Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Rituximab Is An Effective Therapy for Anti-Signal Recognition Particle (Anti-SRP) Myopathy

Valiyil,  Ritu, Casciola-Rosen,  Livia, Hong,  Grace, Mammen,  Andrew, Christopher-Stine,  Lisa

Purpose:

The myopathy associated with anti-signal recognition peptide (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. Currently, 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 clinical response to treatment with the anti-CD20 monoclonal antibody rituximab.

Method:

We identified eight patients with myopathy who tested positive for anti-SRP antibodies by immunoprecipitation and had been treated with rituximab as part of clinical care between 2006 and 2009. We reviewed their medical records to assess clinical, serologic, and histologic characteristics of their muscle disease and response to therapy. In five of the eight patients, serum samples were also collected before and after rituximab treatment. In those patients, autoantibodies were detected by immunoprecipitation and quantitated by densitometry, and the percent decreases in anti-SRP autoantibody levels were calculated.

Results:

In our cohort, the mean age was 37 years, 75% were female, and 50% were African-American. All patients presented with severe, rapidly progressive proximal muscle weakness with myalgias, dysphagia, and high CK levels with a mean maximum CK of 18,900 IU/l (3,148–56,000 IU/L). Six of the eight patients refractory to standard immunosuppressive therapy demonstrated improved manual muscle strength and/or decline in CK levels as early as two months after receiving two doses of rituximab. 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. In four of the five patients tested, quantitative levels of serum anti-SRP antibodies also decreased after rituximab treatment.

Conclusion:

B cell depletion therapy with rituximab is an effective therapy for patients with anti-SRP myopathy. 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.

PatientCK prior to therapyHighest prednisone dose (mg/day)Prior treatmentsLowest prednisone dose post-therapyLowest CK post-therapyOutcome post B cell depletion, duration of remission
1271060AZA, MTX20622CK decline, improved strength, 10 months
21000160AZA, MTX, IVIg, plasma exchange5163Normalized CK, improved strength, 18 months
355040AZA, MTX, IVIg, MMF15126Normalized CK, improved strength, 19 months
4106380IVIg, plasma exchange5022Died 1 month later from pneumonia
5290080MTX, IVIg10963CK decline for 12 months, then re-dosed for increased CK
6210060MTX, MMF, IVIg301144CK decline, improved strength, 9 months
7125060MTX, MMFN/A1080CK decline, 5 months
8311060AZA, MTX, IVIg, plasma exchange152100CK decline for 6 months, persistent weakness

To cite this abstract, please use the following information:
Valiyil, Ritu, Casciola-Rosen, Livia, Hong, Grace, Mammen, Andrew, Christopher-Stine, Lisa; Rituximab Is An Effective Therapy for Anti-Signal Recognition Particle (Anti-SRP) Myopathy [abstract]. Arthritis Rheum 2009;60 Suppl 10 :811
DOI: 10.1002/art.25891

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