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Book ; Online: Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation

Johansson, Mats W. / Roufosse, Florence E.

2018

Keywords	Medicine (General)
Size	1 electronic resource (279 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020101926
ISBN	9782889456246 ; 2889456242
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Editorial: Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation.

Roufosse, Florence E / Johansson, Mats W

Frontiers in medicine

2018 Volume 5, Page(s) 243

Language	English
Publishing date	2018-08-31
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2018.00243
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Article ; Online: Unmet needs and evidence gaps in hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis.

Wechsler, Michael E / Hellmich, Bernhard / Cid, Maria C / Jayne, David / Tian, Xinping / Baylis, Lee / Roufosse, Florence

The Journal of allergy and clinical immunology

2023 Volume 151, Issue 6, Page(s) 1415–1428

Abstract: Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been ... ...

Abstract	Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes.
MeSH term(s)	Humans ; Granulomatosis with Polyangiitis/diagnosis ; Granulomatosis with Polyangiitis/therapy ; Churg-Strauss Syndrome/diagnosis ; Churg-Strauss Syndrome/therapy ; Evidence Gaps ; Biomarkers ; Hypereosinophilic Syndrome/diagnosis ; Hypereosinophilic Syndrome/therapy
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.03.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Biologic Therapy in Rare Eosinophil-Associated Disorders: Remaining Questions and Translational Research Opportunities.

Khoury, Paneez / Roufosse, Florence / Kuang, Fei Li / Ackerman, Steven J / Akuthota, Praveen / Bochner, Bruce S / Johansson, Mats W / Mathur, Sameer K / Ogbogu, Princess U / Spencer, Lisa A / Wechsler, Michael E / Zimmermann, Nives / Klion, Amy D

Journal of leukocyte biology

2024

Abstract: Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue ... ...

Abstract	Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized, and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included: 1) clinical outcome measures, 2) minimally invasive biomarkers of disease activity, 3) predictors of response to biologic agents, and 4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiae051
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Article ; Online: Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5.

Rothenberg, Marc E / Roufosse, Florence / Faguer, Stanislas / Gleich, Gerald J / Steinfeld, Jonathan / Yancey, Steven W / Mavropoulou, Eleni / Kwon, Namhee

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 9, Page(s) 2367–2374.e3

Abstract: Background: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown.: Objective: To assess mepolizumab efficacy by baseline blood ... ...

Abstract	Background: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. Objective: To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. Methods: This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). Results: Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P = .76 and P = .90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P = .42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). Conclusions: Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Child ; Eosinophils ; Humans ; Hypereosinophilic Syndrome/drug therapy ; Interleukin-5
Chemical Substances	Antibodies, Monoclonal, Humanized ; Interleukin-5 ; mepolizumab (90Z2UF0E52)
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2022.04.037
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis.

Wechsler, Michael E / Nair, Parameswaran / Terrier, Benjamin / Walz, Bastian / Bourdin, Arnaud / Jayne, David R W / Jackson, David J / Roufosse, Florence / Börjesson Sjö, Lena / Fan, Ying / Jison, Maria / McCrae, Christopher / Necander, Sofia / Shavit, Anat / Walton, Claire / Merkel, Peter A

The New England journal of medicine

2024 Volume 390, Issue 10, Page(s) 911–921

Abstract: Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating ... ...

Abstract	Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA. Methods: We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab. Adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned in a 1:1 ratio to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks. The primary end point was remission at weeks 36 and 48 (prespecified noninferiority margin, -25 percentage points). Secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety. Results: A total of 140 patients underwent randomization (70 assigned to each group). The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], -13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab. The accrued duration of remission and the time to first relapse were similar in the two groups. Complete withdrawal of oral glucocorticoids during weeks 48 through 52 was achieved in 41% of the patients who received benralizumab and 26% of those who received mepolizumab. The mean (±SD) blood eosinophil count at baseline was 306.0±225.0 per microliter in the benralizumab group and 384.9±563.6 per microliter in the mepolizumab group, decreasing to 32.4±40.8 and 71.8±54.4 per microliter, respectively, at week 52. Adverse events were reported in 90% of the patients in the benralizumab group and 96% of those in the mepolizumab group; serious adverse events were reported in 6% and 13%, respectively. Conclusions: Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA. (Funded by AstraZeneca; MANDARA ClinicalTrials.gov number, NCT04157348.).
MeSH term(s)	Adult ; Humans ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Chronic Disease ; Churg-Strauss Syndrome/drug therapy ; Churg-Strauss Syndrome/immunology ; Glucocorticoids/adverse effects ; Glucocorticoids/therapeutic use ; Granulomatosis with Polyangiitis/drug therapy ; Granulomatosis with Polyangiitis/immunology ; Recurrence ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Double-Blind Method ; Remission Induction ; Injections, Subcutaneous ; Interleukin-5 Receptor alpha Subunit/antagonists & inhibitors ; Eosinophils/drug effects ; Eosinophils/immunology
Chemical Substances	Antibodies, Monoclonal, Humanized ; benralizumab (71492GE1FX) ; Glucocorticoids ; mepolizumab (90Z2UF0E52) ; Anti-Inflammatory Agents ; IL5RA protein, human ; Interleukin-5 Receptor alpha Subunit
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Clinical Trial, Phase III ; Comparative Study ; Equivalence Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa2311155
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Article ; Online: Editorial

Florence E. Roufosse / Mats W. Johansson

Frontiers in Medicine, Vol

Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation

2018 Volume 5

Keywords	eosinophils ; interleukin-5 ; asthma ; hypereosinophilic syndromes ; eosinophilic esophagitis ; mastocytosis ; Medicine (General) ; R5-920
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Pathogenic Advances and Therapeutic Perspectives for Eosinophilic Inflammation

Mats W. Johansson / Florence E. Roufosse

2018

Abstract: With the recent approval of the first eosinophil-depleting therapeutic agents targeting the IL-5 pathway for treatment of severe eosinophilic asthma, eosinophils and eosinophilic disorders are in the limelight. Indeed, setbacks during clinical ... ...

Abstract	With the recent approval of the first eosinophil-depleting therapeutic agents targeting the IL-5 pathway for treatment of severe eosinophilic asthma, eosinophils and eosinophilic disorders are in the limelight. Indeed, setbacks during clinical development of these compounds have revealed how much remains to be known about eosinophil biology in vivo, and have nurtured profuse research both on basic eosinophil biology and on pathogenic disease mechanisms, in order to better delineate the most meaningful targets for innovative therapeutic strategies. On one hand, variable degrees of eosinophil depletion observed in some compartments during IL-5-targeted treatment indicate that certain eosinophil subsets may not rely on this cytokine and/or that other important pro-eosinophilic mediators and signaling pathways are operative in vivo. On the other hand, it is increasingly clear that disorders involving eosinophils such as asthma are the final outcome of complex interactions between diverse cell types and mediators, beyond eosinophils and IL-5. These include type 2 helper T (Th2) cells and innate lymphoid cells, mast cells, and a variety of factors that either activate eosinophils or are released by them. Although a considerable amount of research has focused on asthma because it is a common condition and because management of severe asthma remains a major challenge, several rare eosinophilic disorders with more homogenous features have proven to be extremely useful models to reach a better understanding of the involvement of eosinophils in tissue damage and dysfunction, and of the micro-environmental interactions operating within the complex network of eosinophilic inflammation. Unraveling this interplay has resulted in advances in the development of molecular tools to detect disease subsets and to monitor therapeutic responses, and in identification of promising new therapeutic targets. This Research Topic dedicated to eosinophilic conditions covers aspects of the biology of eosinophils and closely related cells of particular relevance for drug development, reports on translational research investigating pathogenic mechanisms of specific eosinophilic disorders in humans that will likely result in significant changes in the way patients are managed, and presents an overview of the current advancement of targeted drug development for these conditions, with a special focus on asthma.
Keywords	Eosinophil Biology ; Th2 cell ; ILC2 ; Asthma ; mast cell ; Eosinophilic Esophagitis ; Hypereosinophilic Syndrome
Subject code	610
Language	English
Publisher	Frontiers Media SA
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD3

Carpentier, Caroline / Schandené, Liliane / Dewispelaere, Laurent / Heimann, Pierre / Cogan, Elie / Roufosse, Florence

The journal of allergy and clinical immunology. In practice

2021 Volume 9, Issue 6, Page(s) 2426–2439.e7

Abstract: Background: Identification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications.: Objective: This study was undertaken to assess diagnostic tools for L-HES ... ...

Abstract	Background: Identification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications. Objective: This study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations. Methods: Biomarkers of T-cell-driven disease were compared between patients with L-HES versus idiopathic HES (I-HES) variants. Those performed routinely (serum immunoglobulin levels, T-cell phenotyping, T-cell receptor [TCR] gene rearrangement patterns) were collected from medical files, whereas others were prospectively assessed on stored blood samples (serum CCL17/thymus and activation regulated chemokine [TARC] levels, in vitro cytokine production). Results: This study included 48 patients with I-HES and 20 with L-HES associated with a CD3 Conclusion: Adapting the standard of procedure for T-cell phenotyping in patients with unexplained hypereosinophilia is currently the most reliable means of identifying those with CD3
MeSH term(s)	CD3 Complex ; CD4-Positive T-Lymphocytes ; Cytokines ; Humans ; Hypereosinophilic Syndrome/diagnosis ; Hypereosinophilic Syndrome/genetics ; T-Lymphocytes
Chemical Substances	CD3 Complex ; Cytokines
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2021.01.030
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Article ; Online: Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies.

Jacobsen, Elizabeth A / Jackson, David J / Heffler, Enrico / Mathur, Sameer K / Bredenoord, Albert J / Pavord, Ian D / Akuthota, Praveen / Roufosse, Florence / Rothenberg, Marc E

Annual review of immunology

2021 Volume 39, Page(s) 719–757

Abstract: The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, ... ...

Abstract	The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.
MeSH term(s)	Animals ; Biological Therapy ; Eosinophils ; Humans ; Mice ; Mice, Knockout ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2021-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604953-9
ISSN	1545-3278 ; 0732-0582
ISSN (online)	1545-3278
ISSN	0732-0582
DOI	10.1146/annurev-immunol-093019-125918
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