Therapeutic Advances in Myositis
Several studies have shown the increased presence of tumor necrosis factor (TNF)-[alpha] and its soluble receptors in the muscle tissue of patients with inflammatory myopathies prompting the use of TNF-inhibitors in IIM. Early results of uncontrolled case series were promising, but the unpublished results of an NIH-sponsored randomized controlled trial of infliximab and a separate pilot study of infliximab in 13 patients with refractory myositis were less encouraging. Another recent study failed to show a consistent response to infliximab combined with weekly MTX in drug-naive patients. Five patients with active dermatomyositis treated with etanercepthad no response, but later improved after MTX or azathioprine. However, a recently published randomized double blind placebo-controlled trial of etanercept in dermatomyositis patients showed promise that etanercept is both well tolerated and efficacious with a significant steroid-sparing effect. This trial failed to enroll the projected number of patients and was underpowered, but 16 patients were randomized to receive either etanercept (n = 11, three new dermatomyositis/eight refractory) or placebo (n = 5, two new dermatomyositis/three refractory). Over 1 year, using a standardized prednisone tapering schedule, etanercept-treated patients had a significantly longer time to treatment failure (median 358 days, 6/11 failure) as compared with placebo (median 148 days, five out of five failure; P < 0.001). Etanercept also showed a steroid-sparing effect (mean prednisone dose in the etanercept-treated group after week 24 was 1.2 vs. 29.2 mg/day; P = 0.02). A repeated measure analysis over 52 weeks showed significant improvement with etanercept in many of the IMACS core-set measures including the manual muscle testing, physician global and Health Assessment Questionnaire, but significant differences were not seen in cutaneous disease activity and IMACS definition of improvement between the two groups. There were no major safety concerns and further investigation seems warranted. Interest in TNF inhibitors for the treatment of myositis may be hindered by recent reports of patients developing other autoimmune disease including polymyositis/dermatomyositis after treatment with these agents.
Anti-TNF Agents
Several studies have shown the increased presence of tumor necrosis factor (TNF)-[alpha] and its soluble receptors in the muscle tissue of patients with inflammatory myopathies prompting the use of TNF-inhibitors in IIM. Early results of uncontrolled case series were promising, but the unpublished results of an NIH-sponsored randomized controlled trial of infliximab and a separate pilot study of infliximab in 13 patients with refractory myositis were less encouraging. Another recent study failed to show a consistent response to infliximab combined with weekly MTX in drug-naive patients. Five patients with active dermatomyositis treated with etanercepthad no response, but later improved after MTX or azathioprine. However, a recently published randomized double blind placebo-controlled trial of etanercept in dermatomyositis patients showed promise that etanercept is both well tolerated and efficacious with a significant steroid-sparing effect. This trial failed to enroll the projected number of patients and was underpowered, but 16 patients were randomized to receive either etanercept (n = 11, three new dermatomyositis/eight refractory) or placebo (n = 5, two new dermatomyositis/three refractory). Over 1 year, using a standardized prednisone tapering schedule, etanercept-treated patients had a significantly longer time to treatment failure (median 358 days, 6/11 failure) as compared with placebo (median 148 days, five out of five failure; P < 0.001). Etanercept also showed a steroid-sparing effect (mean prednisone dose in the etanercept-treated group after week 24 was 1.2 vs. 29.2 mg/day; P = 0.02). A repeated measure analysis over 52 weeks showed significant improvement with etanercept in many of the IMACS core-set measures including the manual muscle testing, physician global and Health Assessment Questionnaire, but significant differences were not seen in cutaneous disease activity and IMACS definition of improvement between the two groups. There were no major safety concerns and further investigation seems warranted. Interest in TNF inhibitors for the treatment of myositis may be hindered by recent reports of patients developing other autoimmune disease including polymyositis/dermatomyositis after treatment with these agents.
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