Advanced refractory polymyositis responding to infliximab

A. Anandacoomarasamy1, G. Howe1 and N. Manolios1,2

1 Department of Rheumatology, Westmead Hospital and 2 Department of Medicine, University of Sydney, Australia.

Correspondence to: N. Manolios, Department of Rheumatology, Westmead Hospital, Westmead, NSW 2145, Australia. E-mail: nickm{at}westgate.wh.usyd.edu.au

SIR, The reported dramatic response of a patient with polymyositis (PM) treated with infliximab, an anti-TNF{alpha} blocker, by Labioche et al. [1] and the strong protective effect of anti-TNF therapy in preventing necrosis in dystrophic muscle [2] prompted us to trial this drug in one of our patients with advanced refractory PM and severe functional impairment. Here, we confirm previous reports and show a remarkable improvement in this patient's symptoms after only two infusions.

A 66-yr-old woman was diagnosed with PM in 1989 after presenting with progressive proximal muscle weakness. She had no pulmonary involvement or skin involvement suggestive of dermatomyositis (DM). Initial investigations revealed elevated serum creatine kinase (CK) and erythrocyte sedimentation rate (ESR). Electromyographic (EMG) studies and muscle biopsy showed changes consistent with PM. She had an initial response to prednisone (up to 50 mg) and was maintained with varying doses of prednisone until 1999. During this period, azathioprine was used as a steroid-sparing agent and was ceased due to significant nausea and vomiting. In November 1999, she presented to us for re-evaluation and further management following a recent flare. A repeat muscle biopsy showed plentiful lymphocytes and ongoing myositis. There were no inclusion bodies noted on electron microscopy to imply inclusion-body myositis. She was given a methylprednisolone infusion and methotrexate was commenced. Methotrexate was ceased in February 2000 because of methotrexate-induced pneumonitis. Cyclosporin was then tried and ceased due to significant hypertension.

In May 2000, she experienced a further flare whilst remaining on prednisone alone. She was treated with intravenous immunoglobulin (IVIg; four consecutive days) but only had a short-lived response lasting 1 week. In October 2000, she was commenced on intravenous pulse cyclophosphamide (monthly, four courses). She had a poor response to cyclophosphamide, and leflunomide was commenced. Again, she had a partial response prompting further IVIg in June 2001. This resulted in improved muscle strength which was not sustained. Mycophenolate mofetil was commenced in April 2003 with some response.

In May 2004 she had worsening disease activity. She was wheelchair-bound and was not able to lift her arms above shoulder level, requiring assistance with daily activities. She remained on prednisone (10 mg) and mycophenolate (2 g). Intercurrent medical problems included coronary artery disease, hypertension, steroid-induced osteoporosis and dyspepsia. The patient was declining rapidly and a decision was made to treat her with infliximab after obtaining informed consent.

In order to measure clinical response, the Childhood Myositis Assessment Scale (CMAS) was applied in addition to standard manual muscle testing [3]. The CMAS has been validated to evaluate muscle strength, physical function and endurance in children with juvenile idiopathic inflammatory myopathy. Although it had been developed for children, it was felt that it could be reliably applied to our patient. The patient's disease had always been characterized by low CK levels during flares in the face of obvious histological changes, and therefore this was not adequate to demonstrate response. Given her prolonged course and poor muscle mass at this stage, we expected subtle clinical changes with minimal initial improvement in muscle strength.

Infusions (5 mg/kg) were administered at weeks 0, 2, 6 and 14. She continued with prednisone and mycophenolate. A remarkable response was observed in muscle strength after only two infusions. She could now walk and was able to lift her arms above her head. The CMAS scores demonstrated a response (Fig. 1). Function and endurance was still impaired but improving.



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FIG. 1. Childhood Myositis Assessment Scale (CMAS) scores prior to each dose of infliximab (maximum total score 52).

 
After the third infusion, she presented with a perforated peptic ulcer requiring laparotomy and oversew of the ulcer. She was hospitalized for 2 weeks post-operatively. This raised the interesting point of the relationship between anti-TNF treatment and aggravation of underlying peptic ulcer disease. With increasing use of anti-TNF therapy, it would be interesting to see if this is reported elsewhere. Although this raised an interesting question, we felt that anti-TNF therapy was unlikely to be the culprit as she had a long-standing history of peptic ulcer disease and prednisone use.

She received the fourth infusion as planned but had a decline in muscle function prior to this (Fig. 1). This raised a number of issues. The recent major surgery and prolonged hospitalization with resultant deconditioning could have contributed to the decline in response. Secondly, we had used the dosing frequency recommended in rheumatoid arthritis. The optimal dosing frequency (e.g. 4-weekly vs 8-weekly) and dose strength (e.g. 5 mg/kg vs 10 mg/kg) [4] has not been determined, and may be different in PM. We increased the infliximab dosing frequency to 4-weekly intervals to assess the role of dosing frequency. This resulted in continued gains in muscle strength with infusions 5 and 6 (Fig. 1). Our patient tolerated the drug well and has experienced no adverse events thus far.

The experience with anti-TNF therapy in PM and DM remains limited, with variable response to anti-TNF therapy (both infliximab and etanercept) having been described in case reports thus far [4–9]. In our case, we were encouraged by the initial response in our patient with long-standing debilitating PM who had tried and failed conventional and experimental DMARDs necessitating prolonged steroid use. Clearly, controlled studies are needed to clarify the important issues of response, appropriate dose and dosing intervals with the use of anti-TNF therapy in refractory PM and DM.

We thank Dr David Spencer, Rheumatology Department, Westmead Hospital for helpful discussion.

The authors have declared no conflicts of interest.

References

  1. Labioche I, Liozon E, Weschler B, Loustaud-Ratti V, Soria P, Vidal E. Refractory polymyositis responding to infliximab: extended follow-up. Rheumatology 2004;43:531–2.[Free Full Text]
  2. Grounds MD, Torrisi J. Anti-TNF (Remicade) therapy protects dystrophic skeletal muscle from necrosis. FASEB J 2004;18:676–82.[Abstract/Free Full Text]
  3. Huber AM, Feldman BM, Rennebohm RM et al. Validation and clinical significance of the childhood myositis assessment scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies. Arthritis Rheum 2004;50:1595–603.[CrossRef][ISI][Medline]
  4. Hengstman G, Van Den Hooven F, Van Egelen B, Barreta P, Netea M. Anti-TNF blockade with infliximab (Remicade) in polymyositis and dermatomyositis. Arthritis Rheum 2000;43:S193.
  5. Constantine K, Saadeh A. Etanercept is effective in the treatment of polymyositis/dermatomyositis which is refractory to conventional therapy including steroid and other disease modifying agents. Arthritis Rheum 2000;43:S193.
  6. Hengstman G, Van Den Hoogen FHJ, Barbera P et al. Anti-TNF blockade with infliximab (Remicade) in polymyositis and dermatomyositis. Eur Neurol 2003;50:10–5.[CrossRef][ISI][Medline]
  7. Roddy E, Courtney PA, Morris A. Non-Hodgkin's lymphoma in a patient with refractory dermatomyositis which has been treated with infliximab. Rheumatology 2002;41:1194–5.[Free Full Text]
  8. Uthman I, El-Sayed J. Refractory polymyositis responding to infliximab. Rheumatology 2004;43:1198–9.[Free Full Text]
  9. Sprott H, Glatzel M, Michel BA. Treatment of myositis with etanercept (Enbrel), a recombinant human soluble fusion protein of TNF-{alpha} type II receptor and IgG1. Rheumatology 2004;43:5224–5.
Accepted 7 December 2004





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