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Arthritis Res Ther. 2018 Dec 27;20(1):285. doi: 10.1186/s13075-018-1780-z.

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.

Author information

1
Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, Lundlaan, 6 PO box 85090, Utrecht, The Netherlands.
2
IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy.
3
Asklepios Clinic Sankt Augustin, Arnold-Janssen strasse 29, Sankt Augustin, Germany.
4
Department of Pediatric and Adolescents medicine, Medical faculty, University Hospital of Cologne, Kerpener Str. 62, Cologne, Germany.
5
Karolinska University Hospital, Pediatric Rheumatology Unit, Stockholm, Sweden.
6
Unité Romande d'Immuno-Rhumatologie Pediatrique/Centre Hospitalier Universitaire Vaudois (CHUV), Pediatrie, University of Lausanne, Av Bugnon 46, Lausanne, Switzerland.
7
University Hospital of Geneva, Geneva, Switzerland.
8
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.
9
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.
10
Vilnius University, Clinic of Children's Diseases, Vilnius, Lithuania and Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Santariskiu, 4, Vilnius, Lithuania.
11
Université Paris-Descartes, Institut IMAGINE, Centre de référence national pour les Rhumatismes inflammatoires et les maladies Auto-Immunes Systémiques rares de l'Enfant (RAISE), Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 149 Rue De Sevres, Paris, France.
12
Hospital Sant Joan de Déu, Universitat de Barcelona, Unidad de Reumatología Pediátrica, Esplugues de Llobregat, Passeig Sant Joan de Deu 2, Barcelona, Spain.
13
Juliane Marie Centret, Rigshospitalet, Paediatric Rheumatology Unit, Blegdamsvej 9, Copenhagen, Denmark.
14
Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza S. Onofrio, 4, Rome, Italy.
15
Sophia Children's Hospital, Department of Paediatric Rheumatology, Erasmus University Medical Centre, Dr Molewaterplein 60, Rotterdam, The Netherlands.
16
Department of Rheumatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
17
Riga Stradins University, Department of Pediatrics, Children University Hospital, Vienibas gatve 45, Riga, LV, Latvia.
18
Hippokration General Hospital, First Department of pediatrics, Thessaloniki University School of Medicine, Konstantinoupoleos 49, Thessaloniki, Greece.
19
Alexandru Ioan Cuza University of Iasi, V. Lupu str.nr. 62, Iasi, Romania.
20
Aghia Sophia Childrens Hospital, First Department of Pediatrics, University of Athens Medical School, Thivon 1, Athens, Greece.
21
German Rheumatism Research Centre, Berlin, Germany.
22
Charité University Medicine, Charitéplatz 1, Berlin, Germany.
23
Hamburg Centre for Pediatric and Adolescent Rheumatology, Dehnhaide 120, Hamburg, Germany.
24
German Center for Pediatric and Adolescent Rheumatology, Deutsches Zentrum für Kinder- und Jugendrheumatologie, Zentrum für Schmerztherapie junger Menschen, Gehfeldstrasse 24, Garmisch-Partenkirchen, Germany.
25
IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, via Gaslini 5, Genoa, Italy.
26
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genoa, Italy.
27
IRCCS Istituto Giannina Gaslini, Servizio di Epidemiologia e Biostatistica, via Gaslini 5, Genoa, Italy.
28
IRCCS Istituto Giannina Gaslini, Direzione Scientifica, via Gaslini 5, Genoa, Italy.
29
IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Via Gaslini, 5, 16147, Genoa, Italy. nicolaruperto@gaslini.org.

Abstract

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 ).

KEYWORDS:

Adverse events; Biologics; Juvenile idiopathic arthritis; Methotrexate; Registry; Safety

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