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

Michael M. Chen; Florence Roufosse; Sa A. Wang; Srdan Verstovsek; Sandy R. Durrani; Marc E. Rothenberg; Thanai Pongdee; Joseph Butterfield; Timothy Lax; Michael E. Wechsler; Miguel L. Stein; Princess U. Ogbogu; Basil M. Kahwash; Sameer K. Mathur; Dagmar Simon; Praveen Akuthota; Nicole Holland; Lauren Wetzler; Jean Anne M. Ware; Canting Guo; Michael P. Fay; Paneez Khoury; Amy D. Klion; Bruce S. Bochner

doi:10.1016/j.jaip.2022.02.006

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

Michael M. Chen, Florence Roufosse, Sa A. Wang, Srdan Verstovsek, Sandy R. Durrani, Marc E. Rothenberg, Thanai Pongdee, Joseph Butterfield, Timothy Lax, Michael E. Wechsler, Miguel L. Stein, Princess U. Ogbogu, Basil M. Kahwash, Sameer K. Mathur, Dagmar Simon, Praveen Akuthota, Nicole Holland, Lauren Wetzler, Jean Anne M. Ware, Canting GuoMichael P. Fay, Paneez Khoury, Amy D. Klion, Bruce S. Bochner^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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 directly or indirectly affect eosinophilic inflammation for the treatment of HES. Methods: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm³ or greater 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 α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside 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 receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the 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 of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. Conclusions: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

Original language	English (US)
Pages (from-to)	1217-1228.e3
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/j.jaip.2022.02.006
State	Published - May 2022

Funding

This research was supported in part by the Intramural Research Program of the National Institute of Health, by National Institute of Health Grant T32AI083216 (to M.M. Chen), and by the Belgian National Fund for Scientific Research Grants F 5/4/150/5 and FC 54372 (to F. Roufosse). This research was supported in part by the Intramural Research Program of the National Institute of Health, by National Institute of Health Grant T32AI083216 (to M.M. Chen), and by the Belgian National Fund for Scientific Research Grants F 5/4/150/5 and FC 54372 (to F. Roufosse). Conflicts of interest: S.R. Durrani has received consulting fees from Allakos and Regeneron; and clinical trial support from Allakos, AstraZeneca, and Regeneron. F. Roufosse has received consulting fee from GlaxoSmithKline and AstraZeneca and royalties from UpToDate. P. Akuthota has received grants from the National Institutes of Health and the American Partnership for Eosinophilic Disorders, grants and consulting fees from GlaxoSmithKline and AstraZeneca, grants from Regeneron, consulting fees from Sanofi, and royalties from UpToDate. M.E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Bristol Myers Squibb, Astra Zeneca, Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first seven listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. M.E.R. is an inventor of patents owned by Cincinnati Children's Hospital.B.S. Bochner receives remuneration for serving on the scientific advisory board of Allakos, Inc. and owns stock in Allakos. He receives publication-related royalty payments from Elsevier and UpToDate. He is a co-inventor on existing Siglec-8?related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products. The rest of the authors declare that they have no relevant conflicts of interest.

Keywords

Biologic
Eosinophil
Eosinophilic granulomatosis with polyangiitis
Hypereosinophilic syndrome

ASJC Scopus subject areas

Immunology and Allergy

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10.1016/j.jaip.2022.02.006

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Chen, M. M., Roufosse, F., Wang, S. A., Verstovsek, S., Durrani, S. R., Rothenberg, M. E., Pongdee, T., Butterfield, J., Lax, T., Wechsler, M. E., Stein, M. L., Ogbogu, P. U., Kahwash, B. M., Mathur, S. K., Simon, D., Akuthota, P., Holland, N., Wetzler, L., Ware, J. A. M., ... Bochner, B. S. (2022). An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes. Journal of Allergy and Clinical Immunology: In Practice, 10(5), 1217-1228.e3. https://doi.org/10.1016/j.jaip.2022.02.006

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

abstract = "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 directly or indirectly affect eosinophilic inflammation for the treatment of HES. Methods: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater 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 α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside 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 receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the 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 of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. Conclusions: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.",

keywords = "Biologic, Eosinophil, Eosinophilic granulomatosis with polyangiitis, Hypereosinophilic syndrome",

author = "Chen, {Michael M.} and Florence Roufosse and Wang, {Sa A.} and Srdan Verstovsek and Durrani, {Sandy R.} and Rothenberg, {Marc E.} and Thanai Pongdee and Joseph Butterfield and Timothy Lax and Wechsler, {Michael E.} and Stein, {Miguel L.} and Ogbogu, {Princess U.} and Kahwash, {Basil M.} and Mathur, {Sameer K.} and Dagmar Simon and Praveen Akuthota and Nicole Holland and Lauren Wetzler and Ware, {Jean Anne M.} and Canting Guo and Fay, {Michael P.} and Paneez Khoury and Klion, {Amy D.} and Bochner, {Bruce S.}",

note = "Publisher Copyright: {\textcopyright} 2022 American Academy of Allergy, Asthma & Immunology",

year = "2022",

month = may,

doi = "10.1016/j.jaip.2022.02.006",

language = "English (US)",

volume = "10",

pages = "1217--1228.e3",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "Elsevier",

number = "5",

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Chen, MM, Roufosse, F, Wang, SA, Verstovsek, S, Durrani, SR, Rothenberg, ME, Pongdee, T, Butterfield, J, Lax, T, Wechsler, ME, Stein, ML, Ogbogu, PU, Kahwash, BM, Mathur, SK, Simon, D, Akuthota, P, Holland, N, Wetzler, L, Ware, JAM, Guo, C, Fay, MP, Khoury, P, Klion, AD & Bochner, BS 2022, 'An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes', Journal of Allergy and Clinical Immunology: In Practice, vol. 10, no. 5, pp. 1217-1228.e3. https://doi.org/10.1016/j.jaip.2022.02.006

TY - JOUR

T1 - An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes

AU - Chen, Michael M.

AU - Roufosse, Florence

AU - Wang, Sa A.

AU - Verstovsek, Srdan

AU - Durrani, Sandy R.

AU - Rothenberg, Marc E.

AU - Pongdee, Thanai

AU - Butterfield, Joseph

AU - Lax, Timothy

AU - Wechsler, Michael E.

AU - Stein, Miguel L.

AU - Ogbogu, Princess U.

AU - Kahwash, Basil M.

AU - Mathur, Sameer K.

AU - Simon, Dagmar

AU - Akuthota, Praveen

AU - Holland, Nicole

AU - Wetzler, Lauren

AU - Ware, Jean Anne M.

AU - Guo, Canting

AU - Fay, Michael P.

AU - Khoury, Paneez

AU - Klion, Amy D.

AU - Bochner, Bruce S.

PY - 2022/5

Y1 - 2022/5

N2 - 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 directly or indirectly affect eosinophilic inflammation for the treatment of HES. Methods: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater 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 α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside 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 receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the 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 of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. Conclusions: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

AB - 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 directly or indirectly affect eosinophilic inflammation for the treatment of HES. Methods: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater 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 α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside 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 receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the 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 of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. Conclusions: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

KW - Biologic

KW - Eosinophil

KW - Eosinophilic granulomatosis with polyangiitis

KW - Hypereosinophilic syndrome

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

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