Why carry out this study?
|
A pooled analysis of safety data for baricitinib in participants with moderate-to-severe atopic dermatitis from eight clinical studies confirmed the established safety profile of baricitinib. |
In this pooled analysis, the safety data for baricitinib in the Japanese subpopulation, which represented one of the major subpopulations in the pooled analysis, are reported from five placebo-controlled clinical studies and one long-term extension study with exposure up to 2 years. |
What was learned from the study?
|
In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. |
In the dataset that included all baricitinib doses, no gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with baricitinib exposure up to 2 years, and there were no deaths. |
These findings in the subpopulation of Japanese participants are consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe atopic dermatitis. |
Introduction
Methods
Study Design and Participants
Analysis Datasets
Safety Outcomes
Statistical Analysis
Results
Study Participants in the Japanese Subpopulation
Placebo controlled (to week 16) | All-bari-ADa, N = 341 | |||
---|---|---|---|---|
Placebo, N = 134 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | ||
Age, years | 35.9 (10.9) | 35.6 (11.1) | 34.2 (11.3) | 35.7 (11.0) |
Female, n (%) | 36 (26.9) | 22 (21.8) | 19 (21.3) | 87 (25.5) |
Body mass index, kg/m2 | 24.0 (4.5) | 23.8 (4.1) | 23.6 (3.9) | 23.8 (4.1) |
Duration since AD diagnosis, years | 25.3 (13.5) | 23.2 (12.7) | 23.1 (12.9) | 24.9 (12.7) |
Geographic region Japan, n (%) | 134 (100) | 101 (100) | 89 (100) | 341 (100) |
Prior topical therapy | ||||
Corticosteroids, n (%) | 132 (98.5) | 101 (100) | 89 (100) | 337 (98.8) |
Calcineurin inhibitor, n (%) | 80 (64.5) | 60 (70.6) | 58 (73.4) | 211 (68.7) |
Prior systemic therapy | ||||
Cyclosporine, n (%) | 17 (14.9) | 17 (25.0) | 11 (15.7) | 49 (17.8) |
Disease characteristics | ||||
vIGA-AD score of 4 (severe disease), n (%) | 55 (43.7) | 40 (42.1) | 35 (42.2) | 143 (43.5) |
EASI score | 35.2 (14.2) | 33.9 (13.4) | 34.7 (12.5) | 34.9 (13.5) |
SCORAD | 69.8 (14.5) | 67.9 (14.4) | 69.1 (13.1) | 69.2 (14.2) |
Percent body surface area affected | 63.2 (21.6) | 60.5 (20.9) | 62.1 (21.5) | 62.2 (21.4) |
DLQI | 11.2 (6.3) | 11.8 (6.7) | 10.6 (6.2) | 11.4 (6.6) |
Itch NRS | 6.7 (2.0) | 6.7 (2.1) | 6.3 (2.2) | 6.5 (2.1) |
Treatment-Emergent Adverse Events in the Japanese Subpopulation
Placebo controlled (to week 16) | 2-mg—4-mg extended | All-bari-ADa, N = 341 | ||||
---|---|---|---|---|---|---|
Placebo, N = 134 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | ||
Exposure | ||||||
Total participant-years | 39.1 | 30.7 | 26.9 | 78.6 | 93.2 | 371.7 |
Participants with ≥ 52 weeks, n (%) | – | – | – | 32 (31.7) | 43 (48.3) | 201 (58.9) |
Median duration, days | 113.0 | 113.0 | 113.0 | 315.0 | 362.0 | 371.0 |
Longest exposure, days | 121 | 120 | 119 | 675 | 702 | 703 |
Adverse events, n (adj %) [adj IR]b | ||||||
Any TEAE | 63 (44.9) [229.1] | 51 (54.4) [261.0] | 52 (57.3) [310.3] | 60 [197.7] | 69 [200.7] | 245 [149.3] |
SAE | 3 (1.9) [6.7] | 0 | 3 (2.9) [9.3] | 2 [1.6] | 6 [6.0] | 13 [3.5] |
Interruption of study drug due to AE | 0 | 1 (1.4) [4.7] | 2 (2.5) [8.6] | 3 [3.3] | 5 [6.4] | 17 [4.6] |
Discontinuation of study drug due to AE | 0 | 2 (2.2) [6.9] | 5 (4.5) [13.8] | 2 [2.6] | 7 [7.0] | 16 [4.2] |
Death, n (IR) | 0 | 0 | 0 | 0 | 0 | 0 |
Infections, n (adj %) [adj IR]b | ||||||
Treatment-emergent infections | 34 (25.2) [100.0] | 35 (36.3) [146.9] | 35 (40.0) [165.0] | 45 [108.6] | 51 [105.7] | 187 [84.9] |
Serious infection | 0 | 0 | 1 (1.3) [4.0] | 2 [1.6] | 2 [1.8] | 5 [1.3] |
Herpes zoster | 0 | 1 (1.4) [4.7] | 0 | 1 [1.4] | 2 [2.6] | 9 [2.4] |
Herpes simplexc | 3 (1.9) [6.5] | 5 (5.4) [18.3] | 7 (8.0) [27.0] | 9 [10.9] | 9 [10.1] | 29 [8.1] |
Eczema herpeticumd | 0 | 1 (1.4) [4.7] | 4 (5.2) [17.9] | 2 [2.5] | 4 [4.7] | 8 [2.1] |
Skin infections needing antibiotic treatment | 8 (7.1) [24.6] | 6 (5.1) [17.3] | 3 (3.5) [11.2] | 6 [7.1] | 3 [3.0] | 13 [3.6] |
TB | 0 | 0 | 0 | 0 | 0 | 0 |
Opportunistic infection excl TB | 0 | 0 | 0 | 0 | 1 [1.7] | 1 [0.3] |
Malignancy, n (adj %) [adj IR]b | ||||||
Malignancy excluding NMSC | 0 | 0 | 0 | 0 | 0 | 2 [0.52] |
NMSC | 0 | 0 | 0 | 0 | 0 | 0 |
Adverse CV events, n (adj %) [adj IR]b | ||||||
MACE | 0 | 0 | 0 | 0 | 0 | 0 |
VTE (DVT and/or PE) | 0 | 0 | 0 | 0 | 0 | 0 |
PE | 0 | 0 | 0 | 0 | 0 | 0 |
GI disorders, n (adj %) [adj IR]b | ||||||
GI perforations | 0 | 0 | 0 | 0 | 0 | 0 |
Ocular adverse events, n (adj %) [adj IR]b | ||||||
Conjunctival disorders | 4 (2.8) [9.7] | 0 | 1 (1.3) [4.2] | 0 | 1 [0.9] | 7 [1.9] |
Placebo controlled (to week 16) | 2-mg—4-mg extended | All-bari-ADa, N = 341 | ||||
---|---|---|---|---|---|---|
Placebo, N = 134 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | ||
TEAE occurring in ≥ 2% of participants in any group in the placebo-controlled datasets, n (adj %) [adj IR] | ||||||
Nasopharyngitis | 18 (13.3) [48.1] | 16 (16.9) [60.8] | 21 (24.0) [90.5] | 23 [44.3] | 32 [51.7] | 97 [32.8] |
Kaposi’s varicelliform eruption | 0 | 1 (1.4) [4.7] | 4 (5.2) [17.9] | 2 [2.5] | 4 [4.7] | 8 [2.1] |
Acne | 3 (1.9) [6.6] | 1 (1.4) [4.7] | 4 (4.6) [15.4] | 5 [6.9] | 8 [9.8] | 26 [7.2] |
Herpes simplex | 2 (1.3) [4.3] | 2 (2.7) [8.9] | 3 (3.3) [10.9] | 4 [5.5] | 6 [5.9] | 17 [4.6] |
Headache | 2 (1.3) [4.3] | 5 (6.3) [21.2] | 3 (2.9) [9.2] | 6 [9.6] | 3 [3.1] | 14 [3.8] |
Folliculitis | 3 (2.7) [9.1] | 5 (4.8) [16.8] | 3 (2.8) [9.4] | 9 [11.5] | 4 [4.1] | 29 [8.1] |
Abdominal pain upper | 1 (0.6) [2.2] | 0 | 2 (2.6) [8.3] | 0 | 2 [1.9] | 2 [0.5] |
Tonsillitis | 2 (1.3) [4.4] | 1 (0.6) [2.2] | 2 (2.5) [8.5] | 2 [1.7] | 2 [2.7] | 4 [1.1] |
Blood creatine increased | 0 | 0 | 2 (2.5) [8.0] | 0 | 2 [1.8] | 2 [0.5] |
Hyperuricemia | 0 | 0 | 2 (2.1) [6.6] | 0 | 2 [2.0] | 2 [0.5] |
Upper respiratory tract infection | 2 (1.4) [4.8] | 0 | 2 (2.0) [6.4] | 0 | 3 [2.9] | 8 [2.1] |
Skin papilloma | 0 | 2 (2.0) [6.9] | 1 (1.3) [4.6] | 4 [5.7] | 4 [4.6] | 13 [3.5] |
Eczema | 0 | 2 (2.7) [8.9] | 1 (1.3) [4.0] | 3 [5.2] | 2 [1.8] | 5 [1.3] |
Otitis externa | 0 | 4 (3.5) [11.4] | 1 (1.3) [4.1] | 5 [6.2] | 1 [0.9] | 12 [3.2] |
Dyshidrotic eczema | 0 | 3 (3.5) [11.6] | 1 (0.7) [2.4] | 4 [6.4] | 3 [2.9] | 10 [2.7] |
Permanent discontinuation of study drug due to adverse event by system organ class, n (adj %) [adj IR] | ||||||
Skin and subcutaneous tissue disordersb | 0 | 1 (0.9) [2.3] | 3 (2.4) [7.3] | 1 [0.9] | 3 [3.1] | 5 [1.3] |
Infections and infestations | 0 | 1 (1.4) [4.6] | 1 (1.3) [4.0] | 1 [1.7] | 1 [0.9] | 3 [0.8] |
Investigations | 0 | 0 | 1 (0.9) [2.5] | 0 | 3 [3.0] | 4 [1.1] |
Cardiac disorders | 0 | 0 | 0 | 0 | 0 | 1 [0.3] |
Eye disorders | 0 | 0 | 0 | 0 | 0 | 1 [0.3] |
Neoplasms benign, malignant, and unspecifiedc | 0 | 0 | 0 | 0 | 0 | 1 [0.3] |
Psychiatric disorders | 0 | 0 | 0 | 0 | 0 | 1 [0.3] |
Laboratory Values and Clinical Chemistry in the Japanese Subpopulation
Treatment-emergent changes, n/NAR (%) | Placebo-controlled (to week 16) | 2-mg – 4-mg extended | All-bari-ADa, N = 341 | |||
---|---|---|---|---|---|---|
Placebo, N = 134 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | Baricitinib 2 mg, N = 101 | Baricitinib 4 mg, N = 89 | ||
LDL-C ≥ 130 mg/dL | 5/105 (4.8) | 12/90 (13.3) | 14/73 (19.2) | 16/90 (17.8) | 22/73 (30.1) | 69/278 (24.8) |
HDL-C ≥ 60 mg/dL | 16/71 (22.5) | 15/62 (24.2) | 17/49 (34.7) | 21/62 (33.9) | 20/49 (40.8) | 67/186 (36.0) |
Triglycerides ≥ 500 mg/dL | 3/125 (2.4) | 1/100 (1.0) | 2/88 (2.3) | 1/100 (1.0) | 3/88 (3.4) | 7/335 (2.1) |
Creatine phosphokinase (U/L) | ||||||
> ULN | 8/124 (6.5) | 14/95 (14.7) | 18/85 (21.2) | 18/95 (18.9) | 27/85 (31.8) | 78/314 (24.8) |
> 2.5 × ULN | 2/132 (1.5) | 2/99 (2.0) | 2/87 (2.3) | 3/99 (3.0) | 6/87 (6.9) | 20/334 (6.0) |
> 5 × ULN | 2/133 (1.5) | 1/101 (1.0) | 2/89 (2.2) | 2/101 (2.0) | 4/89 (4.5) | 13/340 (3.8) |
> 10 × ULN | 1/134 (0.7) | 1/101 (1.0) | 0 | 2/101 (2.0) | 1/89 (1.1) | 7/340 (2.1) |
Hemoglobin | ||||||
< LLN | 9/126 (7.1) | 7/98 (7.1) | 12/84 (14.3) | 11/98 (11.2) | 18/84 (21.4) | 44/312 (14.1) |
< 10 mg/dL | 0 | 0 | 1/89 (1.1) | 1/100 (1.0) | 1/89 (1.1) | 3/339 (0.9) |
< 8 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 |
Neutrophils < 1000 cells/mm3 | 0 | 0 | 0 | 0 | 1/89 (1.1) | 1/340 (0.3) |
Lymphocytes < 500 cells/mm3 | 0 | 0 | 2/89 (2.2) | 0 | 2/89 (2.2) | 2/340 (0.6) |
Platelets > 600 billion/L | 0 | 2/101 (2.0) | 0 | 4/101 (4.0) | 0 | 7/339 (2.1) |
Patients with any postbaseline elevation in ALT, n/N (%) | ||||||
≥ 3 × ULN | 0 | 0 | 0 | 0 | 2/89 (2.1) | 4/340 (1.2) |
≥ 5 × ULN | 0 | 0 | 0 | 0 | 0 | 0 |
≥ 10 × ULN | 0 | 0 | 0 | 0 | 0 | 0 |