A randomized, pilot trial of etanercept in dermatomyositis

Abstract

Objective: The aims of this pilot study were to assess (1) the safety and tolerability of etanercept in dermatomyositis (DM); (2) the feasibility and safety of a forced prednisone taper; and (3) outcome measures, including those recommended by the International Myositis Assessment Clinical Study (IMACS) group.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of etanercept (50mg subcutaneously weekly) for 52 weeks in DM subjects. Subjects were tapered off prednisone in a standardized schedule as tolerated over the initial 24 weeks of the study. Principal outcomes included adverse events, time from randomization to treatment failure (inability to wean off prednisone on schedule), and average prednisone dosage after week 24.

Results: Sixteen subjects were randomized, 11 to etanercept and 5 to placebo. There were no significant differences in adverse event rates between the treatment groups, although 5 etanercept-treated and 1 placebo-treated subjects developed worsening rash. All 5 subjects receiving placebo were treatment failures (median time to treatment failure 148 days). In contrast, 5 of 11 subjects in the etanercept arm were successfully weaned off prednisone; the median time to treatment failure in this group was 358 days (p = 0.0002). The median of the average prednisone dosage after week 24 was 29.2mg/day in the placebo group and 1.2mg/day in the etanercept group (p = 0.02). IMACS and other outcome measures demonstrated excellent test-retest reliability (intraclass correlation coefficients 0.79-0.99). There was no significant treatment effect on functional outcome.

Interpretation: The findings of no major safety concerns and a steroid-sparing effect in our study suggest that further investigation of etanercept as a treatment for DM is warranted.

Trial registration: ClinicalTrials.gov NCT00282880.

Figure 1

Participant flow is shown. Sixteen subjects were randomized; 5 were new and 11 were refractory DM patients. Most of the pre-screen failures were patients with well-controlled DM (8 patients) or refractory patients on prednisone or other second line agents prior to our modifying the protocol (71 patients). The main reason eligible patients did not participate was that they or their referring physicians wanted them to first try other treatments.

Figure 2

Kaplan-Meier curves displaying the time from randomization to the first occurrence of treatment failure. There was a significant difference between the treatment groups favoring etanercept (p = 0.0002, log-rank test)

Figure 3

Means and standard errors of Physician Global Activity Assessment score (A), Patient Global Activity Assessment score (B), average Percent of Predicted Normal (C), average Manual Muscle Testing (MMT) score (D), and MYOACT-Muscle Disease Activity score (E), are plotted over time by treatment group. There were statistically significant improvements from baseline in each of these outcomes (see Table 2), but no significant differences between the treatment groups.

Figure 3

Means and standard errors of Physician Global Activity Assessment score (A), Patient Global Activity Assessment score (B), average Percent of Predicted Normal (C), average Manual Muscle Testing (MMT) score (D), and MYOACT-Muscle Disease Activity score (E), are plotted over time by treatment group. There were statistically significant improvements from baseline in each of these outcomes (see Table 2), but no significant differences between the treatment groups.

Figure 3

Means and standard errors of Physician Global Activity Assessment score (A), Patient Global Activity Assessment score (B), average Percent of Predicted Normal (C), average Manual Muscle Testing (MMT) score (D), and MYOACT-Muscle Disease Activity score (E), are plotted over time by treatment group. There were statistically significant improvements from baseline in each of these outcomes (see Table 2), but no significant differences between the treatment groups.

Figure 3

Means and standard errors of Physician Global Activity Assessment score (A), Patient Global Activity Assessment score (B), average Percent of Predicted Normal (C), average Manual Muscle Testing (MMT) score (D), and MYOACT-Muscle Disease Activity score (E), are plotted over time by treatment group. There were statistically significant improvements from baseline in each of these outcomes (see Table 2), but no significant differences between the treatment groups.

Figure 3

Means and standard errors of Physician Global Activity Assessment score (A), Patient Global Activity Assessment score (B), average Percent of Predicted Normal (C), average Manual Muscle Testing (MMT) score (D), and MYOACT-Muscle Disease Activity score (E), are plotted over time by treatment group. There were statistically significant improvements from baseline in each of these outcomes (see Table 2), but no significant differences between the treatment groups.