Rituximab for patients with myopathy associated with anti–signal recognition particle antibodies: Comment on the article by Valiyil et al


Rituximab for Patients with Myopathy Associated with Anti-Signal Recognition Particle Antibodies: Comment on the Article by Valiyil et al

To the Editors:

We read with interest the study by Valiyil et al, published recently in Arthritis Care & Research, concerning 8 patients treated with rituximab for a refractory myositis associated with anti–signal recognition particle (anti-SRP) antibodies (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;62:1328–34). Such reports are rare, and we would like to describe the successful long-term management of 2 more patients with this disease. Between 2007 and 2009, we discovered 4 cases, all of African Caribbean origin, of inflammatory myositis with anti-SRP antibodies in our department of medicine in Martinique. Two of these patients had a severe presentation and a corticosteroid resistance that motivated us to use rituximab.

In the first case, a 22-year-old woman without any previous medical history was hospitalized in December 2008 for a 1-month rapidly progressive proximal severe paraparesia with myalgia, swollen muscles, dyspnea, and facial edema. She developed dysphagia during the first days of her hospitalization. Her muscle strength was initially grade 2/5 in the proximal upper extremity (grade 5/5 distal) and grade 2/5 in the proximal lower extremity (grade 4/5 distal). The creatine kinase (CK) level was 23,780 IU/liter. The laboratory test results showed an anti-SRP antibody. Echocardiography and a computed topography scan of the lung were normal; electromyography was not contributive. A muscle biopsy sample showed a large necrotizing myopathy with degenerating and regenerating fibers and limited inflammation with a slight class I major histocompatibility complex immunostaining. Three daily pulses of 1,000 mg methylprednisolone, methotrexate (0.3 mg/kg weekly), intravenous immunoglobulin (IVIG; 2 gm/kg monthly), and high-dose oral corticosteroids provided limited improvement. In October 2009, the CK level decreased to 1,200 IU/liter, whereas muscle strength was grade 3/5 in the proximal upper and lower extremities (no progress in the distal extremities). Therefore, we treated the patient with rituximab (2 doses of 1 gm) with readministration in May 2010. The CK level stayed the same, but proximal weakness improved to grade 4/5 in the legs and to grade 5/5 in the arms. In September 2010, the patient was able to get out of bed and walk alone. The IVIG infusions were therefore stopped in December 2009, and the corticosteroids were reduced from 15 mg to 6 mg daily. Methotrexate treatment remained at the same dose. The patient's CD19 and CD20 counts were not detectable after 6 months of rituximab.

The second case was a 51-year-old woman who was treated in July 2007 with high doses of oral corticosteroids and IVIG (2 gm/kg, with retreatment in October 2007) for a polymyositis with proximal muscle weakness of grade 3/5. The CK level was 36,560 IU/liter, and a muscle biopsy sample showed a necrotizing myopathy with atrophy and a slight class I major histocompatibility complex immunostaining. In December 2007, she was referred to our unit with a 1-month proximal muscle weakness of the extremities of grade 1/5 with severe disability. She experienced myalgia, dysphagia, and dysphonia. The CK levels were 36,000 IU/liter. Echocardiography results showed a myocarditis. An anti-SRP antibody was found. We did not perform any electromyography. Magnetic resonance imaging (MRI) of the proximal lower extremities showed a large muscle edema. She received a high dose of oral corticosteroids following 3 methylprednisolone (1 gm) treatments, IVIG (2 gm/kg monthly), and methotrexate (0.3 mg/kg weekly) with only limited clinical improvement after 2 months (proximal strength of the 4 extremities grade 2/5). We decided to treat her with 2 doses of 1 gm rituximab, and she received a new cycle of treatment every 6 months. Her strength improved just 4 months after the first infusion of rituximab. The patient's test results were clinically normal at 6 months and remain so currently, despite a persistent raised CK level between 400–1,100 IU/liter. The patient's CD19+ and CD20+ lymphocyte counts were undetectable. We stopped IVIG in 2010, which was 1 year after the beginning of rituximab.

So far, rituximab treatment may lead to a sustained remission in 10 (71%) of the now 14 published observations. Nine (64%) of these 14 severe patients are of African descent. However, to extrapolate that this disease is possibly more frequent or severe in this population is impossible without precise epidemiologic data. In conclusion, as in the article by Valiyil et al, these 2 new patients help support the fact that anti-CD20 therapy could be an interesting alternative to improve the outcome for patients experiencing severe anti-SRP myopathy.

Christophe Deligny MD*, Vincent Goëb MD, PhD*, Maryvonne Dueymes MD, PhD*, Valentine Kahn MD*, Véronique Dehlinger MD*, Georges Jean Baptiste MD*, Khadija Amarof MD*, Serge Arfi MD*, * Centre Hospitalier Universitaire de Fort de France Fort de France Cedex, France.