Rituximab therapy for myopathy associated with anti–signal recognition particle antibodies: A case series

Abstract

Objective The myopathy associated with anti-signal recognition particle (SRP) is a severe necrotizing immune-mediated disease characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor responsiveness to traditional immunosuppressive therapies. Reports on the efficacy of B cell depletion therapy for anti-SRP associated myopathy are mixed. We describe eight patients with anti-SRP associated myopathy and their response to treatment with the anti-CD20 monoclonal antibody rituximab. Methods We identified eight patients with myopathy who tested positive for anti-SRP antibodies by immunoprecipitation and were treated with rituximab as part of clinical care. We reviewed their medical records to assess clinical, serologic, and histologic characteristics and response to therapy. In five patients, serum was collected before and after rituximab therapy. Autoantibodies were detected by immunoprecipitation and quantitated by densitometry, and the percent decreases in anti-SRP autoantibody levels were calculated. Results Six of eight patients who had been refractory to standard immunosuppressive therapy demonstrated improved manual muscle strength and/or decline in CK levels as early as two months after rituximab treatment. Three patients sustained the response for twelve to eighteen months after initial dosing. All patients were continued on adjunctive corticosteroids, but dosages were substantially reduced after rituximab. Quantitative levels of serum anti-SRP antibodies also decreased after rituximab treatment. Conclusions B cell depletion therapy with rituximab is effective for patients with myopathy associated with anti-SRP. The substantial decrease in anti-SRP antibody levels after rituximab treatment also suggests that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy.

Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy

“…Preliminary observations suggest that B celltargeting therapies, such as anti-CD20, may be efficient in otherwise-treatment-resistant anti-SRP-positive patients (8,41). Since there are very few lymphocytic infiltrates in the muscle of these patients, B celltargeting therapies presumably act on the autoreactive B cell response, which may include antigen presentation to T cells, cytokine production, and/or autoantibody secretion.…”

Inflammatory Muscle Diseases

“…65 Patients with anti-Jo-1, antiMi-2, or anti-SRP antibodies seem more likely to have a response. 66,67 Tumor necrosis factor inhibitors (infliximab, adalimumab, and etanercept) are ineffective and may worsen or trigger disease. 68 Other biologics that may be considered as experimental treatment include alemtuzumab, which is reportedly effective in polymyositis 69 ; anti-complement C3 (eculizumab), which is effective in complement-mediated diseases and may be effective for the treatment of dermatomyositis and necrotizing autoimmune myositis; anti-interleukin-6 (tocilizumab) 70 and anti-interleukin-1 receptor (anakinra), 71 which have been effective in anecdotal cases; anti-interleukin-17; and antiinterleukin-1β (gevokizumab), which is being evaluated in an ongoing trial (EudraCT number, 2012-005772-34).…”

Paraneoplastic necrotizing myopathy in association with metastatic malignant melanoma: two case reports and a review of the literature

“…Anti-SRP subjects have unique clinical features, including more severe myopathy with dysphagia, very high CK levels, and better response to steroid therapy [3] . Two recent case series have suggested that anti-SRP levels do correlate with disease severity, and may serve as a marker of poor prognosis [13,14] . Additionally, a recent study identified anti-HMGCoA reductase autoantibodies in 63% of patients with necrotizing autoimmune myopathy [15] .…”