ORIGINAL RESEARCH article
Front. Med.
Sec. Precision Medicine
Adverse Events Related to Drug-Drug Interactions in Tocilizumab Combination Therapy: A Retrospective Analysis and Clinical Implications
Ben-nian Huo 1
Lin Shu 2
Yu Zhang 3
Nan-ge Yin 1
Huan-huan Ji 1
Yuntao Jia 1
Lin Song 1
1. Department of Pharmacy, Chongqing Key Laboratory of Child Infection and Immunity, Children 's Hospital, Chongqing Medical University, Chongqing, China
2. Department of Pharmacy, The First People's Hospital of Chongqing Liangjiang New Area, Chongqing, China
3. Department of immunology, Chongqing Key Laboratory of Child Infection and Immunity, Children 's Hospital, Chongqing Medical University, Chongqing, China
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Abstract
Objective: This study aimed to identify and evaluate the adverse events (AEs) associated with DDIs between TCZ and co-administered drugs based on real-world clinical data to offer a reference basis for clinical decision-making. Methods: A retrospective study was conducted to estimate the AEs related to DDIs between TCZ and three categories of drugs, including disease-modifying antirheumatic drugs (DMARDs), glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs). AE information for the target drugs from the first quarter of 2004 to the third quarter of 2025 was downloaded from the OpenVigil FDA data platform. The following four frequency statistical models were used to detect the AEs related to DDIs and to evaluate the correlation: the reporting ratio method, Ω shrinkage measure model, combination risk ratio model and chi-square statistics model.. Results: 824 AEs were detected by at least one of the four models. 35.6% AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone.. The most significant DDI-related AEs identified for specific TCZ drug combinations were: with DMARDs (e.g., methotrexate, hydroxychloroquine, leflunomide), focus on Anti-CCP positivity, hand deformity, and pemphigus; with glucocorticoids (specifically prednisone), monitor for pemphigus, hand deformity, glossodynia and pericarditis; with NSAIDs (specifically diclofenac), be vigilant for Anti-CCP positive, rheumatic fever, duodenal ulcer perforation and helicobacter infections. age and sex influence DDI risks: adults (≥18 years) are more susceptible to infusion reactions for TCZ +hydroxychloroquine or TCZ+ sulfasalazine, and joint swelling for TCZ+ naproxen. Male patients demonstrated a higher incidence of stomatitis for TCZ +methotrexate, and of joint swelling for TCZ+ibuprofen or TCZ+naproxen. Female patients were more susceptible to infusion-related reactions and infections for TCZ+dexamethasone, and to abdominal discomfort for TCZ+methylprednisolone. Conclusion: Healthcare providers should maintain vigilance for potential DDI-related AEs when TCZ is used in combination with DMARDs, glucocorticoids, or NSAIDs. Particular attention is suggested for signals of decreased treatment efficacy, which may be associated with the formation of anti-TCZ antibodies, and for musculoskeletal, cutaneous, and gastrointestinal events. Monitoring serological parameters (e.g., CRP, Anti-CCP), skin/mucosal symptoms, and signs of infection is recommended during combination therapy to support medication safety.
Summary
Keywords
adverse events, DMARDs, Drug drug-interaction, Glucocorticoids, NSAIDs, tocilizumab
Received
31 October 2025
Accepted
03 February 2026
Copyright
© 2026 Huo, Shu, Zhang, Yin, Ji, Jia and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lin Song
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