PMID- 31097514 OWN - NLM STAT- MEDLINE DCOM- 20201029 LR - 20201029 IS - 1399-3003 (Electronic) IS - 0903-1936 (Print) IS - 0903-1936 (Linking) VI - 53 IP - 6 DP - 2019 Jun TI - Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients. LID - 10.1183/13993003.01824-2018 [doi] LID - 1801824 AB - There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 microg versus placebo add-on therapy in patients with symptomatic asthma aged 1-17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment.Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 microg (51%), tiotropium 2.5 microg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or sex. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 microg) than with placebo, particularly during the seasonal peaks of these AEs.This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat add-on therapy in paediatric patients with symptomatic asthma. CI - Copyright (c)ERS 2019. FAU - Vogelberg, Christian AU - Vogelberg C AD - Dept of Pediatric Pulmonology and Allergy, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany christian.vogelberg@uniklinikum-dresden.de. FAU - Szefler, Stanley J AU - Szefler SJ AD - Children's Hospital of Colorado and the University of Colorado Denver School of Medicine, Aurora, CO, USA. FAU - Vrijlandt, Elianne J L E AU - Vrijlandt EJLE AD - Dept of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Boner, Attilio L AU - Boner AL AD - UOC di Pediatria, Dipartimento di Scienze Chirurgiche Odontostomatologiche e Materno Infantili, Policlinico "G. Rossi", Verona, Italy. FAU - Engel, Michael AU - Engel M AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - El Azzi, Georges AU - El Azzi G AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Vulcu, Sebastian Dan AU - Vulcu SD AD - Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. FAU - Moroni-Zentgraf, Petra M AU - Moroni-Zentgraf PM AD - Boehringer Ingelheim Pty Ltd, Sydney, Australia. FAU - Eickmeier, Olaf AU - Eickmeier O AD - Dept of Pediatric Allergology, Pulmonology and Cystic Fibrosis, University Children's Hospital, Goethe University, Frankfurt, Germany. FAU - Hamelmann, Eckard H AU - Hamelmann EH AD - Klinik fur Kinder- und Jugendmedizin, Evangelisches Klinikum Bethel, Bielefeld and Allergy Center of the Ruhr University, Bochum, Germany. LA - eng PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190613 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Bronchodilator Agents) RN - 0 (Cholinergic Antagonists) RN - XX112XZP0J (Tiotropium Bromide) SB - IM MH - Administration, Inhalation MH - Adolescent MH - Adrenal Cortex Hormones/*administration & dosage/adverse effects MH - Asthma/*drug therapy MH - Bronchodilator Agents/administration & dosage/adverse effects MH - Child MH - Child, Preschool MH - Cholinergic Antagonists/administration & dosage/adverse effects MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Forced Expiratory Volume/drug effects MH - Humans MH - Infant MH - Male MH - Nebulizers and Vaporizers/*standards MH - Seasons MH - Tiotropium Bromide/*administration & dosage/adverse effects MH - Treatment Outcome PMC - PMC6581158 COIS- Conflict of interest: C. Vogelberg reports study-related institutional payments from Boehringer Ingelheim, during the conduct of the study; personal fees for advisory board work and lecturing from Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: S.J. Szefler reports institutional funds for consultancy from Boehringer Ingelheim, Aerocrine, Novartis, Daiichi Sankyo and Roche, institutional funds for manuscript preparation and advisory board work from Genentech, research grants and institutional funds for meeting attendance and advisory board work from GlaxoSmithKline, institutional funds for educational activities from AstraZeneca, institutional funds for advisory board work from Teva, outside the submitted work. Conflict of interest: E.J.L.E. Vrijlandt has nothing to disclose. Conflict of interest: A.L. Boner has nothing to disclose. Conflict of interest: M. Engel is an employee of Boehringer Ingelheim. Conflict of interest: G. El Azzi was employed by Boehringer Ingelheim, during the conduct of the study. Conflict of interest: S.D. Vulcu is an employee of Boehringer Ingelheim. Conflict of interest: P.M. Moroni-Zentgraf is an employee of Boehringer Ingelheim. Conflict of interest: O. Eickmeier reports compensation for conducting the study from Boehringer Ingelheim International GmbH. Conflict of interest: E. Hamelmann has consulted for Allergopharma, ALK, Bencard, Boehringer Ingelheim, GlaxoSmithKline, HAL Allergy, Novartis, Nutricia, and Stallergenes; he has received research support from the German Society of Research, the State Ministry of Education and Research of Nordrhein-Westfalen, and the German Ministry of Education and Research. EDAT- 2019/05/18 06:00 MHDA- 2020/10/30 06:00 PMCR- 2019/06/18 CRDT- 2019/05/18 06:00 PHST- 2018/09/26 00:00 [received] PHST- 2019/03/19 00:00 [accepted] PHST- 2019/05/18 06:00 [pubmed] PHST- 2020/10/30 06:00 [medline] PHST- 2019/05/18 06:00 [entrez] PHST- 2019/06/18 00:00 [pmc-release] AID - 13993003.01824-2018 [pii] AID - ERJ-01824-2018 [pii] AID - 10.1183/13993003.01824-2018 [doi] PST - epublish SO - Eur Respir J. 2019 Jun 13;53(6):1801824. doi: 10.1183/13993003.01824-2018. Print 2019 Jun.