Table 2.
Overview of safety measures including exposure, treatment-emergent AEs, and AEs of special interest
| Placebo-controlled (to week 16) | All-bari-2-mg-AD | ||
|---|---|---|---|
| Placebo (N = 889) | Baricitinib 2 mg (N = 721) | All-bari-2-mg-AD (N = 1598) | |
| Exposure | |||
| Total patient-years | 252.7 | 210.6 | 1434.2 |
| No. of patients with ≥ 52 weeksa, n (%) | – | – | 729 (45.6) |
| No. of patients with ≥ 104 weeks, n (%) | – | – | 34 (2.1) |
| Median duration, days | 113 | 113 | 330 |
| Maximum exposure, days | 168 | 128 | 869 |
| AEs, n (%) [IR]b | |||
| Any treatment-emergent AE | 460 (51.6) [277.6] | 421 (57.9) [325.5] | 1032 [159.6] |
| Serious AE | 24 (2.7) [9.2] | 12 (1.6) [5.2] | 68 [4.7] |
| Interruption of the study drug because of AE | 18 (2.0) [7.0] | 28 (3.5) [12.0] | 118 [8.4] |
| Discontinuation of the study drug because of AE | 17 (1.8) [6.1] | 14 (1.9) [6.2] | 56 [3.8] |
| Death | 0 | 0 | 0 |
| Infections, n (%) [IR]b | |||
| Treatment-emergent infections | 252 (28.4) [117.0] | 251 (34.4) [146.0] | 732 [80.6] |
| Serious infections | 6 (0.7) [2.5] | 4 (0.5) [1.4] | 22 [1.5] |
| Skin infections requiring antibiotic treatment | 46 (5.4) [19.0] | 37 (5.5) [19.1] | 37 [2.6] |
| Herpes simplex cluster | 23 (2.8) [9.8] | 27 (3.8) [13.2] | 108 [7.7] |
| Herpes simplex | 8 (0.9) [3.2] | 13 (2.0) [7.1] | 38 [2.6] |
| Oral herpes | 10 (1.3) [4.5] | 12 (1.5) [5.0] | 58 [4.0] |
| Kaposi’s varicelliform eruption | 0 | 1 (0.2) [0.7] | 5 [0.3] |
| Genital herpes simplex | 0 | 1 (0.1) [0.3] | 2 [0.1] |
| Genital herpes | 1 (0.2) [0.7] | 0 | 2 [0.1] |
| Ophthalmic herpes simplex | 0 | 0 | 3 [0.2] |
| Herpes opthalmic | 0 | 0 | 2 [0.1] |
| Eczema herpeticum | 4 (0.4) [1.3] | 0 | 15 [1.0] |
| Eczema herpeticum cluster | 4 (0.4) [1.3] | 1 (0.2) [0.7] | 20 [1.4] |
| Eczema herpeticum | 4 (0.4) [1.3] | 0 | 15 [1.0] |
| Kaposi’s varicelliform eruption | 0 | 1 (0.2) [0.7] | 5 [0.3] |
| Herpes zoster | 3 (0.3) [1.0] | 6 (0.8) [2.7] | 30 [2.1] |
| Tuberculosis | 0 | 0 | 0 |
| Opportunistic infection excluding tuberculosisc | 1 (0.1) [0.4] | 1 (0.1) [0.3] | 3 [0.2] |
| Malignancy, n (%) [IR]b | |||
| Malignancies other than NMSC | 2 (0.2) [0.66] | 0 | 5 [0.34] |
| NMSC | 1 (0.2) [0.68] | 0 | 4 [0.27] |
| Cardiovascular AEs of special interest, n (%) [IR]b | |||
| MACEd,e | 0 | 0 | 2/1561 [0.14] |
| DVTd | 0 | 0 | 0 |
| PEd | 0 | 0 | 0 |
| Peripheral venous thrombosisd | 0 | 0 | 1/1561 [0.07] |
| Arterial thromboembolic eventc | 0 | 0 | 1 [0.07] |
| Gastrointestinal disorder, n (%) [IR]b | |||
| Gastrointestinal perforation | 0 | 0 | 0 |
| Ocular AEs, n (%) [IR]b | |||
| Conjunctival disorders | 18 (2.4) [8.7] | 15 (2.0) [6.8] | 51 [3.5] |
AD atopic dermatitis, AE adverse event, DVT deep vein thrombosis, IR incidence rate, MACE major adverse cardiovascular event, N number of patients in the analysis set, n number of patients in the specified category, NMSC non-melanoma skin cancer, PE pulmonary embolism
aAccording to the week 52 minimum protocol window of 4 days = 360 days
bFor the placebo-controlled dataset, study-size adjusted percentages and IRs are shown
cMedically reviewed by a blinded internal committee
dAll AEs suggestive of a possible MACE, DVT, PE, or other peripheral venous thrombosis were adjudicated in a blinded manner by an experienced external independent clinical event committee. Adjudication determined whether these AEs qualified as MACE, DVT, PE, or other peripheral venous thrombosis based on evaluations of case descriptions and any diagnostic tests available. AEs meeting the adjudication committee definitions for these specific events were considered positively adjudicated. A positively adjudicated event provides additional diagnostic confirmation but does not assess a causal relationship to the study drug
eA MACE was defined as cardiovascular death, myocardial infarction, or stroke as adjudicated by an external independent clinical event committee