Table 3.
Summary of treatment-emergent adverse events (all causalities) in the all-exposure pool
| Ritlecitinib 50 mg ± 200-mg loading dosea (n = 1228) | Any ritlecitinib (n = 1294) | |||
|---|---|---|---|---|
| n (%) | IR (95% CI)b | n (%) | IR (95% CI)b | |
| No. of patients evaluable for AEs | 1228 | 1294 | ||
| No. of AEs | 4368 | 5234 | ||
| Patients with AEs | 989 (80.5) | 160.55 (150.77, 170.80) | 1094 (84.5) | 179.76 (169.33, 190.65) |
| Patients with SAEs | 52 (4.2) | 2.79 (2.10, 3.65) | 57 (4.4) | 2.64 (2.01, 3.40) |
| Patients with severe AEs | 66 (5.4) | 3.59 (2.79, 4.55) | 83 (6.4) | 3.91 (3.13, 4.83) |
| Deaths | 2 (0.2)c | 0.10 (0.01, 0.36) | 2 (0.2)c | 0.09 (0.01, 0.31) |
| Patients discontinued from study or study drug due to AEsd | 68 (5.5) | 3.63 (2.83, 4.58) | 78 (6.0) | 3.59 (2.84, 4.45) |
| Patients with temporary discontinuation due to AEs | 259 (21.1) | 15.78 (13.93, 17.81) | 284 (21.9) | 15.10 (13.42, 16.95) |
| AEs occurring in ≥ 5% of patients in any treatment group by PT | ||||
| Headache | 186 (15.1) | 10.72 (9.25, 12.36) | 229 (17.7) | 11.90 (10.43, 13.53) |
| SARS-CoV-2 positive test | 192 (15.6) | 10.68 (9.23, 12.29) | 201 (15.5) | 9.75 (8.47, 11.18) |
| Nasopharyngitis | 117 (9.5) | 6.57 (5.45, 7.86) | 160 (12.4) | 8.17 (6.97, 9.51) |
| Acne | 111 (9.0) | 6.17 (5.09, 7.42) | 135 (10.4) | 6.75 (5.68, 7.97) |
| Upper respiratory tract infection | 104 (8.5) | 5.91 (4.84, 7.14) | 132 (10.2) | 6.48 (5.44, 7.66) |
| Pyrexia | 93 (7.6) | 5.01 (4.06, 6.13) | 98 (7.6) | 4.64 (3.79, 5.64) |
| Cough | 93 (7.6) | 5.15 (4.17, 6.29) | 96 (7.4) | 4.54 (3.70, 5.53) |
| Fatigue | 77 (6.3) | 4.15 (3.29, 5.17) | 91 (7.0) | 4.33 (3.51, 5.30) |
| Urticaria | 74 (6.0) | 4.02 (3.17, 5.03) | 88 (6.8) | 4.25 (3.43, 5.22) |
| AEs of special intereste | ||||
| Serious infections | 12 (1.0) | 0.66 (0.35, 1.13) | 14 (1.1) | 0.64 (0.36, 1.06) |
| Opportunistic infections | 1 (< 0.1) | 0.05 (0.00, 0.25) | 1 (< 0.1) | 0.05 (0.00, 0.23) |
| Herpes zoster | 18 (1.5) | 0.99 (0.60, 1.55) | 20 (1.5) | 0.92 (0.57, 1.40) |
| Herpes simplex | 25 (2.0) | 1.31 (0.86, 1.91) | 37 (2.9) | 1.72 (1.22, 2.35) |
| Malignancies (excluding NMSC) | 7 (0.6) | 0.37 (0.16, 0.75) | 7 (0.5) | 0.32 (0.14, 0.64) |
| NMSC | 3 (0.2) | 0.15 (0.03, 0.43) | 3 (0.2) | 0.14 (0.03, 0.38) |
| Breast cancerf | 4 (0.5) | 0.39 (0.12, 0.97) | 4 (0.5) | 0.35 (0.10, 0.85) |
| MACEg | 3 (0.2) | 0.15 (0.03, 0.43) | 3 (0.2) | 0.14 (0.03, 0.38) |
| Thromboembolic events (PE) | 1 (< 0.1) | 0.06 (0.00, 0.29) | 1 (< 0.1) | 0.05 (0.00, 0.23) |
| Peripheral neuropathy | 3 (0.2) | 0.16 (0.03, 0.45) | 4 (0.3) | 0.18 (0.05, 0.45) |
| Paresthesia and dysesthesia | 21 (1.7) | 1.11 (0.69, 1.67) | 26 (2.0) | 1.20 (0.80, 1.75) |
| Sensorineural hearing lossh | 12 (1.0) | 0.67 (0.36, 1.16) | 14 (1.1) | 0.64 (0.36, 1.06) |
AE adverse event, IR incidence rate, MACE major adverse cardiovascular event, NMSC nonmelanoma skin cancer, PE pulmonary embolism, PT preferred term, PY patient-years, SAE serious adverse event
aPatients received ritlecitinib 50 mg once daily (QD) with or without an initial 4-week 200-mg QD loading dose
bStudy size–adjusted IRs per 100 PY and mid-p gamma CIs
cTwo deaths were reported in the all-exposure pool: breast cancer (spindle cell carcinoma) and acute respiratory failure/cardiorespiratory arrest. Both events were determined by the investigator to be unrelated to the study treatment
dPatients with an AE record that indicated that the AE caused the patient to be discontinued from the study or study drug
eOpportunistic infections, malignancies, MACE, non-MACE, thromboembolic events, peripheral neuropathy, paresthesia and dysesthesia, and sensorineural hearing loss were adjudicated by independent clinical event committees
fDenominator and patient-years were adjusted to reflect the female patient population
gMACE was defined as a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. There was one event of percutaneous transluminal coronary angioplasty/percutaneous coronary intervention in the 50-mg group that was considered non-MACE
hSensorineural hearing loss included Medical Dictionary of Regulatory Activities (MedDRA) PTs of deafness neurosensory, deafness unilateral, and hypoacusis. PT terms defined by MedDRA do not necessarily indicate that patients developed deafness