Intravenous immunoglobulin for dermatomyositis

A Cochrane review «Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis»1 «Gordon PA, Winer JB, Hoogendijk JE et al. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database Syst Rev 2012;8:CD003643. »1 included 10 studies with a total of 258 subjects. They had either dermatomyositis and polymyositis, muscle biopsy was used in 5 trials for diagnosis. The interventions studied included the following: intravenous immunoglobulin (IVIG), plasma exchange, azathioprine, prednisolone, methotrexate, ciclosporin, infliximab, eculizumab, oral dexamethasone and etanercept, either alone or in combinations.

• Immunosuppressant vs placebo (6 studies): One study (n=15) investigating IVIG found an MD of 9.50 (95% CI 4.33 to 14.67) in improvement in muscle strength between the groups over 3 months. Another study investigating etanercept (n=16) showed that median time to treatment failure, a secondary outcome, was 148 days in the placebo vs. 358 days in the etanercept arm (p=0.0002), but no improvement in other assessed outcomes was seen.
• The other 4 RCTs assessed either plasma exchange and leukapheresis, eculizumab, infliximab or azathioprine against placebo and all produced negative results. Three of the 4 studies comparing two immunosuppressant regimes (azathioprine with methotrexate, ciclosporin with methotrexate, and intramuscular methotrexate with oral methotrexate plus azathioprine) showed no difference in efficacy between the treatment regimes. The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the median time to relapse was 44 weeks (SE 4.7) in the dexamethasone group vs. 60 (SE 2.9) in the prednisolone group (p=0.03). Immunosuppressants were associated with significant side effects.

An RCT «Aggarwal R, Charles-Schoeman C, Schessl J et al. Trial of Intravenous Immune Globulin in Dermatomyositis. N Engl J Med 2022;387(14):1264-1278. »2 including 95 adult patients with active dermatomyositis compared IVIG 2 g/kg vs. placebo over 2-5 days every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIg could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of 6 measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement.

At 16 weeks, a significantly higher percentage of patients receivin IVIG experienced at least minimal improvement in disease activity compared with placebo (79% vs. 44%; difference of 35 percentage points, 95% CI 17 to 53, p<0.001). The results for at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60) were generally in the same direction as the results of the primary end-point analysis: TIS ≥ 40 points in 68% vs. 23% (difference 45%, 95% CI 27% to 63%); TIS ≥ 60 points in 32% vs. 8% (difference 24%, 95% CI 8% to 39%). Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events (including 6 thromboembolic events) occurred.

Comment:The quality of evidence is downgraded by indirectness (only short-term outcomes reported and lack of data for patients younger than 18).