Work

Co-Occurrence Patterns of Symptom and Functional Burden Associated with Tofacitinib and Upadacitinib: A Multidimensional Analysis of Spontaneous Reports in Rheumatoid Arthritis

Year: 2026

Type: article

Abstract: Background/Objectives: Pharmacovigilance studies typically evaluate adverse events as isolated drug–event pairs, potentially overlooking symptoms and functional impairments reported concurrently within the same case. We investigated co-reported adverse event patterns for tofacitinib and upadacitinib in patients with rheumatoid arthritis (RA). Methods: FAERS reports submitted between 2004 and 2025 were included if tofacitinib or upadacitinib was recorded as the primary suspect drug for RA. Disproportionality analysis was integrated with three co-occurrence network approaches, Bayesian network analysis, and time-to-onset (TTO) analysis. Methotrexate served as an indication-matched comparator. Network analyses were stratified by reporter and submission type, and TTO was reassessed for the common 2019–2025 period. FAERS signals were also compared descriptively with Canada Vigilance data. Results: We identified 57,438 tofacitinib-related and 29,869 upadacitinib-related reports, yielding 316 and 413 positive Preferred Term signals, respectively. In the tofacitinib networks, fatigue was consistently associated with pain, mood-related terms, treatment experience, and gastrointestinal and infectious events. Upadacitinib reports exhibited a distinct pattern, with falls, pain, functional limitations, and injuries occupying central positions. Reduced grip strength, decreased joint range of motion, and loss of personal independence formed a recurrent functional cluster. Methotrexate networks were primarily organized around disease-activity terms. The median reported TTO was 34 days for tofacitinib and 115 days for upadacitinib; corresponding values for the 2019–2025 period were 59 and 115 days, respectively. These intervals should not be interpreted as true onset latency or as established hazard patterns. Conclusions: Co-reporting analysis yielded insights beyond individual disproportionality signals. Tofacitinib reports were predominantly characterized by fatigue and associated symptoms, whereas upadacitinib reports more prominently featured functional limitations, falls, and injuries.

Source: Pharmaceutics

DOI: 10.3390/pharmaceutics18101318

Authors: Jinglin Yang, Yanyan Wang, Yunfei Ma, Mengyi Lu, Fang Shao, Haichun Liu

Institutions: China Pharmaceutical University, Nanjing Medical University

Language: English

Topic: Pharmacovigilance and Adverse Drug Reactions

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499