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

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.

Conflict of interest statement

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.

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Figures

Fig. 1

Pharmachild graphical depiction over time of the key efficacy and safety data. Drug exposure and adverse events are represented in parallel to Juvenile Arthritis Disease Activity Score (JADAS) pattern. The Excel spreadsheet with all the data could be downloaded automatically by all participating centers. In the figure, an example of a patient from an Italian center is presented