An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes.

BACKGROUND Treatment of hypereosinophilic syndrome (HES) often requires the use of immunomodulators with substantial side effect profiles. The emergence of biologics offers an alternative treatment modality. OBJECTIVE To examine real world practice data to describe the safety and consequences of various biologics suspected to either directly or indirectly impact eosinophilic inflammation for the treatment of HES. METHODS Retrospective data from 13 centers were collected via an online REDCap data repository. Inclusion criteria included 1) peripheral eosinophil count ≥1500/mm3 without a secondary cause, 2) clinical manifestations attributable to the eosinophilia, and 3) having received mepolizumab (anti-IL-5), benralizumab (afucosylated anti-IL-5 receptor alpha), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor alpha), or reslizumab (anti-IL-5) outside of a placebo-controlled clinical trial. RESULTS Of the 151 courses of biologics prescribed for 121 patients with HES, 59% resulted in improved HES symptoms and 77% enabled tapering of other HES medications. Overall, 105 patients were on daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce their glucocorticoid dose by a median reduction of 10 mg of daily prednisone equivalents. Biologics were generally safe and well tolerated other than infusion reactions with alemtuzumab. Thirteen out of 24 patients had clinical improvement after switching biologics, and 9 patients responded to increasing the dose of mepolizumab after lack of response to a lower dose. CONCLUSION Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remains to be determined. Limitations of this study include its retrospective nature and inter-site differences in data collection and availability of each biologic