1. Secukinumab Therapy for Netherton Syndrome
- Author
-
Corinne Brunner, Barbara Meier-Schiesser, Nicole Knöpfel, Claire Barbieux, Mathilde Bonnet des Claustres, Alain Hovnanian, Davide Donghi, Agnes Schwieger-Briel, Lisa Weibel, Isabelle Luchsinger, Martin Theiler, Michael Buettcher, University of Zurich, Weibel, Lisa, Université Paris Cité, Equipe HAL, Différentiation et rôle pathogénique des lymphocytes T auxiliaires folliculaires dans la marche atopique - - Tfh-Atopy2017 - ANR-17-CE14-0025 - AAPG2017 - VALID, Développement d'une nouvelle biothérapie ciblant les mécanismes inflammatoires du syndrome de Netherton - - TARGET-NS2019 - ANR-19-CE17-0017 - AAPG2019 - VALID, University Children’s Hospital Zurich, Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Bellinzona Regional Hospital [Bellinzona], Children’s Hospital Lucerne, Partenaires INRAE, University hospital of Zurich [Zurich], Service de génétique moléculaire [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was supported by the ANR-17-CE14-0025-03 Tfh-Atopy project and ANR-19-CE17-0017-01 TARGET-NS (Drs Hovnanian and Barbieux) funded by the French National Research Agency and Imagine cross-laboratory project (Dr Bonnet des Claustres) funded by the Imagine Institute., ANR-17-CE14-0025,Tfh-Atopy,Différentiation et rôle pathogénique des lymphocytes T auxiliaires folliculaires dans la marche atopique(2017), and ANR-19-CE17-0017,TARGET-NS,Développement d'une nouvelle biothérapie ciblant les mécanismes inflammatoires du syndrome de Netherton(2019)
- Subjects
Compassionate Use Trials ,Male ,Erythema ,MESH: Interleukin-17 ,Severity of Illness Index ,MESH: Netherton Syndrome ,030207 dermatology & venereal diseases ,0302 clinical medicine ,MESH: Child ,Child ,Skin ,MESH: Compassionate Use Trials ,Interleukin-17 ,Dermatology Life Quality Index ,Phenotype ,MESH: Young Adult ,030220 oncology & carcinogenesis ,Female ,Interleukin 17 ,medicine.symptom ,Adult ,medicine.medical_specialty ,610 Medicine & health ,Dermatology ,MESH: Onychomycosis ,MESH: Phenotype ,Antibodies, Monoclonal, Humanized ,2708 Dermatology ,Young Adult ,03 medical and health sciences ,MESH: Skin ,MESH: Severity of Illness Index ,Ichthyosis linearis circumflexa ,Onychomycosis ,medicine ,Humans ,Netherton syndrome ,10220 Clinic for Surgery ,MESH: Pruritus ,Adverse effect ,MESH: Humans ,Chemokine CCL20 ,business.industry ,Pruritus ,MESH: Quality of Life ,MESH: Adult ,[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology ,MESH: Chemokine CCL20 ,medicine.disease ,MESH: Male ,MESH: Dermatologic Agents ,MESH: Antibodies, Monoclonal, Humanized ,Netherton Syndrome ,Quality of Life ,Secukinumab ,Dermatologic Agents ,business ,MESH: Female ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology ,Case series - Abstract
International audience; ImportanceNetherton syndrome (NS) is a rare, severe genetic disorder of cornification with high morbidity. Treatment for NS has been notoriously difficult. Recent studies showed an upregulated helper T cell (TH) 17/interleukin 23 (IL-23) pathway in NS, suggesting the possibility of treatment strategies that target IL-17.ObjectiveTo evaluate the clinical response of NS to treatment with the IL-17 antagonist secukinumab.Design, Setting, and ParticipantsThis case series study reports the experience of compassionate use therapy with secukinumab in 4 patients with severe NS, including 2 children, from December 1, 2018, to December 1, 2019, with 3 patients still undergoing treatment at the time of final analysis. Data were analyzed from December 1, 2018, to December 1, 2019.Main Outcomes and MeasuresExpression of IL-17 in the skin was evaluated by immunohistochemical analysis, and serum cytokine concentrations were measured using a commercially available assay. Treatment response was assessed using the Ichthyosis Area and Severity Index (IASI) total score, including measures of erythema and scaling, the Dermatology Life Quality Index (DLQI), and the 5-D itch scale.ResultsIn all 4 patients (age range, 9-27 years; 3 male and 1 female), immunostaining with an IL-17A antibody showed an increased number of positive cells in lesional skin. Cytokine assessment in serum samples revealed increased levels of CCL20. Treatment duration with secukinumab was 3 to 12 months at the time of this report. After 3 months of therapy, IASI scores were reduced by 44% to 88%, DLQI scores were reduced by 40% to 76%, and 5-D itch scale scores were reduced by 27% to 62%. This outcome was sustained at the 6-month follow-up. Two patients with an erythrodermic phenotype showed marked improvement of all parameters. A refractory palmoplantar eczematous eruption occurred in 2 patients, and a candidal nail infection developed in 2 patients. No severe adverse events were reported.Conclusions and RelevanceThis initial case series reporting the use of anti–IL-17 therapy in NS demonstrated marked cutaneous improvement, particularly in 2 pediatric patients with erythrodermic phenotypes. Further studies are needed to evaluate the long-term benefit of this potential treatment modality.
- Published
- 2020