Medications traditionally used for milder disease or for steroid-sparing long term, such as azathioprine and methotrexate, work in diverse inflammatory diseases, but newer approaches may not.8
An early randomized trial in EGPA, limited to patients with non-severe disease (FFS=0) who relapsed after initial induction of remission with glucocorticoids alone, suggested that azathioprine could restore and maintain remission in most cases, meaning seven of nine patients.9 Because it is difficult to conduct large trials in EGPA, other studies from the FVSG have often grouped patients with different vasculitides together based on their perceived similarity in response to immune-suppressive treatment, a controversial practice but likely essential for completing a study with sufficient statistical power to detect moderate differences.
In a recent randomized, double-blind trial from Puechal and the FVSG, EGPA (51 patients) was grouped with nonsevere microscopic polyangiitis (MPA; 25 patients) or polyarteritis nodosa (19 patients), to compare azathioprine 2 mg/kg with placebo in addition to a standard prednisone regimen.10 A combined outcome of failure to induce remission (less than 10% overall and only 2% of the EGPA subgroup) and relapse (about 40% overall, and 45% in EGPA) was used. Importantly, a relapse had to include manifestations beyond flare of asthma or rhinosinusitis. In contrast to the first study, no evidence exists that azathioprine reduced the rate of relapse. A major limitation of this study was that many relapses occurred after discontinuation of either azathioprine (12 of 19 across all three diseases) or placebo (eight of 17). Also, the EGPA group consisted of only 51 patients. Despite these limitations, it is notable the relapse rate wasn’t just “not significantly different,” but was strikingly similar. Thus, although this study does not really show that azathioprine doesn’t work in EGPA, it strongly suggests that it doesn’t work very well.
An approach aimed at the biology of eosinophils gave more promising results. Mepolizumab is a monoclonal antibody that blocks interleukin 5, an important developmental factor for eosinophils. It is FDA approved for asthma with eosinophilia at 100 mg monthly by subcutaneous injection. It has previously shown promise, at 300 mg monthly, in treating EGPA and HES in very small studies.
With that background, an industry-sponsored, double-blind, randomized trial was conducted by Wechsler et al. in 136 patients at multiple centers in Europe and the U.S.11 All patients had to have met criteria for EGPA at some point, of course, but the enrollment criteria were permissive and can be summarized as “inability to get prednisone dose below 7.5 mg without relapsing,” regardless of the reason. Patients were allowed to remain in the study if they had minor flares that required increases in prednisone. Remission was defined as absence of symptoms on no more than 4 mg prednisone and was analyzed in different ways.
