Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system

Wu, Xiang-Ping; Lu, Xikui; Wang, Zhenting; Huang, Ling; Cai, Rongzeng; Yu, Haibin; Li, Jingyang; Xiao, Jian

doi:10.1080/14740338.2023.2223952

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…ADRs in the FAERS database are coded according to Preferred Terms (PTs) in the Medical Dictionary for Regulatory Activities Code 24.0 (MedDRA), and multiple PTs can correspond to a System Organ Class (SOC) level ( Tian et al, 2022 ; Wu et al, 2023 ). We used four algorithms to classify SOCs.We analysed SOC and PTs by four algorithms to assess the associations between drug-related ADRs and drugs.…”

Section: Methodsmentioning

confidence: 99%

Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018–2023

Lin,

Chen,

Luo

et al. 2024

Front. Pharmacol.

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Background: Tildrakizumab, the IL-23 inhibitor, is used to treat plaque psoriasis and psoriatic arthritis. Many studies have reported adverse drug reactions (ADRs) associated with Tildrakizumab.Objective: The aim of this study was to describe ADRs associated with Tildrakizumab monotherapy by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: The signals of Tildrakizumab-associated ADRs were quantified using disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms.Results: A total of 10,530,937 reports of ADRs were collected from the FAERS database, of which 1,177 reports were identified with tildrakizumab as the “primary suspect (PS)”. Tildrakizumab-induced ADRs occurred against 27 system organ classes (SOCs). A total of 32 significant disproportionality Preferred Terms (PTs) conformed to the algorithms. Unexpected significant ADRs such as coronavirus infection, herpes simplex, diverticulitis, atrial fibrillation and aortic valve incompetence were also possible. The median time to onset of Tildrakizumab-associated ADRs was 194 days (interquartile range [IQR] 84–329 days), with the majority occurring, within the first 1 and 3 months after initiation of Tildrakizumab.Conclusion: This study identified a potential signal for new ADRs with Tildrakizumab, which might provide important support for clinical monitoring and risk prediction.

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Section: Methodsmentioning

confidence: 99%

Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018–2023

Lin,

Chen,

Luo

et al. 2024

Front. Pharmacol.

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“…In certain Asian countries, peficitinib (PEF) is also used in RA clinical practice. Although there have been several randomized controlled trials (RCTs) and post-marketing surveillance, evidence on the safety of JAKis is relatively lacking compared to that on bDMARDs, owing to the shorter time since the approval of JAKis [ 1 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study

Nakayama,

Onishi,

Yamamoto

et al. 2024

Clin Exp Med

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Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort). We assessed the drug retention rates of b/targeted synthetic DMARDs with different modes of action (tumour necrosis factor inhibitors (TNFis), immunoglobulins fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), interleukin-6 receptor inhibitors (IL-6Ris), and JAKis) in patients with RA stratified by pre-treatment estimated glomerular filtration rate (eGFR) levels. The time to discontinuation of bDMARDs or JAKis was analysed using a multivariate Cox proportional hazards model This study included 3775 patients, who were classified into three groups (the normal group (eGFR ≥ 60 mL/min/1.73 m2): 2893 patients; CKDa group (eGFR 45–60 mL/min/1.73 m2): 551; and CKDb group (eGFR < 45 mL/min/1.73 m2): 331). In the CKDb group, the 12-month drug retention rate due to adverse events (AE) was the lowest in patients treated with JAKi (TNFi: 93.1%; IL-6Ri: 94.1%; CTLA-4-Ig: 92.3%; JAKi: 75.1%). In the normal and CKDa groups, drug retention rates due to AE were similar among patients treated with bDMARDs and JAKi. In contrast, drug retention rates due to inefficacy were similar between bDMARDs and JAKis in all groups. In the Cox-proportional model, in the CKDb group, TNFi, IL-6Ri, and CTLA-4-Ig showed lower incidence of drug discontinuation due to AE than JAKis (TNFi: hazard ratio = 0.23 (95% confidence interval 0.09–0.61), IL-6Ri: 0.34 (0.14–0.81), CTLA-4-Ig: 0.36 (0.15–0.89)). JAKis showed the lowest drug retention due to AE in patients with moderate-to-severe and severe renal impairment (eGFR < 45 mL/min/1.73 m2). Physicians should pay more attention to renal function when using JAKis than when using bDMARDs.

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“…However, the majority of these studies have been carried out in rheumatoid or psoriatic arthritis patients. Although certain studies found no specific pattern regarding time to VTE onset with tofacitinib or upadacitinib use [ [1] , [2] , [3] , [4] , [5] , [6] ], other larger studies of tofacitinib or upadacitinib reported a time to VTE event primarily within a shorter timeframe of <120 days in addition to an overall distribution with positive skew [ [7] , [8] , [9] , [10] ]. If VTE events were to primarily cluster within the 2 to 12-week period of efficacy assessment, then initiating a JAKi for remission induction or to trial efficacy in patients that require additional disease control could lead to an avoidable consequence of VTE before demonstrating benefit.…”

mentioning

confidence: 99%

Earlier onset of acute venous thromboembolism with upadacitinib compared with tofacitinib during Janus kinase inhibitor therapy

Lowell,

Sharma,

Sultan

2024

Research and Practice in Thrombosis and Haemostasis

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Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system

Cited by 7 publications

References 41 publications

Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018–2023

Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018–2023

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study

Earlier onset of acute venous thromboembolism with upadacitinib compared with tofacitinib during Janus kinase inhibitor therapy

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