Dataset Information

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

ABSTRACT:

Background/objectives

Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment.

Methods

A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options.

Results

DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6-22.1% (clinical trials programme), 0.5-70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy.

Conclusions

Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate-severe DAOSD and high-risk patients.

SUBMITTER: Foley P

PROVIDER: S-EPMC9826507 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

Foley Peter P Kerdraon Yves A YA Hogden John P JP Shumack Stephen S Spelman Lynda L Sebaratnam Deshan F DF Su Charles S CS Katelaris Constance H CH

The Australasian journal of dermatology 20220920 4

<h4>Background/objectives</h4>Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment.<h4>Methods</h4>A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was u ...[more]

PMID: 36125089

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Project description:ObjectiveTo elucidate the pathogenesis of dupilumab (Dupixent®)-associated ocular surface disease (DAOSD).DesignProspective single-center cohort study.SubjectsTwenty patients with moderate-to-severe atopic dermatitis (AD) who received dupilumab and 10 age- and sex-matched healthy controls were enrolled in the study.MethodsThe study cohort underwent a thorough slit-lamp and entire-body dermatologic examination. Conjunctival swabs and smears were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. To analyse the ocular surface microbiome, 16S ribosomal RNA sequencing was performed, smears were hematoxylin and eosin stained, and serum cytokines were measured by using a multiplex immunobead assay.Main outcome measuresComposition of ocular surface microbiome and cellular component as well as serum cytokine levels.ResultsSix of the 20 patients with AD developed DAOSD after dupilumab initiation; these patients responded after a delay to treatment as quantified by Eczema Area and Severity Index and Investigator's Global Assessment score. Conjunctival smears showed massive neutrophilic infiltration and serum analysis revealed increased systemic levels of neutrophil-priming proinflammatory cytokines, in particular interleukin-1β and tumor necrosis factor α, in patients with DAOSD compared with those without it. The ocular surface microbiome of patients with DAOSD was characterized by a diverse and persistent microbial colonization, particularly by Acetobacter aceti. In contrast, microbial diversity decreased in patients with AD without DAOSD after the initiation of dupilumab treatment, especially the abundance of Staphylococcus aureus. In vitro experiments substantiated the potential role of the microbiome, showing increased growth of A. aceti and decreased growth of S. aureus in presence of dupilumab.ConclusionsPersistent neutrophilic infiltration and a unique microbial landscape on the ocular surface associated with elevated levels of systemic proinflammatory cytokines typify DAOSD.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Project description:BackgroundAustralian governments are increasingly mandating the use of cost-benefit analysis (CBA) to inform the efficient allocation of government resources. CBA is likely to be useful when evaluating preventive health interventions that are often cross-sectoral in nature and require Cabinet approval prior to implementation. This study outlines a CBA framework for the evaluation of preventive health interventions that balances the need for consistency with other agency guidelines whilst adhering to guidelines and conventions for health economic evaluations.MethodsWe analysed CBA and other evaluation guidance documents published by Australian federal and New South Wales (NSW) government departments. Data extraction compared the recommendations made by different agencies and the impact on the analysis of preventive health interventions. The framework specifies a reference case and sensitivity analyses based on the following considerations: (1) applied economic evaluation theory; (2) consistency between CBA across different government departments; (3) the ease of moving from a CBA to a more conventional cost-effectiveness/cost-utility analysis framework often used for health interventions; (4) the practicalities of application; and (5) the needs of end users being both Cabinet decision-makers and health policy-makers.ResultsNine documents provided CBA or relevant economic evaluation guidance. There were differences in terminology and areas of agreement and disagreement between the guidelines. Disagreement between guidelines involved (1) the community included in the societal perspective; (2) the number of options that should be appraised in ex ante analyses; (3) the appropriate time horizon for interventions with longer economic lives; (4) the theoretical basis and value of the discount rate; (5) parameter values for variables such as the value of a statistical life; and (6) the summary measure for decision-making.ConclusionsThis paper addresses some of the methodological challenges that have hindered the use of CBA in prevention by outlining a framework that is consistent with treasury department guidelines whilst considering the unique features of prevention policies. The effective use and implementation of a preventive health CBA framework is likely to require considerable investment of time and resources from state and federal government departments of health and treasury but has the potential to improve decision-making related to preventive health policies and programmes.

Dataset Information

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

Background/objectives

Methods

Results

Conclusions

Publications

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

Similar Datasets

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