PMID- 33104987 OWN - NLM STAT- MEDLINE DCOM- 20210126 LR - 20210126 IS - 1179-1918 (Electronic) IS - 1173-2563 (Print) IS - 1173-2563 (Linking) VI - 40 IP - 12 DP - 2020 Dec TI - Data Mining for Adverse Events of Tumor Necrosis Factor-Alpha Inhibitors in Pediatric Patients: Tree-Based Scan Statistic Analyses of Danish Nationwide Health Data. PG - 1147-1154 LID - 10.1007/s40261-020-00977-5 [doi] AB - BACKGROUND AND OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are efficacious and considered generally safe in adults. However, pediatric-specific safety evidence is scarce. The aim of this study was to screen for signals of previously unknown adverse events of TNF-alpha inhibitors in pediatric patients. METHODS: We conducted a data-mining study based on routinely collected, nationwide Danish healthcare data for 2004-2016. Using tree-based scan statistics to identify events with unexpectedly high incidence during TNF-alpha inhibitor use among patients with inflammatory bowel disease or juvenile idiopathic arthritis, two analyses were performed: comparison with episodes of no use and with other time periods from the same patient. Based on incident physician-assigned diagnosis codes from outpatient and inpatient visits in specialist care, we screened thousands of potential adverse events while adjusting for multiple testing. RESULTS: We identified 1310 episodes of new TNF-alpha inhibitor use that met the eligibility criteria. Two signals of adverse events of TNF-alpha inhibitors, as compared with no use, were detected. First, there were excess events of dermatologic complications (ICD-10: L00-L99, 87 vs. 44 events, risk difference [RD] 3.3%), which have been described previously in adults and children. Second, there were excess events of psychiatric diagnosis adjustment disorders (ICD-10: F432, 33 vs. 7 events, RD 2.0%), which was likely associated with the underlying disease and its severity, rather than with the treatment. The self-controlled analysis generated no signal. CONCLUSIONS: No signals of previously unknown adverse events of TNF-alpha inhibitors in pediatric patients were detected. The study showed that real-world data and newly developed methods for adverse events data mining can play a particularly important role in pediatrics where pre-approval drug safety data are scarce. FAU - Wintzell, Viktor AU - Wintzell V AUID- ORCID: 0000-0001-7759-0887 AD - Clinical Epidemiology Division T2, Department of Medicine Solna, Karolinska Institutet, 17176, Stockholm, Sweden. viktor.wintzell@ki.se. FAU - Svanstrom, Henrik AU - Svanstrom H AD - Clinical Epidemiology Division T2, Department of Medicine Solna, Karolinska Institutet, 17176, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Melbye, Mads AU - Melbye M AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. FAU - Ludvigsson, Jonas F AU - Ludvigsson JF AD - Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. AD - Department of Pediatrics, Orebro University Hospital, Orebro University, Orebro, Sweden. AD - Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK. AD - Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. FAU - Pasternak, Bjorn AU - Pasternak B AD - Clinical Epidemiology Division T2, Department of Medicine Solna, Karolinska Institutet, 17176, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Kulldorff, Martin AU - Kulldorff M AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. LA - eng GR - 2016-01974/Vetenskapsradet/ PT - Journal Article DEP - 20201026 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 0 (Immunologic Factors) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adolescent MH - Adult MH - Arthritis, Juvenile MH - Child MH - Child, Preschool MH - Data Interpretation, Statistical MH - Data Mining/*methods MH - Denmark MH - Female MH - Humans MH - Immunologic Factors MH - Incidence MH - Inflammatory Bowel Diseases/*drug therapy MH - Male MH - Pediatrics MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors PMC - PMC7701063 COIS- J.F. Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG) outside the submitted work. That study has received funding from Janssen corporation. H. Svanstrom reports consulting fees from Celgene and employment at IQVIA outside the submitted work. V. Wintzell, M. Melbye, B. Pasternak, and M. Kulldorff have no conflicts of interest to declare. EDAT- 2020/10/27 06:00 MHDA- 2021/01/27 06:00 PMCR- 2020/10/26 CRDT- 2020/10/26 17:15 PHST- 2020/10/07 00:00 [accepted] PHST- 2020/10/27 06:00 [pubmed] PHST- 2021/01/27 06:00 [medline] PHST- 2020/10/26 17:15 [entrez] PHST- 2020/10/26 00:00 [pmc-release] AID - 10.1007/s40261-020-00977-5 [pii] AID - 977 [pii] AID - 10.1007/s40261-020-00977-5 [doi] PST - ppublish SO - Clin Drug Investig. 2020 Dec;40(12):1147-1154. doi: 10.1007/s40261-020-00977-5. Epub 2020 Oct 26.