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

ABSTRACT

Background

Upadacitinib was approved to treat rheumatoid arthritis, psoriasis, ulcerative colitis, ankylosing spondylitis, and atopic dermatitis. This study assessed the adverse events (AEs) associated with upadacitinib by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods

Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of upadacitinib-associated AEs.

Results

A total of 3,837,420 reports of AEs were collected from the FAERS database, of which 4494 reports were identified with upadacitinib as the “primary suspect (PS)”. Upadacitinib-induced AEs occurrence targeted 27 system organ clases (SOCs). A total of 200 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected significant AEs, such as arthralgia, musculoskeletal stiffness, diverticulitis, and cataract might also occur. The median onset time of upadacitinib-associated AEs was 65 days (interquartile range [IQR] 21–182 days), and most of the onsets occurred within the first 1, 2, 3, and 4 months after initiation of upadacitinib.

Conclusion

This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of upadacitinib.

KEYWORDS:

• upadacitinib
• pharmacovigilance
• adverse events
• post-marketing surveillance
• FAERS
• data mining

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. This reviewer is the founder and part owner of Causa Research and holds stock in Sensal Health. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contributions

Xiang-Ping Wu drafted the manuscript. All authors participated in data analysis and interpretation, manuscript revision, and final approval of the submission.

Ethical approval

The FAERS database contains anonymized patient information. The Hospital Ethics Committee has confirmed that no ethical approval was required.

Data availability statement

The data that support the findings of this study are openly available in FAERS database at https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.

Scientific accuracy review

Abbvie provided a scientific accuracy review at the request of the journal editor.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2223952

Additional information

Funding

This paper was funded by Hunan Provincial Natural Science Foundation of 2021 (2021JJ31043).