Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease
Bibliographic record
Abstract
INTRODUCTION: We report the long-term safety of upadacitinib (oral, selective, and reversible Janus kinase inhibitor) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), atopic dermatitis (AD), Crohn's disease (CD), and ulcerative colitis (UC). METHODS: Data were analyzed from 16 studies (data cutoff August 15, 2024). Each treatment group was pooled across studies within each indication. Active comparator arms included adalimumab (RA/PsA) and methotrexate (RA). Treatment-emergent adverse events (TEAEs) were reported as exposure-adjusted incidence rates per 100 patient-years (n/100 PY). RESULTS: This analysis included 8632 (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286; AD, n = 2683; CD, n = 450; UC, n = 501) upadacitinib-treated patients over 27,164.2 patient-years (range 199.4-12,315.8 PY across indications). Rates (n/100 PY) of any TEAEs ranged from 112.0 (AS) to 401.1 (RA). Most frequently reported TEAEs included COVID-19, upper respiratory tract infection, nasopharyngitis, herpes zoster, urinary tract infection, and acne (primarily patients with AD). Serious TEAEs ranged from 4.5 (AD) to 11.0 (UC), and those leading to discontinuation ranged from 2.9 (AS) to 8.3 (UC). TEAEs leading to death ranged from 0 (nr-axSpA, UC) to 0.7 (RA). Among upadacitinib-treated patients across indications, rates of adverse events of special interest ranged from 1.3 to 4.6 (serious infection), 2.4-6.6 (herpes zoster), 0.2-0.9 (malignancy excluding nonmelanoma skin cancer [NMSC]), 0-1.4 (NMSC), 0-0.5 (major adverse cardiovascular event [MACE]), 0-0.9 (venous thromboembolism [VTE]), and 0-9.2 (elevated creatine kinase). In RA and PsA, herpes zoster, NMSC, and elevated creatine kinase rates were numerically higher with upadacitinib vs active comparators. Serious infection, herpes zoster, malignancy (excluding NMSC), NMSC, MACE, and VTE rates remained stable over time. CONCLUSION: This descriptive analysis indicates a long-term safety profile of upadacitinib consistent with previous reports, further supporting long-term treatment of chronic diseases with upadacitinib. Variations in TEAE rates across indications likely reflected differences in populations and underlying comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT04169373, NCT03569293, NCT03568318, NCT03607422, NCT03345823, NCT02819635.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".