Serum IgE reduction and paradoxical eosinophilia associated with allergic conjunctivitis after dupilumab therapy

Kimura, Akihiko; Takeda, Ayaka; Ikebukuro, Toyo; Hori, Junko

doi:10.1186/s12348-020-00234-y

Cited by 16 publications

(19 citation statements)

References 13 publications

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“…There were 13 cases of DIOSD reported in the literature, [61][62][63][64][65][66][67][68][69][70][71][72] six of which required dupilumab discontinuation due to ocular discomfort, and the symptomatology subsequently improved. In one case, however, dupilumab frequency of administration was reduced from biweekly to every 4 weeks, in this case, also, with significant ocular improvement.…”

Section: Case Reportsmentioning

confidence: 99%

“…Six patients had previous ocular disease, either dry eyes 61,72 allergic conjunctivitis, 68 trauma induced corneal flap removal, 67 keratoconus, 66 or repeated episodes of infectious conjunctivitis, keratitis, and cataract. 63 Treatment methods employed were artificial tears, 68,72 hyaluronic acid/carbomer eye drops, 73 autologous serum eyedrops, 67 corticosteroid eyedrops, 62,[64][65][66][67][68][69][70]73 cyclosporine eye drops, 64,68,72 antibiotic, 66,73 tacrolimus, 73 lifitegrast drops, 72 and surgery 63,69 (Tables 4 and 5).…”

Section: Case Reportsmentioning

confidence: 99%

See 1 more Smart Citation

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate‐to‐severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL‐4 receptor alpha subunit inhibition, thus blocking IL‐4 and IL‐13 signaling pathways. It has been shown to be an effective, well‐tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab‐induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate‐to‐severe. DIOSD was either dermatologist‐, allergist‐, or ophthalmologist‐assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.

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Section: Case Reportsmentioning

confidence: 99%

Section: Case Reportsmentioning

confidence: 99%

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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“…Sowohl in der Sinus-24-als auch in der Sinus-52-Studie verbesserten sich die sekundären Endpunkte nach der Behandlung mit Dupilumab nach 24…”

Section: Phase-iii-studien Mit Dupilumab Als Zusatztherapie Bei Crswnpunclassified

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem

Klimek

Förster‐Ruhrmann

Beule

et al. 2022

Laryngorhinootologie

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Zusammenfassung Hintergrund Die chronische Rhinosinusitis mit Nasenpolypen (CRSwNP) ist eine multifaktorielle entzündliche Erkrankung der Schleimhäute von Nase und Nasennebenhöhlen. Eine Typ-2-Inflammation als immunologischer Mechanismus wird als häufigster Endotyp beschrieben. Der Anti-IL-4-/-IL-13-Antikörper Dupilumab ist seit Oktober 2019 als Zusatztherapie zu intranasalen Glukokortikosteroiden für die Behandlung Erwachsener mit schwerer chronischer Rhinosinusitis mit Nasenpolypen zugelassen, wenn systemische Glukokortikosteroide oder eine Operation keine ausreichende Krankheitskontrolle bewirken. Während nationale und internationale Empfehlungen für den Einsatz von Dupilumab bei CRSwNP existieren, ist bislang nicht hinreichend festgelegt worden, wie diese Therapie überwacht und wann sie ggf. beendet werden sollte. Methoden In einer Literatursuche wurden die bisherigen Daten zur Behandlung der CRSwNP mit Dupilumab analysiert und die vorhandene Evidenz durch Recherchen in MEDLINE, PubMed sowie den nationalen und internationalen Studien- und Leitlinienregistern und der Cochrane Library ermittelt. Es wurden Humanstudien berücksichtigt, die im Zeitraum bis einschließlich 05/2022 publiziert wurden. Ergebnis Basierend auf der internationalen Literatur und bisherigen Erfahrungen werden von einem Expertengremium Empfehlungen für die Verlaufskontrolle, das Einhalten von Therapieintervallen und eventuelle Therapiepausen sowie eine Beendigung der Therapie bei Anwendung von Dupilumab für die Indikation CRSwNP im deutschen Gesundheitssystem auf der Grundlage eines Dokumentationsbogens gegeben. Schlussfolgerungen Das Verständnis über die immunologischen Grundlagen der CRSwNP eröffnet neue nichtoperative Therapieansätze mit Biologika für Patienten mit schweren, unkontrollierten Verlaufsformen. Wir geben hier Empfehlungen für die Verlaufskontrolle, das Einhalten von Therapieintervallen, eventuelle Therapiepausen oder eine Beendigung der Therapie bei einer Dupilumab-Behandlung als Zusatztherapie mit intranasalen Glukokortikosteroiden zur Behandlung von erwachsenen Patienten mit schwerer CRSwNP, die mit systemischen Glukokortikosteroiden und/oder chirurgischem Eingriff nicht ausreichend kontrolliert werden können.

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“…A phase 2a trial has suggested that the baseline IgE level is a good predictor of dupilumab efficacy in AA [ 45 ], and a previous study has reported high total IgE levels in patients with AA [ 46 ]. Dupilumab is considered to have paradoxical effects as a previous study has reported a case of allergic conjunctivitis with IgE reduction and hypereosinophilia after dupilumab treatment [ 47 ]. Hypereosinophilia has also been associated with alopecia in a previous study [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hypereosinophilia has also been associated with alopecia in a previous study [ 48 ]. In addition to the paradoxical effects of dupilumab on IgE and eosinophil levels [ 47 ], the long-term effects of dupilumab may vary due to AA progression and the relationship between AA and AD [ 49 ]. Moreover, the pathogenesis of alopecia is complex, and different levels of IgE and IL-4 have been reported, depending on the various types of alopecia [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Short communication: Comments on hair disorders associated with dupilumab based on VigiBase

Park

Byun

et al. 2022

PLoS ONE

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Background Dupilumab is a human antibody that blocks the signaling of both interleukin-4 and interleukin-13 receptors. It has been approved for the treatment of moderate-to-severe atopic dermatitis. However, several case reports have reported conflicting effects of dupilumab on alopecia. Objectives This study aimed to examine dupilumab-related hair disorders using the large real-world database, VigiBase. Methods All individual case safety reports associated with dupilumab in the Uppsala Monitoring Center VigiBase until December 29, 2019, were analyzed. Hair disorder-related terms were defined in High Level Terms with “alopecias,” “pilar disorders NEC (not elsewhere classified),” and “hypertrichoses,” using the Medical Dictionary for Regulatory Activities Hierarchy. Hair disorder reports associated with dupilumab and other biologics that inhibit the Th2 axis (omalizumab, mepolizumab, reslizumab, and benralizumab) were analyzed to determine their association with hair disorders. Disproportionality analysis was performed based on the proportional reporting ratio, reporting odds ratio, and information components. Results Among the 20,548 total dupilumab adverse event (AE) reports, hair disorders were reported in 462 dupilumab cases (2.2%), most of which reported hair loss, and only eight cases reported an increase in hair growth. The paradoxical trend in hair loss and growth after dupilumab use was confirmed using a disproportionality analysis. Among the other investigated biologics on Th2 immunity, only omalizumab was associated with hair loss. Additionally, hair disorders after dupilumab treatment were more frequently reported in women than in men. The proportion of hair disorder cases was high in Europe, accounting for 20.8% of hair disorder reports, whereas only 9.7% of all dupilumab-related AEs were reported in Europe. In conclusion, our analysis using a large real-world database confirmed that dupilumab is associated with hair disorders.

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Serum IgE reduction and paradoxical eosinophilia associated with allergic conjunctivitis after dupilumab therapy

Cited by 16 publications

References 13 publications

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem

Short communication: Comments on hair disorders associated with dupilumab based on VigiBase

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