Real-Life Experience of Tralokinumab for the Treatment of Adult Patients with Severe Atopic Dermatitis: A Multicentric Prospective Study.

BACKGROUND: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. OBJECTIVES: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort. METHODS: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. RESULTS: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. CONCLUSIONS: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis.

Strategies on long-term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab-related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6 months]) or AEs (dupilumab-related and treatment-resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician-patient shared decision. At baseline (T0) and each follow-up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment-related conjunctivitis, also with pharmacoeconomic benefit.

Ragweed pollen concentration predicts seasonal rhino-conjunctivitis and asthma severity in patients allergic to ragweed.

In this work, we investigate the correlation between ragweed pollen concentration and conjunctival, nasal, and asthma symptom severity in patients allergic to ragweed pollen using ambient pollen exposure in the Milan area during the 2014 ragweed season We calculate the pollen/symptom thresholds and we assess the effectiveness of ragweed allergen immunotherapy (AIT). A total of 66 participants allergic to ragweed (Amb a 1) were enrolled in the study and divided into two groups: AIT treated (24) and no AIT treated (42). Pollen counts and daily symptom/medication patient diaries were kept. Autoregressive distributed lag models were used to develop predictive models of daily symptoms and evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. We found significant correlations between ragweed pollen load and the intensity of symptoms for all three symptom categories, both in no AIT treated (τ = 0.341, 0.352, and 0.721; and ρ = 0.48, 0.432, and 0.881; p-value < 0.001) and in AIT treated patients ([Formula: see text]= 0.46, 0.610, and 0.66; and ρ = 0.692, 0.805, and 0.824; p-value < 0.001). In both groups, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly higher in no AIT treated than in AIT treated patients (p-value < 0.001) for all symptom categories. Pollen concentration thresholds for the four symptom severity levels (low, medium-low, medium-high and high) were calculated. Ragweed pollen concentration is predictive of symptom severity in patients with a ragweed (Amb a 1) allergy. Patients treated with AIT had significantly reduced mean symptom levels compared to those without AIT.

Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice.

BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.

Conjunctivitis associated with capecitabine treatment in a patient with colon cancer: The importance on educating patients into identifying adverse reactions.

INTRODUCTION: Conjunctivitis is an inflammation of the conjunctiva, a thin translucent mucous membrane, characterized by a dilatation of the conjunctival vessels. Causes leading to conjunctivitis are diverse, being drug related one of them. CASE REPORT: We report a case of an 80-year-old man with a diagnosis of relapsed stage IV colon cancer who developed a severe conjunctivitis, scar ectropion with lack of tissue and eversion of the subconjunctival conjunctiva after being treated with capecitabine. MANAGEMENT AND OUTCOME: Capecitabine was discontinued and pharmacological treatment was initiated with a complete resolution of the symptoms. DISCUSSION: Ocular toxicity derived from the use of systemic fluorouracil has been widely described in the literature, as well as the relationship between the use of capecitabine and the appearance of conjunctivitis. However, the development of severe conjunctivitis with other complications has not been previously reported. Monitor patients closely and perform full medication assessment should be undertaken when a patient reports visual changes to manage toxicity in the early stages. Following the patient evaluation and evolution and based on the Karch Lasanga algorithm modified by Naranjo, the adverse reaction is considered as probable.

Ocular Surface Disease in Glaucoma Patients Randomized to Benzalkonium Chloride-Containing Latanoprost and Preservative-Free Bimatoprost.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to receive BAK-containing latanoprost (Xalatan) or preservative-free bimatoprost (Lumigan PF). Intraocular pressure (IOP), basal Schirmer's test, noninvasive keratograph tear-breakup time (TBUT), conjunctival redness score (R score), OSD index (OSDI), and corneal Oxford staining were recorded and compared between the 2 groups at 1-month and 4-month visits. The influence of BAK was analyzed by a generalized estimating equation model. Results: We enrolled 74 and 76 eyes treated with latanoprost and bimatoprost, respectively. The IOP decreased in both groups, although greater reduction was observed for latanoprost (13.95 vs. 15.42 mmHg, P = 0.0264). There was a significantly negative association between tear flow and latanoprost use (ß = -0.763, P = 0.0243). The first and average TBUT did not show intergroup differences, but the area with unstable tear film increased with latanoprost use and showed marginal significance at 4-month visit (9.33% vs. 5.94% P = 0.055). In both groups, OSDI decreased, whereas Oxford stain increased over time, and R scores showed improvement after transient increase in the first month. The bimatoprost group had significantly worse conjunctival hyperemia, whereas a negative association with conjunctival hyperemia was revealed for latanoprost use (R score-bulbar nasal: ß = -0.045, P = 0.0423). Conclusions: BAK-containing latanoprost was associated with decreased tear secretion and may be associated with tear-film instability, whereas bimatoprost was associated with worse conjunctival hyperemia. Ocular surface side effects should be considered when prescribing BAK-containing medication to glaucoma patients.

Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis.

BACKGROUND: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials. OBJECTIVE: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis. METHODS: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy. RESULTS: Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%. LIMITATIONS: Limited data in terms of size and follow-up time were available. CONCLUSION: Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-Week results from the Dutch BioDay registry.

BACKGROUND: Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited. OBJECTIVE: To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis. METHODS: Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated. RESULTS: Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was -70.0% (standard deviation 33.2%) and further decreased to -76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment. LIMITATIONS: Because of the lack of a control group and observational design, factors of bias may have been induced. CONCLUSION: Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period.

Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients' records.

BACKGROUND: Clinical trial data for dupilumab, a monoclonal antibody against the interleukin-4 receptor (IL-4Rα), have shown that it is safe and effective for the treatment of moderate to severe atopic dermatitis in patients whose disease is resistant to other therapies. However, little real-world experience with dupilumab use has been reported thus far. The aim of this retrospective study was to assess overall outcomes in adult patients with atopic dermatitis (AD) treated with dupilumab. METHODS: A retrospective review of electronic medical records was conducted for patients treated with dupilumab in the Department of Dermatology at the University of California, Irvine. RESULTS: We analyzed the medical records of 77 AD patients who received dupilumab according to standard dosing and had at least one documented follow-up visit. In 66 patients (86%), dupilumab improved clinical disease severity, with 23 patients (30%) experiencing complete clearance on dupilumab. Dupilumab was generally well-tolerated and caused no serious adverse events. The most common side effects included dry eyes, conjunctivitis, and keratitis. The most common reason for discontinuation of treatment was lack of substantial clinical improvement or progression of disease severity, followed by ophthalmologic side effects. CONCLUSIONS: Overall, dupilumab was well-tolerated and resulted in clinical improvement in our patient population. These results provide additional important information on the safety and utility of dupilumab treatment for moderate to severe atopic dermatitis in the real-world clinical setting.

Treatment of refractory conjunctivitis associated to dupilumab with topical pimecrolimus applied to the eyelid skin.

Patients with atopic dermatitis commonly experience ophthalmic complications, and a higher incidence of conjunctivitis has been observed during treatment with dupilumab. We present the case of a 49-year-old woman with persistent severe atopic dermatitis who complained of refractory conjunctivitis associated with dupilumab. Ocular examination showed features of atopic conjunctivitis for which an external topical application to the eyelids of pimecrolimus 10 mg/g cream was prescribed. The patient showed substantial clinical remission after only 12 days. This case was remarkable as the medication applied externally to the eyelid skin was effective in treating the conjunctival involvement possibly due to penetration of pimecrolimus through the eyelid layers. Further studies are needed to support the use of this drug for dupilumab-related conjunctivitis.

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