Article: Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis

Wechsler, M. E., Akuthota, P., Jayne, D., Khoury, P., Langford, C. A., Merkel, P. A., Moosig, F., Specks, U., Cid, M., C., Lugmani, R., Brown, J., Mallet, S., Philipson, R., Yancey, S. W., Steinfeld, J., Weller, P. F., Gleich, G., J., & EGPA Mepolizumab Study Team. (2017). Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med; 376 (20), 1921 – 1932.

This article is a randomized control trial conducted in 31 sites across 9 countries (8 sites in the United States) that examined the efficacy of mepolizumab as an add-on therapy in patients taking 7.5 mg > x < 50 mg of prednisone to induce remission and prevent relapse compared to taking prednisone with a placebo. They also examined the possibility in prednisone dose reduction while on the mepolizumab or placebo and the safety of mepolizumab compared with the placebo.The study consisted of 136 participants (68 in each group) and followed them over the course of 52 weeks with evaluations at 24, 36, 48, and 52 weeks, as well as an 8-week follow up after cessation of the add-on therapy.

The researchers found that the patients in the treatment group had significantly higher rates of remission as per BVAS score compared to the placebo group at all assessment periods. They also found that significantly fewer patients in the mepolizumab group relapsed or had Churg-Strauss flares and that the time to first relapse was significantly longer in patients in the mepolizumab group compared to the placebo group. Furthermore, patients on mepolizumab were able to taper their prednisone doses at weeks 48 and 52 to have, on average, lower prednisode doses than the placebo group. There was no significant difference in safety (measured by incidence of adverse effects) between the two groups.

While I think this article represents one of the best pieces of literature on the topic, it does have a few limitations. First, the sample, with only 136 participants, was pretty small. This, however, is offset by the fact that Churg-Strauss Syndrome is extremely rare, so a sample of this size is significant enough not to disqualify its validity. In addition, The prednisone dose among all participants was not standardized. Moreover, the trial was conducted at many different sites in 9 different countries, including the United States. While they did not report a significant heterogeneity among the sample, this is something to consider when thinking about generalizability. Finally, the trial was partially funded by the company that produces mepolizumab. This might have resulted in some bias. However, the fact that the trial was double-blinded, this minimized the observation and reporting bias.