Dupilumab-associated Conjunctivitis Research Articles

Evolution of dupilumab-associated conjunctivitis in patients with atopic dermatitis after switching dupilumab to tralokinumab or Janus kinase inhibitors (RESO-ADOC study).

Clinical trials and real-life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation. (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors. This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3-6 months after inclusion) and at visit 3 (corresponding to the last medical visit). After multivariate analysis, the only factors associated with a complete resolution of dupilumab-associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47-55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82-62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94-99.66) (p = 0.002). Although uncommon, severe dupilumab-associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered.

Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

Ocular Adverse Events in Patients With Atopic Dermatitis Treated With Upadacitinib: A Real-Life Experience.

Background: Dupilumab, an interleukin (IL)-4 receptor-α inhibitor that blocks IL-4 and IL-13 signaling pathways, is an effective and well-tolerated therapy for moderate-to-severe atopic dermatitis (AD). However, an increased incidence of dupilumab-associated conjunctivitis has been reported in patients treated with dupilumab. In contrast, upadacitinib, a selective Janus kinase 1 inhibitor, is reported to have lower incidence of conjunctivitis than dupilumab. Objective: The aim of this retrospective study was to investigate ocular adverse events in adult patients with moderate-to-severe AD treated with upadacitinib after discontinuing treatment with dupilumab. Methods: In total, 33 patients were examined at the start of treatment with upadacitinib after discontinuation of dupilumab, then again after 4 weeks and every 12 weeks up to a maximum of 72 weeks. Results: Among the patients in the study, 14 had developed dupilumab-associated conjunctivitis during dupilumab treatment and had complete resolution of ocular symptoms after the switch to upadacitinib within the 1-month follow-up visit. In addition, only 1 patient treated with upadacitinib developed an episode of conjunctivitis. This condition was of mild severity and it spontaneously resolved quickly. Interestingly, this patient had no history of dupilumab-associated conjunctivitis. Conclusions: All patients who developed dupilumab-associated conjunctivitis experienced complete remission on upadacitinib and only 3% of the patients in our sample developed conjunctivitis after the start of treatment with upadacitinib. In light of this, upadacitinib appears to be a prudent and safe treatment option for AD patients with uncontrolled ocular symptoms associated with dupilumab therapy.

Two cases of dupilumab-associated conjunctivitis with high expression of IL-8 mRNA on the ocular surface: a case report

BackgroundDupilumab-induced ocular surface disease (DIOSD) has been reported in patients with atopic dermatitis treated with dupilumab, and has been recognized as an adverse event of dupilumab. Our objective was to describe two cases of DIOSD with alterations in eotaxin-2 and interleukin (IL)-8 messenger ribonucleic acid (mRNA) expression on the ocular surface.Case presentationIn the ocular surface test, specimens were collected from the patient's ocular surface, and eotaxin-2 and IL-8 mRNA levels in the specimens were measured using real-time polymerase chain reaction. The clinical score of ocular surface findings was quantified using a 5-5-5 exacerbation grading scale for allergic conjunctivitis. The first case was of a 27-year-old man who developed DIOSD 3 months after starting treatment with dupilumab injection for atopic dermatitis. After 5 weeks of topical instillation of tacrolimus ophthalmic suspension, the clinical score of ocular surface findings improved and IL-8 and eotaxin-2 mRNA expression levels gradually decreased. The second patient was a 55-year-old man who developed DIOSD 11 weeks after the start of treatment with dupilumab injection for atopic dermatitis. Four weeks after starting ophthalmological treatment with tacrolimus ophthalmic suspension, his clinical scores on ocular surface findings improved and IL-8 mRNA expression levels decreased. The ocular surface test in this case revealed increased expression levels of IL-8 mRNA on the ocular surface at the onset of DIOSD, which decreased with the improvement of objective findings.ConclusionsDIOSD, which has been successfully treated with tacrolimus ophthalmic suspension, may involve IL-8-related inflammation in addition to type 2 inflammation.

The clinical significance of dupilumab-induced blood eosinophil elevation in Japanese patients with atopic dermatitis.

This study aims to clarify the clinical significance of dupilumab-induced elevation of blood eosinophil in Japanese patients with atopic dermatitis (AD). Eosinophil elevation was defined as ≥ 5% increase of eosinophil percentage within one year after dupilumab initiation. Seven patients (15.7%) were shown to have eosinophil elevation, six of whom developed dupilumab-associated conjunctivitis (DAC) and were accompanied with DAC more frequently than those without eosinophil elevation, with statistically significant difference. Eosinophil percentage resolved spontaneously in all seven patients, including the one without DAC, despite the continuation of dupilumab treatment. None of the patients with eosinophil elevation had cardiac or pulmonary complications attributable to the hypereosinophilia. The patients with eosinophil elevation were all male. Furthermore, none of four patients in whom efficacy of dupilumab was < 25% showed eosinophil elevation. Childhood onset tended to be more common in patients with the elevation of eosinophil. This study suggests that most eosinophil elevation is associated with DAC, and that the eosinophil ratio is a biomarker for DAC.

Incidence of Bacterial and Nonbacterial Conjunctivitis in Patients With Atopic Dermatitis Treated With Dupilumab: A US Multidatabase Cohort Study.

Dupilumab-associated conjunctivitis in patients with atopic dermatitis (AD) is not fully characterized. The aim of the study was to characterize the incidence of bacterial and nonbacterial conjunctivitis among patients with AD who initiated dupilumab. Pooling longitudinal claims data from 2 US databases, we identified AD patients who newly filled either dupilumab or methotrexate, mycophenolate or cyclosporine, between March 2017 and January 2020. Outcomes were conjunctivitis and its subtypes, bacterial, allergic, and keratoconjunctivitis. Patient follow-up lasted 6 months and 1:1 propensity score (PS) matching-controlled confounding. Within 6 months of treatment initiation, the incidence of conjunctivitis was 6.6% in 3744 dupilumab initiators; bacterial conjunctivitis, 1.5%; allergic conjunctivitis, 2.2%; keratoconjunctivitis, 0.8%; and conjunctivitis requiring ophthalmic medication, 2.7%. After PS matching, dupilumab doubled the risk of conjunctivitis compared with methotrexate (relative risk [RR] 2.12; 1.56-2.91), mycophenolate (RR = 2.43; 1.32-4.47), or cyclosporine (RR = 1.83; 1.05-3.20). Risk of bacterial conjunctivitis was 1.6- to 4.0-fold increased with wide confidence intervals, and allergic conjunctivitis was increased 2.7- to 7-fold. There was no increased risk of keratoconjunctivitis. Patients with comorbid asthma had a further increased risk of conjunctivitis. One in 15 patients treated with dupilumab developed conjunctivitis driven by bacterial and allergic conjunctivitis and not keratoconjunctivitis. This risk was further increased with comorbid asthma.

Transient Increase in Circulating Basophils and Eosinophils in Dupilumab-associated Conjunctivitis in Patients with Atopic Dermatitis.

Transient Increase in Circulating Basophils and Eosinophils in Dupilumab-associated Conjunctivitis in Patients with Atopic Dermatitis.

Recognition of atopic keratoconjunctivitis during treatment with dupilumab for atopic dermatitis

To the Editor: Dupilumab, a monoclonal antibody that blocks T helper type 2 cytokines,1-4 is approved for the treatment of cutaneous manifestations of atopic dermatitis. Unfortunately, dupilumab use can result in ophthalmic complications. In the inaugural phase 3 clinical trials, 14% to 19% of patients reported dupilumab-associated conjunctivitis but were not examined by an ophthalmologist.1,4 Thus, it is possible that some of these patients could have experienced a more severe form of ocular surface disease than simple reactive conjunctivitis.

One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: A single-center retrospective study

One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: A single-center retrospective study

Conjunctivitis in patients with atopic dermatitis treated with dupilumab

Atopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. Robust evidence suggests that interleukin (IL)-4 and IL-13 are key cytokines in the immunopathogenesis of AD. New emerging agents include dupilumab, a fully human monoclonal antibody directed against the IL-4 receptor a subunit that blocks both IL-4 and IL-13 signaling and has shown significant efficacy in patients with moderate-to-severe AD. Dupilumab is approved for the treatment of moderate-to-severe AD, moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, and chronic rhinosinusitis with nasal polyps. Data from phase phase 2 and 3 studies have revealed that dupilumab generally has a low rate of adverse events, although an increased incidence of mild-to-moderate conjunctivitis has been reported for dupilumab compared with placebo.The present paper reviews the data of dupilumab-associated conjunctivitis and risk factors in adults with moderate-to-severe AD and other atopic diseases in dupilumab clinical trials and addresses the characteristics and treatment options available for this clinically highly relevant condition. Additionally, it presents data from ten studies in the real-life setting with dupilumab. Dupilumab-associated conjunctivitis incidence is higher in AD, although most cases are mild-to-moderate and have good response to topical treatment, with no need to suspend dupilumab therapy.

A Clinician's Guide to the Recognition and Management of Dupilumab-Associated Conjunctivitis.

Dupilumab, a monoclonal antibody that inhibits both interleukin (IL)-4 and IL-13 signaling, is an effective treatment option in moderate-to-severe atopic dermatitis (AD). Patients with AD are already at increased risk of developing conjunctivitis, and clinical trials and case reports have shown a greater incidence of conjunctivitis in individuals with AD treated with dupilumab. As this is one of the more commonly reported side effects of this biologic agent, it is important that clinicians are aware of this association and advise patients receiving dupilumab to report signs of conjunctivitis. This review summarizes the risk factors, clinical features, and management options for patients with AD presenting with conjunctivitis after receiving dupilumab therapy.

Dupilumab after the 2017 approval for the treatment of atopic dermatitis: what's new and what's next?

The IL-4/13 antagonist dupilumab was approved in 2017 as the first biologic for atopic dermatitis. Here, we comprehensively review compelling new data regarding dupilumab published following the approval. Daily clinical practice reports of dupilumab in atopic dermatitis are favorable and in line with the registration trials. Dupilumab does not appear to negatively affect pharmacokinetics of CYP450-metabolized drugs nor vaccination responses. Type 2 inflammation biomarkers in skin and serum are reduced following dupilumab treatment. Dupilumab increases the risk for conjunctivitis, especially with higher baseline atopic dermatitis severity and a history of conjunctivitis, but the underlying mechanisms are unknown. Favorable effects of dupilumab have been reported in treatment-recalcitrant hand eczema and prurigo nodularis cases; for allergic contact dermatitis and alopecia areata, there are conflicting responses to dupilumab, possible stemming from pathophysiological heterogeneity. Daily practice data support the continued use of dupilumab for atopic dermatitis. The only safety signal is an increased risk for conjunctivitis; mechanistic studies into dupilumab-associated conjunctivitis should lead to risk mitigation strategies. Prospective, controlled evaluations are needed for dupilumab in hand eczema and prurigo nodularis. A precision medicine-driven drug-development approach is essential to assess dupilumab for diseases with heterogeneous pathophysiologies, such as alopecia areata and allergic contact dermatitis.

Cyclosporine 0.1% (Ikervis®) treatment in steroid-dependent dupilumab-associated conjunctivitis

Dupilumab is a drug that has recently been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for the treatment of moderate-to-severe atopic dermatitis in adults. An increase in frequency of conjunctivitis related to dupilumab treatment has been reported in recent publications and clinical trials. We report two steroid-dependent cases satisfactorily treated with cyclosporine 0.1% (Ikervis ® ). To our knowledge there are no reported cases of dupilumab-associated conjunctivitis treated with cyclosporine 0.1% (Ikervis ® ). El dupilumab es un fármaco de reciente aprobación por la Food and Drug Administration (FDA) y la European Medical Agency (EMA) para el tratamiento de la dermatitis atópica moderada-severa en adultos. El incremento de la frecuencia de conjuntivitis asociadas a dupilumab ha sido expuesto en publicaciones y ensayos recientes. Presentamos 2 casos de conjuntivitis corticodependiente tratados satisfactoriamente con ciclosporina al 0,1% (Ikervis ® ). No hay casos previos descritos de conjuntivitis asociada a dupilumab tratados con ciclosporina al 0,1% (Ikervis ® ).

Tratamiento con ciclosporina al 0,1% (Ikervis®) en conjuntivitis corticodependiente asociada a dupilumab

Dupilumab is a drug that has recently been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for the treatment of moderate-to-severe atopic dermatitis in adults. An increase in frequency of conjunctivitis related to dupilumab treatment has been reported in recent publications and clinical trials. We report two steroid-dependent cases satisfactorily treated with cyclosporine 0.1% (Ikervis®). To our knowledge there are no reported cases of dupilumab-associated conjunctivitis treated with cyclosporine 0.1% (Ikervis®).

Management of dupilumab-associated conjunctivitis in atopic dermatitis.

Since September 2017, the monoclonal antibody dupilumab (Dupixent® ) has been approved in the EU for the treatment of moderate-to-severe atopic dermatitis. By blocking IL-4 and IL-13 signaling pathways, dupilumab improves both objective signs and subjective symptoms of the disease. Blocking of the IL-4aRα subunit leads to improvement of the skin's barrier function and reduction in Th2-mediated inflammation. While the rate of adverse events on dupilumab is generally low, mild-to-moderate conjunctivitis associated with redness as well as a burning and foreign body sensation has been reported in up to 28% of patients. Treatment options include topical corticosteroids and topical calcineurin inhibitors. The present review highlights the clinical presentation of dupilumab-associated conjunctivitis and addresses pharmacological and non-pharmacological options available for the treatment of this clinically highly relevant condition.

Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.