Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo
- Elisangela Santos-Valente1,
- Heike Buntrock-Döpke1,2,
- Rola Abou Taam3,
- Stefania Arasi4,
- Arzu Bakirtas5,
- Jaime Lozano Blasco6,
- Klaus Bønnelykke7,
- Mihai Craiu8,
- Renato Cutrera9,
- Antonine Deschildre10,
- Basil Elnazir11,
- Louise Fleming12,13,
- Urs Frey14,
- Monika Gappa15,
- Antonio Nieto Garcia16,
- Kirsten Skamstrup Hansen7,
- Laurence Hanssens17,
- Karina Jahnz-Rozyk18,
- Milos Jesenak19,20,
- Sebastian Kerzel1,
- Matthias Kopp21,22,
- Gerard H. Koppelman23,24,
- Uros Krivec25,
- Kenneth A. MacLeod26,
- Mika Mäkelä27,
- Erik Melén28,29,
- Györgyi Mezei30,
- Alexander Moeller31,
- Andre Moreira32,33,
- Petr Pohunek34,
- Predrag Minić35,
- Niels W. P. Rutjes36,
- Patrick Sammut37,
- Nicolaus Schwerk38,39,
- Zsolt Szépfalusi40,
- Mirjana Turkalj41,
- Iren Tzotcheva42,
- Alexandru Ulmeanu43,
- Stijn Verhulst44,45,
- Paraskevi Xepapadaki46,
- Jakob Niggel47,
- Susanne Vijverberg48,
- Anke-Hilse Maitland van der Zee48,
- Uros Potocnik49,50,
- Susanne Reinartz51,
- Kees van Drunen52 and
- Michael Kabesch1,2⇑
- 1Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany
- 2Member of the Research and Development Campus Regensburg (WECARE) at the Hospital St. Hedwig of the Order of St. John, Regensburg, Germany
- 3Service de pneumologie pédiatrique, AP-HP, Hôpital Necker Enfants-Malades, Paris, France
- 4Pediatric Allergology Unit, Bambino Gesù Children's Hospital, , Rome, Italy
- 5Department of Pediatrics, Division of Pediatric Allergy and Asthma, Gazi University School of Medicine, Ankara, Turkey
- 6Department of Pediatric Allergy and Clinical Immunology, Hospital Sant Joan de Déu, Universitat de Barcelona, , Barcelona, Spain
- 7Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
- 8Respiratory Department, in the National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Bucharest, Romania
- 9Pediatric Pulmonology & Respiratory Intermediate Care Unit, Sleep and Long-Term Ventilation Unit, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, , Rome, Italy
- 10University of Lille, CHU Lille, Paediatric Pulmonology and Allergy Unit, Hôpital Jeanne de Flandre, Lille, France
- 11Children's Health Ireland (CHI) at Tallaght University Hospital, Dublin, Ireland
- 12Respiratory Paediatrics, National Heart & Lung Institute, Imperial College London, London, UK
- 13Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK
- 14University Children's Hospital Basel, University of Basel, Basel, Switzerland
- 15Evangelisches Krankenhaus Düsseldorf, Children's Hospital, Düsseldorf, Germany
- 16Pediatric Allergy and Pneumology Unit, Children's Hospital La Fe; Health Research Institute La Fe, Valencia, Spain
- 17Service de Pneumologie-Allergologie, Centre de reference de Mucoviscidose de l'ULB, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium
- 18Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, Warsaw, Poland
- 19Department of Paediatrics, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
- 20Department of Clinical Immunology and Allergology, University Teaching Hospital in Martin, Martin, Slovakia
- 21Department of Pediatric Allergy and Pulmonology, Clinic of Pediatrics UKSH, University of Luebeck, Luebeck, Germany
- 22German Center for Lung Research DZL, Airway Center North (ARCN) Lübeck and Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany
- 23Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, University of Groningen, Beatrix Children's Hospital, Groningen, the Netherlands
- 24Gronigen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- 25Department of Paediatric Pulmology, University Children's Hospital Ljubljana, University Medical Centre Ljubljana, Ljubljana, Slovenia
- 26Royal Hospital for Sick Children, Edinburgh, United Kingdom
- 27Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- 28Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm
- 29Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- 30Allergy Unit, First Department of Pediatrics, Faculty of Medicine, , Budapest, Hungary
- 31Division of Respiratory Medicine, University Children's Hospital Zurich and Childhood Research Center, Zurich, Switzerland
- 32Serviço de Imunoalergologia, Centro Hospitalar Universitário de São João, Porto, Portugal
- 33EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
- 34Pediatric Pulmonology, Pediatric Department, 2nd Faculty of Medicine, Charles University, Prague, University Hospital Motol, Prague, Czech Republic
- 35Mother and Child Health Institute of Serbia, Belgrade, Serbia
- 36Department of Paediatric Pulmonology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- 37Department of Paediatrics, Respiratory Medicine and Allergy, Mater Dei Hospital, Malta
- 38Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
- 39German Center for Lung Research, Biomedical Research in End Stage and Obstructive Lung Disease/BREATH, German Center for Lung Research, Hannover, Germany
- 40Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center Pediatrics, Medical University of Vienna, Vienna, Austria
- 41Srebrnjak Children's Hospital, Zagreb, and School of Medicine, University of Osijek “Josip Juraj Strossmayer”, Osijek, and Catholic University of Croatia, Zagreb, Croatia
- 42Pediatric Clinic, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria
- 43“Grigore Alexandrescu” Emergency Hospital for Children, Bucharest, Romania
- 44Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium
- 45Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- 46Children's Allergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, Athens, Greece
- 47Datadesk Limited, Regensburg, Germany
- 48Department of Respiratory Medicine, , University of Amsterdam, Amsterdam, the Netherlands
- 49Department of Gynaecology and Breast Oncology, University Medical Centre Maribor, Maribor, Slovenia
- 50Centre for Human Molecular Genetics and Pharmacogenomics, Medical faculty, University of Maribor, Maribor, Slovenia
- 51Department of Otorhinolaryngology, Tergooi Hospitals, Hilversum
- 52Department of Otorhinolaryngology. Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Michael Kabesch, MD, University Children's Hospital Regensburg (KUNO), At St. Hedwig ‘s Hospital of the order of St. John, Department of Pediatric Pneumology and Allergy, Steinmetzstr. 1-3, D-93049 Regensburg, Germany. E-mail: michael.kabesch{at}barmherzige-regensburg.de
Abstract
Introduction Severe asthma is a rare disease in children, for which three biologicals –anti-IgE, anti-IL-5 and anti-IL-4RA antibodies– are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe.
Methods Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data.
Results We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma and only a few restrict therapy to specialised centres. We observed significant variation in the timepoint when treatment success is assessed, in therapy duration, and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals.
Conclusion Substantial differences exist in the management of childhood severe asthma across Europe and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
Footnotes
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Conflict of interest: Dr. Santos-Valente has nothing to disclose.
Conflict of interest: Dr. Buntrock-Döpke has nothing to disclose.
Conflict of interest: Dr. Abou Taam has nothing to disclose.
Conflict of interest: Dr. Arasi has nothing to disclose.
Conflict of interest: Dr. BAKIRTAS has nothing to disclose.
Conflict of interest: Dr. Lozano Blasco reports personal fees from Novartis, personal fees from GSK, outside the submitted work;.
Conflict of interest: Dr. Bønnelykke has nothing to disclose.
Conflict of interest: M. Craiu reports a speaker fee for a scientific meeting regarding 5 years of Xolair in Romania (9 May 2018) from Novartis Romania outside the submitted work.
Conflict of interest: Dr. Cutrera has nothing to disclose.
Conflict of interest: Dr. Deschildre reports personal fees and other from Novartis, GSK, Sanofi, outside the submitted work.
Conflict of interest: Dr. Elnazir has nothing to disclose.
Conflict of interest: Dr. Fleming reports grants from Asthma UK, and speakers fees or fees for expert consultation from Teva, Astra Zeneca, Sanofi, Respiri, Novartis; all fees paid direct to her institution and outside the submitted work.
Conflict of interest: Dr. Frey has nothing to disclose.
Conflict of interest: Dr. Gappa reports personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, personal fees from Sanofi, outside the submitted work; .
Conflict of interest: Dr. NIETO GARCÍA reports and I received grants for clinical studies and advisory boards membership, as well as lecture fees from Novartis, GSK and MSD.
Conflict of interest: Dr. Skamstrup Hansen has nothing to disclose.
Conflict of interest: Dr. Hanssens has nothing to disclose.
Conflict of interest: Dr. Jahnz-Rozyk has nothing to disclose.
Conflict of interest: Dr. Jesenak has nothing to disclose.
Conflict of interest: S. Kerzel reports a speaker fee from Novartis for a lecture that has no topical overlap at all with the current manuscript.
Conflict of interest: Dr. Kopp reports personal fees from ALK-Abello GmbH, grants and personal fees from Allergopharma GmbH, personal fees from Chiesi GmbH, personal fees from Infectopharm GmbH, personal fees from Novartis GmbH, personal fees from Sanofi Aventis GmbH, personal fees from Vertex GmbH, outside the submitted work;.
Conflict of interest: Dr. Koppelman reports grants from Lung Foundation Netherlands, TETRI Foudation, Ubbo Emmius Foundation, Vertex, Teva the Netherlands, GSK, European Union, outside the submitted work; and he participated in advisory board meetings to GSK and Pure IMS (Money to institution).
Conflict of interest: Dr. Krivec has nothing to disclose.
Conflict of interest: Dr. MacLeod has nothing to disclose.
Conflict of interest: Dr. Mäkelä has nothing to disclose.
Conflict of interest: Dr. Melén reports personal fees from AstraZeneca, Chiesi, Novartis and Sanofi (Advisory board fees), outside the submitted work;.
Conflict of interest: Dr. Mezei reports non financial support from LOFARMA, outside the submitted work; travel grant.
Conflict of interest: Dr. Möller has nothing to disclose.
Conflict of interest: Dr. Moreira has nothing to disclose.
Conflict of interest: P. Pohunek reports personal fees for advisory board membership from Novartis and GlaxoSmithKline, and for consultation from Chiesi and AstraZeneca, outside the submitted work.
Conflict of interest: Dr. Minić has nothing to disclose.
Conflict of interest: Dr. Rutjes reports personal fees from GSK (Advisory board on mepolizumab), personal fees from Sanofi (Advisory board on dupilumab), outside the submitted work;.
Conflict of interest: Dr. Sammut has nothing to disclose.
Conflict of interest: N. Schwerk reports lecture and advisory board fees from Novartis, Sanofi and Allergopharma; advisory board fees from Boehringer Ingelheim; and lecture fees from Abvie and Infectopharm, all outside the submitted work.
Conflict of interest: Dr. Szépfalusi has nothing to disclose.
Conflict of interest: Dr. Turkalj has nothing to disclose.
Conflict of interest: Dr. Tzotcheva has nothing to disclose.
Conflict of interest: Dr. Ulmeanu has nothing to disclose.
Conflict of interest: Dr. Verhulst reports grants from GSK, during the conduct of the study;.
Conflict of interest: P. Xepapadaki reports personal fees for advisory services from Uriach, Novartis, Nestle and Nutricia outside the submitted work.
Conflict of interest: Jakob Niggel has nothing to disclose.
Conflict of interest: Dr. Vijverberg reports grants from ZonMW, during the conduct of the study;.
Conflict of interest: AHM has received research grants outside the submitted work from GSK, Boehringer Íngelheim and Vertex, she is the PI of a P4O2 (Precision Medicine for more Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD and Novartis), and she has served in advisory boards for AstraZeneca, GSK and Boehringer Ingelheim with money paid to her institution.
Conflict of interest: U. Potocnik was funded by the Ministry of Education, Science and Sport of the Republic of Slovenia, grant PERMEABLE (contract number C3330-19-252012), during the conduct of the study.
Conflict of interest: Dr. Reinartz has nothing to disclose.
Conflict of interest: Dr. van Drunen has nothing to disclose.
Conflict of interest:
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- Received March 4, 2021.
- Accepted April 10, 2021.
- Copyright ©The authors 2021
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