PMID- 30587248 OWN - NLM STAT- MEDLINE DCOM- 20191009 LR - 20200309 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 20 IP - 1 DP - 2018 Dec 27 TI - Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries. PG - 285 LID - 10.1186/s13075-018-1780-z [doi] LID - 285 AB - BACKGROUND: The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. METHODS: Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. RESULTS: Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%). CONCLUSIONS: This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA. REGISTRY REGISTRATION: The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ). FAU - Swart, Joost AU - Swart J AD - Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Lundlaan, 6 PO box 85090, Utrecht, The Netherlands. FAU - Giancane, Gabriella AU - Giancane G AD - IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy. FAU - Horneff, Gerd AU - Horneff G AD - Asklepios Clinic Sankt Augustin, Arnold-Janssen strasse 29, Sankt Augustin, Germany. AD - Department of Pediatric and Adolescents medicine, Medical faculty, University Hospital of Cologne, Kerpener Str. 62, Cologne, Germany. FAU - Magnusson, Bo AU - Magnusson B AD - Karolinska University Hospital, Pediatric Rheumatology Unit, Stockholm, Sweden. FAU - Hofer, Michael AU - Hofer M AD - Unite Romande d'Immuno-Rhumatologie Pediatrique/Centre Hospitalier Universitaire Vaudois (CHUV), Pediatrie, University of Lausanne, Av Bugnon 46, Lausanne, Switzerland. AD - University Hospital of Geneva, Geneva, Switzerland. FAU - Alexeeva, capital IE, Cyrillickaterina AU - Alexeeva capital IE, Cyrillic AD - Federal State Autonomous Institution "National Medical Research Center of Children's Health" of the Ministry of Health of the Russian Federation, LOMONOSOVSKIJ PR-T,2/62, Moscow, Russia. AD - Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia. FAU - Panaviene, Violeta AU - Panaviene V AD - Vilnius University, Clinic of Children's Diseases, Vilnius, Lithuania and Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Santariskiu, 4, Vilnius, Lithuania. FAU - Bader-Meunier, Brigitte AU - Bader-Meunier B AD - Universite Paris-Descartes, Institut IMAGINE, Centre de reference national pour les Rhumatismes inflammatoires et les maladies Auto-Immunes Systemiques rares de l'Enfant (RAISE), Unite d'Immunologie, Hematologie et Rhumatologie Pediatrique, Hopital Necker-Enfants Malades, Assistance Publique Hopitaux de Paris, 149 Rue De Sevres, Paris, France. FAU - Anton, Jordi AU - Anton J AD - Hospital Sant Joan de Deu, Universitat de Barcelona, Unidad de Reumatologia Pediatrica, Esplugues de Llobregat, Passeig Sant Joan de Deu 2, Barcelona, Spain. FAU - Nielsen, Susan AU - Nielsen S AD - Juliane Marie Centret, Rigshospitalet, Paediatric Rheumatology Unit, Blegdamsvej 9, Copenhagen, Denmark. FAU - De Benedetti, Fabrizio AU - De Benedetti F AD - Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesu, Piazza S. Onofrio, 4, Rome, Italy. FAU - Kamphuis, Sylvia AU - Kamphuis S AD - Sophia Children's Hospital, Department of Paediatric Rheumatology, Erasmus University Medical Centre, Dr Molewaterplein 60, Rotterdam, The Netherlands. AD - Department of Rheumatology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Stanevica, Valda AU - Stanevica V AD - Riga Stradins University, Department of Pediatrics, Children University Hospital, Vienibas gatve 45, Riga, LV, Latvia. FAU - Tracahana, Maria AU - Tracahana M AD - Hippokration General Hospital, First Department of pediatrics, Thessaloniki University School of Medicine, Konstantinoupoleos 49, Thessaloniki, Greece. FAU - Ailioaie, Laura Marinela AU - Ailioaie LM AD - Alexandru Ioan Cuza University of Iasi, V. Lupu str.nr. 62, Iasi, Romania. FAU - Tsitsami, Elena AU - Tsitsami E AD - Aghia Sophia Childrens Hospital, First Department of Pediatrics, University of Athens Medical School, Thivon 1, Athens, Greece. FAU - Klein, Ariane AU - Klein A AD - Asklepios Clinic Sankt Augustin, Arnold-Janssen strasse 29, Sankt Augustin, Germany. FAU - Minden, Kirsten AU - Minden K AD - German Rheumatism Research Centre, Berlin, Germany. AD - Charite University Medicine, Chariteplatz 1, Berlin, Germany. FAU - Foeldvari, Ivan AU - Foeldvari I AD - Hamburg Centre for Pediatric and Adolescent Rheumatology, Dehnhaide 120, Hamburg, Germany. FAU - Haas, Johannes Peter AU - Haas JP AD - German Center for Pediatric and Adolescent Rheumatology, Deutsches Zentrum fur Kinder- und Jugendrheumatologie, Zentrum fur Schmerztherapie junger Menschen, Gehfeldstrasse 24, Garmisch-Partenkirchen, Germany. FAU - Klotsche, Jens AU - Klotsche J AD - German Rheumatism Research Centre, Berlin, Germany. AD - Charite University Medicine, Chariteplatz 1, Berlin, Germany. FAU - Horne, Anna Carin AU - Horne AC AD - Karolinska University Hospital, Pediatric Rheumatology Unit, Stockholm, Sweden. FAU - Consolaro, Alessandro AU - Consolaro A AD - IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, via Gaslini 5, Genoa, Italy. AD - Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Universita degli Studi di Genova, Genoa, Italy. FAU - Bovis, Francesca AU - Bovis F AD - IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy. FAU - Bagnasco, Francesca AU - Bagnasco F AD - IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy. FAU - Pistorio, Angela AU - Pistorio A AD - IRCCS Istituto Giannina Gaslini, Servizio di Epidemiologia e Biostatistica, via Gaslini 5, Genoa, Italy. FAU - Martini, Alberto AU - Martini A AD - IRCCS Istituto Giannina Gaslini, Direzione Scientifica, via Gaslini 5, Genoa, Italy. FAU - Wulffraat, Nico AU - Wulffraat N AD - Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Lundlaan, 6 PO box 85090, Utrecht, The Netherlands. FAU - Ruperto, Nicolino AU - Ruperto N AUID- ORCID: 0000-0001-8407-7782 AD - IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy. nicolaruperto@gaslini.org. CN - Paediatric Rheumatology International Trials Organisation (PRINTO), BiKeR and the board of the Swedish Registry LA - eng SI - ClinicalTrials.gov/NCT01399281 PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20181227 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Antirheumatic Agents) RN - 0 (Biological Products) RN - 0 (Synthetic Drugs) RN - OP401G7OJC (Etanercept) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adolescent MH - Antirheumatic Agents/adverse effects/therapeutic use MH - Arthritis, Juvenile/diagnosis/*drug therapy MH - Biological Products/adverse effects/*therapeutic use MH - Child MH - Child, Preschool MH - Drug Monitoring MH - Etanercept/adverse effects/therapeutic use MH - Female MH - Humans MH - Male MH - Methotrexate/adverse effects/therapeutic use MH - *Pharmacovigilance MH - Prospective Studies MH - Registries/*statistics & numerical data MH - Retrospective Studies MH - Synthetic Drugs/adverse effects/*therapeutic use MH - Treatment Outcome PMC - PMC6307151 OTO - NOTNLM OT - Adverse events OT - Biologics OT - Juvenile idiopathic arthritis OT - Methotrexate OT - Registry OT - Safety COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All registries and participating centers obtained approval from their respective ethics committees and were conducted in accordance with the Declaration of Helsinki. All subjects provided written informed consent/assent based on existing national regulations. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: JS has received a research a grant from Pfizer. GH has received research funds from, has acted as a consultant for, and has participated in speaker bureaus for AbbVie, Chugai, Novartis, Pfizer Inc., and Roche. BM has acted as a principal investigator for Novartis and Enzyvant. MH has received a grant from AbbVie and a grant and personal fees from Novartis. EA has received research grants from Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, and Novartis and has received honoraria as a speaker for Roche, Novartis, and Pfizer. BB-M has participated as co-investigator to clinical trials from Pfizer, Abbott, Novartis, and Roche. JA has received grants and personal fees (consulting lecturers and speakers' bureau) and has been member of advisory groups for Pfizer, AbbVie, Roche, Sobi, Novartis, and Gebro. FDB receives consultancy/unrestricted research grants from AbbVie, Gilead, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, and UCB. VS has research collaborations with Pfizer and has received consulting fees from AbbVie and Roche. KM is funded by the German Rheumastiftung and has received research grants from Pfizer, AbbVie, and Roche and honoraria from AbbVie, Genzyme, Medac, and Pharm-Allergan. IF has received personal fees from AbbVie, Chugai, and Novartis and has acted as a consultant for Genentech, Bayer, Medac, and Lilly. AM does not have any conflict of interest to declare since March 2016, when he became the Scientific Director of the public hospital IRCCS Istituto Giannina Gaslini because this role does not allow him to render private consultancy resulting in personal income. He performed consultancy activities on behalf of the public hospital IRCCS Istituto Giannina Gaslini for AbbVie, Boehringer, Novartis, and R-Pharm and is the Scientific Director of the public hospital IRCCS Istituto Giannina Gaslini, which has received funds from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer Inc., and Sobi for the coordination activity of the PRINTO network. NW has received research grants from Pfizer and AbbVie and personal fees from Novartis. NR has acted as a consultant and has participated in speaker bureaus for AbbVie, Ablynx, Amgen, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer Inc., R-Pharm, Roche, Sanofi, Servier, and Takeda and works as a full-time public employee of the public hospital IRCCS Istituto Giannina Gaslini, which has received funds from Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer Inc., and Sobi for the coordination activity of the PRINTO network. The other authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/28 06:00 MHDA- 2019/10/11 06:00 PMCR- 2018/12/27 CRDT- 2018/12/28 06:00 PHST- 2018/05/21 00:00 [received] PHST- 2018/11/27 00:00 [accepted] PHST- 2018/12/28 06:00 [entrez] PHST- 2018/12/28 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2018/12/27 00:00 [pmc-release] AID - 10.1186/s13075-018-1780-z [pii] AID - 1780 [pii] AID - 10.1186/s13075-018-1780-z [doi] PST - epublish SO - Arthritis Res Ther. 2018 Dec 27;20(1):285. doi: 10.1186/s13075-018-1780-z.