変形性関節症における非ステロイド性抗炎症薬の有害事象評価：実世界におけるファーマコビジランス研究

Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as a critical therapeutic class for the management of osteoarthritis (OA). Nonetheless, there remains a notable deficiency in large-scale, real-world evidence regarding the safety profile of NSAIDs in individuals with OA. This study employed real-world drug monitoring methods to comprehensively assess the adverse events (AEs) reported by OA patients when using NSAIDs.

This analytical study is grounded in AEs data systematically gathered through the FDA Adverse Event Reporting System (FAERS) surveillance program. The main focus of this study is to assess the AEs reported by OA patients when using NSAIDs. The analysis encompassed a range of commonly prescribed NSAIDs, including Ibuprofen, Naproxen, Diclofenac, Celecoxib, Rofecoxib, and Piroxicam, as commonly employed in clinical settings. The study spans a 20-year observation period, from the first quarter of 2004 to the fourth quarter of 2024. An unbalanced analysis method was adopted to investigate the AEs reported with the use of NSAIDs in OA patients, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Furthermore, the study delineated the relevant system organ categories (SOC) for the identified AEs, utilizing the FAERS database. A Time-to-Onset (TTO) analysis was also conducted to systematically evaluate the temporal relationship between NSAID exposure and the onset of AEs.

In addition to the commonly observed AEs, such as gastrointestinal disturbances, renal toxicity, and cardiovascular complications, our study also reported some less common AEs during the treatment of OA with NSAIDs. It is worth noting that during the treatment of OA, reports of anemia was observed with Ibuprofen. The inappropriate antidiuretic hormone secretion and respiratory failure were reported with Naproxen in OA. The sciatica, glossodynia, lip dryness, and rheumatic fever were reported with Diclofenac in OA. The ischemic stroke, facial edema, cerebrovascular disorders, and toxic skin eruptions were reported with Celecoxib in OA. The cerebrovascular accidents and depression were reported with Rofecoxib in OA. The anemia, alveolitis, and erythema multiforme were reported with Piroxicam in OA. These AEs encompass a broad range of systemic disorders, including those affecting the blood and lymphatic system, endocrine system, respiratory, thoracic, and mediastinal systems, nervous system, musculoskeletal and connective tissues, as well as the skin, subcutaneous tissue, and psychiatric health. TTO analysis classified Diclofenac-associated gastric ulcer and Ibuprofen-associated dyspepsia as adhering to an early-failure model. All remaining drug-event combinations conformed to a random-failure model.

This study complementing evidence from clinical trials and epidemiological research, by detecting potential adverse reaction signals not fully captured or reflected in approved product information, thus providing a pharmacovigilance perspective grounded in real-world data.