Bone and growth safety profiles of biologic and conventional DMARDs in juvenile idiopathic arthritis: a 21-year FAERS disproportionality analysis.

IF 6.3 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2026-10-06 DOI:10.1007/s10787-026-02409-w

Fatih Erdem, Nida Gürbüz

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引用次数: 0

Abstract

Background: Juvenile idiopathic arthritis (JIA) treatment relies on biologic and conventional disease-modifying anti-rheumatic drugs (b/csDMARDs), but pediatric-specific bone and growth safety remains incompletely characterized. Standard FAERS disproportionality analyses in pediatric polypharmacy may overstate signals through co-medication coding. We aimed to identify drug-specific bone-toxicity (Composite A) and growth/developmental (Composite B) signals and to test whether they survive a Primary-Suspect (PS) restriction designed to isolate reporter-attributed reactions.

Methods: Pre-specified disproportionality analysis of FAERS Individual Case Safety Reports (2004-2024); pediatric (≤ 17 years) JIA cohort, n = 13,459. Two parallel exposure definitions were applied: PS + SS (Primary or Secondary Suspect, broad) and PS-only (strict). Reporting odds ratios (ROR), proportional reporting ratios with χ², IC025 and a fixed-prior Bayesian shrinkage estimate were computed; a robust signal required multi-criteria thresholds in both tracks. The PS + SS analysis was independently reproduced in Python and R, with 100% concordance in signal classification.

Results: Of 21 drug × composite signals under broad PS + SS analysis, only 5 met the robust-signal definition after PS-only restriction: methotrexate (both composites; bone ROR 2.4, growth ROR 3.7) and infliximab (4.3), tocilizumab (2.8), and abatacept (3.4) for bone toxicity. Etanercept and adalimumab-the two highest-exposure drugs-showed no PS-only signal despite PS + SS Composite A signals. PS + SS magnitudes attenuated by a median 87% under PS-only restriction.

Conclusions: Methotrexate was the only drug with robust bone and growth signals, supporting skeletal and growth surveillance during chronic therapy; three biologics showed bone-toxicity signals. In this cohort, conventional PS + SS analysis substantially overstated signal magnitudes, supporting dual-track (PS + SS and PS-only) reporting for pediatric pharmacovigilance.

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生物和常规dmard治疗青少年特发性关节炎的骨和生长安全性：21年FAERS歧化分析。

背景：青少年特发性关节炎（JIA）的治疗依赖于生物和传统的疾病改善抗风湿药物（b/csDMARDs），但儿科特异性骨和生长安全性仍未完全确定。标准FAERS歧化分析在儿童多药可能夸大信号通过共同用药编码。我们的目的是确定药物特异性骨毒性（复合A）和生长/发育（复合B）信号，并测试它们是否能在设计用于分离报告源性反应的主要可疑（PS）限制条件下存活下来。方法：对2004-2024年FAERS个案安全报告进行预先指定的歧化分析；小儿（≤17岁）JIA队列，n = 13,459。采用了两种平行的暴露定义：PS + SS（主要或次要可疑，广泛）和PS-only（严格）。计算报告优势比（ROR）、具有χ2、IC025和固定先验贝叶斯收缩估计的比例报告比；一个鲁棒信号需要在两个轨道中使用多准则阈值。PS + SS分析在Python和R中独立重现，信号分类一致性100%。结果：在广泛PS + SS分析下的21种药物×复合信号中，只有5种在仅限PS后符合强信号定义：甲氨蝶呤（两种复合；骨ROR 2.4，生长ROR 3.7）和英夫利昔单抗（4.3），托珠单抗（2.8）和阿巴接受（3.4）的骨毒性。依那西普和阿达木单抗是两种暴露量最高的药物，尽管有PS + SS复合A信号，但没有PS-only信号。在仅PS限制下，PS + SS的幅度中位数衰减87%。结论：甲氨蝶呤是唯一具有强健骨骼和生长信号的药物，在慢性治疗期间支持骨骼和生长监测；三种生物制剂显示出骨毒性信号。在这个队列中，传统的PS + SS分析大大夸大了信号的大小，支持双轨（PS + SS和仅PS）报告儿科药物警戒。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]