Rituximab Seems Promising In Refractory Myopathy

PHILADELPHIA — Six of eight patients with anti–signal recognition peptide myopathy that was refractory to standard immunosuppressive therapy showed clinical improvement with rituximab, according to findings from recent research.

Presenting the data at the annual meeting of the American College of Rheumatology, Dr. Ritu Valiyil noted that patients who responded to rituximab were able to lower their doses of corticosteroids.

Myopathy associated with anti–signal recognition peptide (anti-SRP) autoantibody is a severe, necrotizing, immune-mediated disease characterized by rapidly progressive proximal muscle weakness, myalgia, dysphagia, and markedly elevated serum creatine kinase (CK) levels. Patients generally respond poorly to conventional immunosuppressive therapies such as azathioprine, methotrexate, or intravenous immunoglobulin, says Dr. Valiyil, a rheumatology fellow at Johns Hopkins University, Baltimore.

A chart review identified eight patients who had failed standard immunosuppressive therapies who were then given two doses of rituximab, an anti-CD20 monoclonal antibody. The eight patients' mean age was 37 years; six were women, and four were black.

As soon as 2 months after receiving two doses of rituximab, six of the eight patients demonstrated improved muscle strength in their hands. Prior to treatment with rituximab, the mean creatine kinase was 1,835 IU/L, which declined to a mean of 777.5 IU/L after treatment. Three patients sustained the response for 12-18 months after initial dosing.

All patients on rituximab continued on adjunctive steroid therapy but were able to reduce their corticosteroid dose. The mean highest prednisone dose prior to receiving rituximab was 75 mg/day; the mean lowest dose after rituximab was 21 mg/day.

Autoantibodies were detected and quantitated in the serum samples collected before and after rituximab treatment in five patients. Four of the five patients showed a decrease in serum anti-SRP antibodies. The substantial decrease in anti-SRP antibody levels after rituximab suggest that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy, commented Dr. Valiyil.

“It should be noted that [many] of our patients were African American and we cannot rule out the possibility that there may be more of a response in this particular group of patients,” explained Dr. Lisa Christopher-Stine, a rheumatologist at Hopkins who is the principal investigator of the study.

Dr. Valiyil and Dr. Christopher-Stine reported having no financial conflicts of interest to disclose.

PHILADELPHIA — Six of eight patients with anti–signal recognition peptide myopathy that was refractory to standard immunosuppressive therapy showed clinical improvement with rituximab, according to findings from recent research.

Presenting the data at the annual meeting of the American College of Rheumatology, Dr. Ritu Valiyil noted that patients who responded to rituximab were able to lower their doses of corticosteroids.

Myopathy associated with anti–signal recognition peptide (anti-SRP) autoantibody is a severe, necrotizing, immune-mediated disease characterized by rapidly progressive proximal muscle weakness, myalgia, dysphagia, and markedly elevated serum creatine kinase (CK) levels. Patients generally respond poorly to conventional immunosuppressive therapies such as azathioprine, methotrexate, or intravenous immunoglobulin, says Dr. Valiyil, a rheumatology fellow at Johns Hopkins University, Baltimore.

A chart review identified eight patients who had failed standard immunosuppressive therapies who were then given two doses of rituximab, an anti-CD20 monoclonal antibody. The eight patients' mean age was 37 years; six were women, and four were black.

As soon as 2 months after receiving two doses of rituximab, six of the eight patients demonstrated improved muscle strength in their hands. Prior to treatment with rituximab, the mean creatine kinase was 1,835 IU/L, which declined to a mean of 777.5 IU/L after treatment. Three patients sustained the response for 12-18 months after initial dosing.

All patients on rituximab continued on adjunctive steroid therapy but were able to reduce their corticosteroid dose. The mean highest prednisone dose prior to receiving rituximab was 75 mg/day; the mean lowest dose after rituximab was 21 mg/day.

Autoantibodies were detected and quantitated in the serum samples collected before and after rituximab treatment in five patients. Four of the five patients showed a decrease in serum anti-SRP antibodies. The substantial decrease in anti-SRP antibody levels after rituximab suggest that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy, commented Dr. Valiyil.

“It should be noted that [many] of our patients were African American and we cannot rule out the possibility that there may be more of a response in this particular group of patients,” explained Dr. Lisa Christopher-Stine, a rheumatologist at Hopkins who is the principal investigator of the study.

Dr. Valiyil and Dr. Christopher-Stine reported having no financial conflicts of interest to disclose.

PHILADELPHIA — Six of eight patients with anti–signal recognition peptide myopathy that was refractory to standard immunosuppressive therapy showed clinical improvement with rituximab, according to findings from recent research.

Presenting the data at the annual meeting of the American College of Rheumatology, Dr. Ritu Valiyil noted that patients who responded to rituximab were able to lower their doses of corticosteroids.

Myopathy associated with anti–signal recognition peptide (anti-SRP) autoantibody is a severe, necrotizing, immune-mediated disease characterized by rapidly progressive proximal muscle weakness, myalgia, dysphagia, and markedly elevated serum creatine kinase (CK) levels. Patients generally respond poorly to conventional immunosuppressive therapies such as azathioprine, methotrexate, or intravenous immunoglobulin, says Dr. Valiyil, a rheumatology fellow at Johns Hopkins University, Baltimore.

A chart review identified eight patients who had failed standard immunosuppressive therapies who were then given two doses of rituximab, an anti-CD20 monoclonal antibody. The eight patients' mean age was 37 years; six were women, and four were black.

As soon as 2 months after receiving two doses of rituximab, six of the eight patients demonstrated improved muscle strength in their hands. Prior to treatment with rituximab, the mean creatine kinase was 1,835 IU/L, which declined to a mean of 777.5 IU/L after treatment. Three patients sustained the response for 12-18 months after initial dosing.

All patients on rituximab continued on adjunctive steroid therapy but were able to reduce their corticosteroid dose. The mean highest prednisone dose prior to receiving rituximab was 75 mg/day; the mean lowest dose after rituximab was 21 mg/day.

Autoantibodies were detected and quantitated in the serum samples collected before and after rituximab treatment in five patients. Four of the five patients showed a decrease in serum anti-SRP antibodies. The substantial decrease in anti-SRP antibody levels after rituximab suggest that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy, commented Dr. Valiyil.

“It should be noted that [many] of our patients were African American and we cannot rule out the possibility that there may be more of a response in this particular group of patients,” explained Dr. Lisa Christopher-Stine, a rheumatologist at Hopkins who is the principal investigator of the study.

Dr. Valiyil and Dr. Christopher-Stine reported having no financial conflicts of interest to disclose.