Refractory polymyositis responding to infliximab: extended follow-up

I. Labioche, E. Liozon, B. Weschler1, V. Loustaud-Ratti, P. Soria and E. Vidal

Department of Internal Medicine, University Hospital, Limoges and 1Department of Internal Medicine, University Hospital (Pitié-Salpétrière), Paris, France

Correspondence to: E. Liozon, Service de Médecine Interne A, CHRU Dupuytren 2, rue Martin Luther-King, 87042 Limoges, France. E-mail: eric.liozon{at}unilim.fr

SIR, The management of patients with dermatomyositis (DM) or polymyositis (PM) who fail to respond durably to conventional treatments remains difficult [1, 2]. We report the case of a 63-yr-old woman with refractory PM that dramatically responded to the addition of anti-TNF-{alpha} agent infliximab.

A 63-yr-old woman presented in August 2000 with a 3-month history of gradually deteriorating proximal muscle weakness, diffuse muscle tenderness, dyspnoea on exertion and weight loss. Physical examination revealed a symmetrical proximal muscle weakness in the upper and lower extremities, as well as trunk muscle weakness, making her unable to get up from squatting or supine positions. ‘Velcro’ crackles were heard in the lung bases but the dermatological manifestations characteristic of DM were not seen. Laboratory studies revealed elevated serum creatine kinase (CK) (6547 IU/l, normal value <190 IU/l) and aldolase of 57 IU/l (normal value <8 IU/l). The erythrocyte sedimentation rate was 80 mm/h. Autoantibody screening yielded negative results.

Electromyographic (EMG) studies and deltoid muscle biopsy revealed abnormalities consistent with PM. Interstitial lung disease was also demonstrated (vital capacity 65%). Additional work-up for underlying neoplasm was unrevealing and a diagnosis of idiopathic PM was made.

The PM was refractory to corticosteroids alone (Fig. 1) but responded to additional treatment with intravenous immunoglobulins (monthly IVIg, 6 courses) allowing the reduction of the prednisone dose to 10 mg daily. However, a severe PM relapse occurred 3 months later. The prednisone dose was therefore increased to 20 mg/day and IVIg (three courses) was resumed, but this time yielded no response. Further addition of methotrexate (Mtx), 30 mg weekly, and later azathioprine (Aza), 150 mg daily, resulted only in partial improvement.



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FIG. 1 Patient's response to treatment, as assessed by serum CK measurements

 
In December 2001 she complained of severe muscle pain. She required assistance to walk and was barely able to sit on her bed without help. After discussion with the patient and obtaining her consent, treatment was commenced with infliximab (Remicade® 10 mg/kg). Infusions were given from January 2002 at weeks 0, 2, 4, 6 and 9, the rest of her treatment being pursued without dose adjustment. Impressive improvement in muscle strength was observed from the first infusion and further improvement was seen during the following 2 months. Similarly, the serum CK level slowly returned to normal. Shortly after the last infusion, EMG studies also showed improvement, with less spontaneous activity and larger compound motor action potential of longer duration. By then, the pulmonary function tests had almost normalized. In June 2003, 15 months after the last infliximab infusion, the patient only takes prednisone 6 mg/day and methotrexate 30 mg every other week. She feels healthy and is free of muscle or pulmonary symptoms, with no significant functional disability. Proximal muscle strength is 5/5 and the CK level is repeatedly within the normal range.

This patient was seriously ill for 18 months due to refractory PM, despite several lines of treatment, including combined high-dose steroids, Mtx and Aza, and IVIg. The patient's poor condition made us consider anti-TNF therapy. The severity of the disease and the absence of history of opportunistic infections led us to use infliximab at the dose of 10 mg/kg, as proposed by Hengstman et al. in a preliminary study on PM [3]. Infliximab was not only remarkably well tolerated but also led to a rapid and sustained improvement of the patient's clinical condition, contrasting with the failure of all prior therapies. Likewise, the CK level progressively normalized, and at the same time EMG and pulmonary changes consistently improved, allowing immunosuppressive agents to be considerably reduced or stopped. Thus, infliximab appeared to be the only agent that had the ability to control the PM in the long term, but a minor additional role for continuing treatment with Mtx and Aza cannot be ruled out.

Despite evidence that TNF-{alpha} could have a pivotal role in PM and DM [47], the experience with anti-TNF agents in this setting is still limited. Saadeh treated four female patients, aged 9 to 35 yr with etanercept. The DM or PM was refractory to corticosteroids and various disease-modifying treatments [8]. All patients responded quickly to etanercept, with three complete responses and one excellent, partial response, allowing three patients to discontinue all treatments. Hengstman et al. reported on two patients with previously untreated DM/PM with infliximab 10 mg/kg body weight every other week for 6 weeks [9]. The response was remarkable from the first infusion in both patients but the PM was not fully controlled at the end of study in 12 weeks. The authors of both studies claimed that none of their patients had any side-effects due to anti-TNF treatment. Finally, Roddy et al. described a 48-yr-old woman with refractory DM and underlying malignant lymphoma who was unsuccessfully treated with infliximab [10].

Our report not only provides further evidence that TNF-{alpha} blockade may result in rapid and dramatic control of polymyositis symptoms, even in the most refractory cases, but also demonstrates that the response may be sustained beyond the period of treatment. However, controlled studies are needed to determine the appropriate dose and magnitude of response to anti-TNF agents in the setting of refractory DM and PM.

The authors have declared no conflicts of interest.

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Accepted 22 October 2003