Successful Combination of Systemic Agents for the Treatment of Atopic Dermatitis Resistant to Dupilumab Therapy

Dermatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Niccolò Gori ◽  
Andrea Chiricozzi ◽  
Dalma Malvaso ◽  
Dario Francesco D’Urso ◽  
Giacomo Caldarola ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Real Life ◽  
Signs And Symptoms ◽  
Severe Atopic Dermatitis ◽  
Inadequate Response ◽  
Conventional Drug ◽  
Systemic Agents

<b><i>Background:</i></b> Dupilumab, a monoclonal antibody inhibiting the signaling pathway of IL-4/IL-13, was shown to be safe and effective in the treatment of moderate/severe atopic dermatitis (AD) in several clinical trials and real-life experiences, with only a small percentage of patients showing to be resistant or to lose disease control. <b><i>Objectives:</i></b> In this study, we investigated the effectiveness and safety in combining dupilumab with systemic agents or phototherapy in patients experiencing an inadequate response to dupilumab. <b><i>Methods:</i></b> This retrospective, monocentric, observational study consecutively included patients aged &#x3e;18 years, with moderate-severe AD, under treatment with dupilumab. In this cohort of patients, we analyzed data of subjects who experienced an inadequate response to dupilumab, even when combined with topical corticosteroids, and for whom an additional systemic treatment or phototherapy was combined to dupilumab. <b><i>Results:</i></b> In this study, we included a total population of 69 patients treated with dupilumab. In 12/69 patients (17.4%) showing an inadequate response to dupilumab, a combined treatment consisting of dupilumab plus methylprednisolone (<i>n</i> = 5), cyclosporine (<i>n</i> = 4), methotrexate (<i>n</i> = 2), or narrow band-UVB (<i>n</i> = 1) was administered. Overall, after 8 weeks of combined therapy, the majority of patients (11 of 12) obtained an improvement of signs and symptoms of AD. Patients treated with combined therapy did not experience any adverse events, neither did they withdraw treatment because of the occurrence of adverse events. <b><i>Conclusions:</i></b> This study suggests that the combination of dupilumab with a conventional drug or phototherapy may represent a valid therapeutic choice, maintaining a good safety profile in AD patients recalcitrant to dupilumab monotherapy.

scholarly journals Update on Atopic Dermatitis

2019 ◽  
Vol 32 (9) ◽  
pp. 606 ◽  
Author(s):  
Tiago Torres ◽  
Eduarda Osório Ferreira ◽  
Margarida Gonçalo ◽  
Pedro Mendes-Bastos ◽  
Manuela Selores ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Clinical Manifestations ◽  
Skin Barrier ◽  
Future Research ◽  
Severe Atopic Dermatitis ◽  
Inadequate Response ◽  
Barrier Dysfunction ◽  
Therapeutic Goals ◽  
Global Health Issue

With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.

scholarly journals Clinical Response and Quality of Life in Patients with Severe Atopic Dermatitis Treated with Dupilumab: A Single-Center Real-Life Experience

2020 ◽  
Vol 9 (3) ◽  
pp. 791 ◽  
Author(s):  
Silvia Ferrucci ◽  
Giovanni Casazza ◽  
Luisa Angileri ◽  
Simona Tavecchio ◽  
Francesca Germiniasi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Rating Scale ◽  
Real Life ◽  
Life Quality ◽  
Depression Scale ◽  
Interleukin 4 ◽  
Severe Atopic Dermatitis ◽  
Single Center

Dupilumab is an anti-interleukin-4 receptor monoclonal antibody that was recently approved for the treatment of atopic dermatitis (AD). In this single-center retrospective study, clinical baseline data of 117 severe AD patients treated with dupilumab were collected. At baseline and at weeks 4 and 16, disease severity was assessed through the Eczema Area and Severity Index (EASI) and quality of life through the Dermatology Life Quality Index (DLQI) questionnaire, Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), Peak Pruritus Numerical Rating Scale (NRS-itch), and VAS-sleep. Response to dupilumab was defined as an improvement of ≥75% in EASI from baseline (EASI75). At multivariate analysis, AD onset before 18 years [OR, 2.9; 95% CI, 1.2–7.2; p = 0.0207] and absence of hypereosinophilia [OR, 2.24; 95% CI, 1.03–4.86; p = 0.0412] were identified as significant predictive parameters for response to dupilumab in terms of EASI75 at week 4 but not at week 16. Significant reductions in EASI, DLQI, POEM, HADS, NRS-itch, and VAS-sleep were found between week 4 versus baseline (p < 0.0001 for all) and week 16 versus baseline (p < 0.0001 for all). Early AD onset and absence of hypereosinophilia may be suggested as predictive markers of early response to dupilumab. We confirmed the efficacy and safety of this agent along with the improvement of life quality in severe AD patients.

scholarly journals Severe Atopic Dermatitis In Spain: A Real-Life Observational Study

2019 ◽  
Vol Volume 15 ◽  
pp. 1393-1401 ◽  
Author(s):  
Antoni Sicras-Mainar ◽  
Ruth Navarro-Artieda ◽  
José C Armario-Hita
Keyword(s):  
Atopic Dermatitis ◽  
Observational Study ◽  
Real Life ◽  
Severe Atopic Dermatitis

scholarly journals Participation of Neuropeptides and β-endorphin in Pathogenesis of Atopic Dermatitis. Evaluation of Levocetirizine Effectiveness upon Neuropeptides' Levels at Children with Atopic Dermatitis

2009 ◽  
Vol 7 (2) ◽  
pp. 74-80
Author(s):  
V A Revyakina ◽  
A S Agaphonov ◽  
T B Sentsova ◽  
M P Phabrika
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Symptoms ◽  
Signs And Symptoms ◽  
Severe Atopic Dermatitis ◽  
Neurokinin A ◽  
Double Blind ◽  
Developmental Mechanisms ◽  
Days Of Therapy

Objective. Determination of the role of neuropeptides and p-endorphin in developmental mechanisms of atopic dermatitis, and assessment of the effectiveness of levocetirizine, a modern Hl-antihistamine, on atopic dermatitis symptoms and its influence on the SCORAD index in children with atopic dermatitis. Materials and methods. 84 children with atopic dermatitis of moderate-to-severe or severe clinical nature, aged 1 to 17 years, were enrolled in this (double-blind or open, randomised, etc.) study. Patients were treated with levocetirizine 5 mg once daily during 14 days. The levels of P substance, neurokinin A, neurokinin B, and p-endorphin in blood serum, as well as levocetirizine effectiveness on disease symptoms and the SCORAD index were evaluated. Results. Lower neuropeptide levels were associated with disease severity; children with severe atopic dermatitis had lower neuropeptide values. Before treatment, SCORAD index in children with severe atopic dermatitis was 76,5±11,3, and after 7 days of therapy SCORAD index was 14±6,2 points (p< 0,01). By the 7th day after treatment initiation, the acute atopic dermatitis became of subacute nature and was accompanied by a regression of the cutaneous eruption in the form of significant decreasing of skin manifestations and pruritus, absence of new eruption and normalized sleep. In children with moderate-to-severe atopic dermatitis the SCORAD index before levocetirizine treatment was 44,2±3,4 points; on the 3rd day, this index was 20,4±2,6 points; and on the 7th day there was a complete absence of clinical symptoms of the main disease. Levocetirizine administration led to the disappearance of the disease clinical symptoms and pruritus in children with moderate-to-severe atopic dermatitis. Conclusion. This trial demonstrated that neuropeptides are involved in the developmental mechanisms of atopic dermatitis and that levocetirizine can significantly improve the signs and symptoms of children with moderate-to-severe or severe atopic dermatitis.

scholarly journals Experience of combined topical therapy with methylprednisoloni aceponatis and «Bepanten Plus»® in treatment of adult patients with moderate and severe atopic dermatitis

2015 ◽  
Vol 12 (6) ◽  
pp. 80-83
Author(s):  
O K Shtyrbul ◽  
O A Erina ◽  
E S Fedenko
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Combined Therapy ◽  
Topical Therapy ◽  
Adult Patients ◽  
Severe Atopic Dermatitis ◽  
Bacterial Isolation ◽  
Treatment Results ◽  
Lesional Skin ◽  
Days Of Therapy

Background. To estimate efficiency of combined therapy with methylprednisolone aceponatis and «Bepanten Plus»® in adult patients with moderate and severe atopic dermatitis. Methods. We examined 32 adult patients, who were treated with TGCS methylprednisolone aceponatis and «Bepanten Plus»®. The efficiency of therapy was estimated with index SCORAD, IGA and subjective patients assessment. For 15 of 32 patients swabs for bacterial isolation to estimate Staphylococcus aureus growth were taken from lesional skin before therapy and on the 14 th or 20 th days of treatment. Results. The аverage value of index SCORAD decreased after 15 days of therapy, Me 41,7 to Me 23,3 a point (p

Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis

2018 ◽  
Vol 54 ◽  
pp. 303-310 ◽  
Author(s):  
Zuzhen Ou ◽  
Chao Chen ◽  
Aijun Chen ◽  
Yao Yang ◽  
Weikang Zhou
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Meta Analysis ◽  
Severe Atopic Dermatitis

Clinical efficacy and safety evaluation of nimotuzumab combined with chemotherapy in the treatment of advanced colorectal cancer: A retrospective analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15009-e15009
Author(s):  
Sai-xi Bai ◽  
Ruo-rong Zhang ◽  
Wang-hua Chen ◽  
Hongmin Dong ◽  
Gang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Group ◽  
Adverse Events ◽  
Advanced Colorectal Cancer ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Objective Response ◽  
Clinical Effects ◽  
Efficacy And Safety ◽  
Significant Difference

e15009 Background: To retrospectively analyze the clinical effects and safety of nimotuzumab combined with chemotherapy as the first-line treatment of advanced colorectal cancer (ACRC). Methods: ACRC patients treated by nimotuzumab combined with chemotherapy (40 cases) or chemotherapy alone (44 cases) were enrolled in this study. Responses were evaluated by Respond Evaluation Criteria in Solid Tumors. Adverse events were evaluated by Common Terminology Criteria for Adverse Events 3.0. Results: The combined treatment group had a slightly higher objective response rate (RR) and disease control rate (DCR) (RR: 55.0% vs 36.4%; DCR: 85.0% vs 75.0%) compared to the chemotherapy alone group, although not statistically significant (P > 0.05). The median progression-free survival (PFS) was 9.89 months in the combined treatment group and 7.86 months in the chemotherapy alone group, respectively. The median survival time was 22.32 months in the combined therapy group and 18.10 months in the chemotherapy alone group, respectively (P = 0.060). There was no statistically significant difference regarding the adverse events between these two groups. Conclusions: The nimotuzumab combined with chemotherapy had similar efficacy and safety to chemotherapy-alone treatment in ACRC. The efficacy and safety of the combined treatment should be further studied with a randomized multicentre trial with a larger number of ACRC patient.

scholarly journals TAS-102 Independent and Combined Therapy in Metastatic Colorectal Cancer

2021 ◽  
Author(s):  
Cheng-Jiang Liu ◽  
Ting Hu ◽  
Ping Shao ◽  
Wu-Yang Chu ◽  
Yu Cao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Treatment Plan ◽  
Combined Therapy ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival

Abstract Objective To evaluate the effectiveness and safety of TAS-102 in the treatment of metastatic colorectal cancer. Methods The pubmed, web of science, medline, cochrane library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extract data such as median Overall Survival (mOS), median Progression-Free Survival (mPFS) and the incidence of adverse events for meta-analysis. Results Our study found that the mOS of patients treated with TAS-102 was 7.74 (95%CI: 6.09–9.85) and the mPFS was 2.91 (95%CI: 2.38–3.57). The mOS in patients treated by TAS-102 Combined with bevacizumab is 10.41 (95%CI: 8.40-12.89) and the mPFS is 4.35 (95%CI: 3.05–6.20). In the control experiment, the patients' mOS and mPFS were improved. TAS-102 + B VS. TAS- 102 (OR = 0.41, 95% CI: 0.18–0.93; OR = 0.72, 95% CI: 0.63–0.83). TAS-102 VS. Placebo(OR = 0.44, 95% CI: 0.29–0.67; OR = 0.51, 95% CI: 0.42–0.62). The incidence of adverse events in combination with bevacizumab will increase. Conclusion TAS-102 single or combined treatment can significantly improve the survival of patients, and drug safety should be considered when formulating a combined treatment plan.

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