Table 4.
Incidence and exposure-adjusted incidence rates of AESIs in the upadacitinib Japanese and global RA populations
| AESIsa | Japanese RA population | Global RA population | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Upadacitinib 7.5 mg once daily [n = 121] |
Upadacitinib 15 mg once daily [n = 126] |
Upadacitinib 30 mg once daily [n = 124] |
Upadacitinib 6 mg twice daily/ 15 mg once daily [n = 2883] |
Upadacitinib 12 mg twice daily/ 30 mg once daily [n = 1375] |
||||||
| n (%) | n/100 PY (95% CI) | n (%) | n/100 PY (95% CI) | n (%) | n/100 PY (95% CI) | n (%) | n/100 PY (95% CI) | n (%) | n/100 PY (95% CI) | |
| Infection | 93 (76.9) | 117.0 (94.4–143.3) | 103 (81.7) | 116.8 (95.3–141.6) | 106 (85.5) | 156.1 (127.8–188.7) | 1470 (51.0) | 68.2 (64.8–71.8) | 846 (61.5) | 91.5 (85.5–97.9) |
| Serious infection | 10 (8.3) | 4.9 (2.4–9.0) | 10 (7.9) | 4.8 (2.3–8.9) | 19 (15.3) | 10.6 (6.4–16.5) | 98 (3.4) | 2.9 (2.4–3.5) | 90 (6.5) | 5.5 (4.4–6.7) |
| Opportunistic infection | 2 (1.7) | 1.0 (0.1–3.5) | 5 (4.0) | 2.4 (0.8–5.5) | 15 (12.1) | 8.5 (4.7–13.9) | 26 (0.9) | 0.8 (0.5–1.1) | 28 (2.0) | 1.7 (1.1–2.4) |
| Herpes zoster | 15 (12.4) | 7.8 (4.3–12.8) | 24 (19.0) | 12.4 (7.9–18.4) | 28 (22.6) | 16.7 (11.1–24.2) | 124 (4.3) | 3.7 (3.1–4.4) | 113 (8.2) | 7.0 (5.8–8.4) |
| Active/latent tuberculosis | 0 | 0 | 1 (0.8) | 0.5 (0.0–2.6) | 2 (1.6) | 1.1 (0.1–3.9) | 67 (2.3) | 2.0 (1.5–2.5) | 25 (1.8) | 1.5 (1.0–2.2) |
| NMSC | 0 | 0 | 0 | 0 | 0 | 0 | 10 (0.3) | 0.3 (0.1–0.5) | 12 (0.9) | 0.7 (0.4–1.3) |
| Malignancy other than NMSC | 1 (0.8) | 0.5 (0.0–2.7) | 2 (1.6) | 0.9 (0.1–3.4) | 3 (2.4) | 1.6 (0.3–4.7) | 28 (1.0) | 0.8 (0.5–1.2) | 19 (1.4) | 1.1 (0.7–1.8) |
| Lymphoma | 0 | 0 | 0 | 0 | 1 (0.8) | 0.5 (0.0–3.0) | 1 (< 0.1) | < 0.1 (0.0–0.2) | 2 (0.1) | 0.1 (0.0–0.4) |
| Hepatic disorders | 13 (10.7) | 6.8 (3.6–11.6) | 16 (12.7) | 8.2 (4.7–13.3) | 11 (8.9) | 6.3 (3.1–11.2) | 249 (8.6) | 7.7 (6.8–8.7) | 116 (8.4) | 7.3 (6.0–8.7) |
| Gastrointestinal perforation | 0 | 0 | 1 (0.8) | 0.5 (0.0–2.6) | 1 (0.8) | 0.5 (0.0–3.0) | 6 (0.2) | 0.2 (0.1–0.4) | 6 (0.4) | 0.4 (0.1–0.8) |
| Anemia | 4 (3.3) | 2.0 (0.5–5.1) | 4 (3.2) | 1.9 (0.5–4.9) | 18 (14.5) | 10.3 (6.1–16.3) | 123 (4.3) | 3.7 (3.1–4.4) | 77 (5.6) | 4.7 (3.7–5.9) |
| Neutropenia | 5 (4.1) | 2.5 (0.8–5.9) | 3 (2.4) | 1.4 (0.3–4.2) | 13 (10.5) | 7.7 (4.1–13.1) | 84 (2.9) | 2.5 (2.0–3.1) | 81 (5.9) | 5.1 (4.0–6.3) |
| Lymphopenia | 7 (5.8) | 3.5 (1.4–7.2) | 9 (7.1) | 4.4 (2.0–8.3) | 9 (7.3) | 5.0 (2.3–9.5) | 59 (2.0) | 1.7 (1.3–2.3) | 45 (3.3) | 2.7 (2.0–3.7) |
| CPK elevation | 9 (7.4) | 4.6 (2.1–8.7) | 17 (13.5) | 8.8 (5.1–14.0) | 24 (19.4) | 14.7 (9.4–21.8) | 160 (5.5) | 4.9 (4.1–5.7) | 144 (10.5) | 9.3 (7.8–11.0) |
| Renal dysfunction | 1 (0.8) | 0.5 (0.0–2.7) | 1 (0.8) | 0.5 (0.0–2.6) | 4 (3.2) | 2.2 (0.6–5.5) | 13 (0.5) | 0.4 (0.2–0.7) | 16 (1.2) | 1.0 (0.5–1.5) |
| Adjudicated MACEb | 1 (0.8) | 0.5 (0.0–2.7) | 0 | 0 | 2 (1.6) | 1.1 (0.1–3.9) | 16 (0.6) | 0.5 (0.3–0.8) | 15 (1.1) | 0.9 (0.5–1.5) |
| Adjudicated VTEc | 0 | 0 | 1 (0.8) | 0.5 (0.0–2.6) | 1 (0.8) | 0.5 (0.0–3.0) | 17 (0.6) | 0.5 (0.3–0.8) | 6 (0.4) | 0.4 (0.1–0.8) |
| Pulmonary embolism | 0 | 0 | 0 | 0 | 0 | 0 | 12 (0.4) | 0.4 (0.2–0.6) | 3 (0.2) | 0.2 (0.0–0.5) |
| Deep vein thrombosis | 0 | 0 | 1 (0.8) | 0.5 (0.0–2.6) | 1 (0.8) | 0.5 (0.0–3.0) | 9 (0.3) | 0.3 (0.1–0.5) | 5 (0.4) | 0.3 (0.1–0.7) |
AESI adverse event of special interest, CI confidence interval, CPK creatine phosphokinase, MACE major adverse cardiovascular events, MedDRA Medical Dictionary for Regulatory Activities, NMSC non-melanoma skin cancer, PY patient-years, RA rheumatoid arthritis, VTE venous thromboembolism
aAESIs were identified by a Standardized MedDRA query or Company MedDRA query with an onset date on or after the first dose of upadacitinib and no more than 30 days after the last dose of upadacitinib
bDefined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
cIncluding pulmonary embolism or deep vein thrombosis