Treatment-emergent adverse events throughout the study
| Event (E/100 PY (95% CI)) | Any UPA 15 mg QD N=182 (308.6 PY) |
| AE | 749 (242.7 (225.6–260.7)) |
| Serious AE | 19 (6.2 (3.7–9.6)) |
| AE leading to discontinuation | 17 (5.5 (3.2–8.8)) |
| Infection | 246 (79.7 (70.1–90.3)) |
| Serious infection | 0 |
| Opportunistic infection excluding TB and herpes zoster* | 2 (0.6 (0.1–2.3)) |
| Active TB | 0 |
| Herpes zoster† | 5 (1.6 (0.5–3.8)) |
| Creatine phosphokinase elevation‡ | 35 (11.3 (7.9–15.8)) |
| Hepatic disorder§ | 32 (10.4 (7.1–14.6)) |
| Neutropenia¶ | 9 (2.9 (1.3–5.5)) |
| Anaemia¶ | 5 (1.6 (0.5–3.8)) |
| Lymphopenia¶ | 3 (1.0 (0.2–2.8)) |
| Malignancy** | 1 (0.3 (0.0–1.8)) |
| Adjudicated venous thromboembolic event†† | 1 (0.3 (0.0–1.8)) |
| Inflammatory bowel disease‡‡ | 1 (0.3 (0.0–1.8)) |
| Uveitis§§ | 16 (5.2 (3.0–8.4)) |
| Death | 0 |
*Two non-serious events of oesophageal candidiasis in the same patient; each event was moderate, non-serious and assessed by the investigator as having a reasonable possibility of being related to study drug. Study drug was temporarily interrupted for each event.
†Five events in four patients (three from Japan); all non-serious, mild or moderate and limited to one dermatome.
‡All but one event were non-serious, and none led to study drug discontinuation; the majority were asymptomatic, and the three symptomatic patients had muscle pain due to alternative explanations, such as increased physical activity.
§Majority based on asymptomatic alanine aminotransferase/aspartate aminotransferase elevations; all were non-serious, and none led to study drug discontinuation.
¶All events were non-serious, and none led to study drug discontinuation.
**Squamous cell carcinoma of the tongue (stage IV) in 60-year-old male former smoker (approximately one pack a day for 40 years); the investigator assessed the event as having no reasonable possibility of being study drug related, and the patient discontinued the study drug. The malignancy occurred on day 146 of upadacitinib therapy.
††Pulmonary embolism in one female patient with history of thrombosis of the lower leg prior to study entry, impaired glucose tolerance, cigarette smoking, sedentary lifestyle, and obesity; assessed as not related to study drug by the investigator. The venous thromboembolic event occurred on day 568 of upadacitinib therapy.
‡‡Event of colitis with appendix swelling in 23-year-old male patient with no prior history of inflammatory bowel disease.
§§Sixteen uveitis AEs in 10 patients; 9 patients were HLA-B27 positive, 9 patients had a history of uveitis, and 15 of 16 events were mild or moderate. Most events were transient, resolved with local treatment (corticosteroid eye drop), and did not lead to interruption or discontinuation of study drug (except one patient with mild uveitis who discontinued the study); all were non-serious.
AE, adverse event; PY, patient years; QD, once daily; TB, tuberculosis; UPA, upadacitinib.