  DB,  et al.  High-dose cyclophosphamide without stem cell rescue in 207 patients with aplastic anemia and other autoimmune diseases.  Medicine (Baltimore). 2011;90(2):89-98.PubMedGoogle ScholarCrossref
Krishnan  C, Kaplin  AI, Brodsky  RA,  et al.  Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis.  Arch Neurol. 2008;65(8):1044-1051.PubMedGoogle ScholarCrossref
Drachman  DB, Adams  RN, Hu  R, Jones  RJ, Brodsky  RA.  Rebooting the immune system with high-dose cyclophosphamide for treatment of refractory myasthenia gravis.  Ann N Y Acad Sci. 2008;1132:305-314.PubMedGoogle ScholarCrossref
Brannagan  TH  III, Pradhan  A, Heiman-Patterson  T,  et al.  High-dose cyclophosphamide without stem-cell rescue for refractory CIDP.  Neurology. 2002;58(12):1856-1858.PubMedGoogle ScholarCrossref
Dezern  AE, Styler  MJ, Drachman  DB, Hummers  LK, Jones  RJ, Brodsky  RA.  Repeated treatment with high dose cyclophosphamide for severe autoimmune diseases.  Am J Blood Res. 2013;3(1):84-90.PubMedGoogle Scholar