Systemic immunosuppressant medications used for atopic dermatitis (AD), such as cyclosporine, methotrexate, and other immunosuppressants, require baseline and serial blood tests. |
Previous analyses from randomized, double-blinded, placebo-controlled trials in adults with moderate-to-severe AD have shown that dupilumab (a monoclonal antibody that specifically blocks the shared receptor component for interleukin-4 and interleukin-13) did not result in any clinically meaningful changes in laboratory parameters for hematology, serum chemistry, and urinalysis. |
An analysis of laboratory parameters from a similar randomized, double-blinded, placebo-controlled trial of dupilumab in adolescents with moderate-to-severe AD identified only clinically insignificant transient eosinophilia and decreases in lactate dehydrogenase, supporting use of dupilumab in this age group without routine laboratory monitoring for hematology, serum chemistry, and urinalysis. |
1 Introduction
2 Methods
2.1 Study Design, Patients, and Treatment
2.2 Ethics
2.3 Laboratory Measurements
Parameters investigated | Reported units |
---|---|
Hematology | |
Red blood cell | |
Mean corpuscular hemoglobin concentration | g/dL |
Mean corpuscular hemoglobin | pg |
Mean corpuscular volume | fL |
Erythrocytes | × 1012/L |
Hematocrit | % |
Hemoglobin | g/L |
Platelets | |
Platelets | × 109/L |
White blood cells | |
Basophils | × 109/L |
Basophils/leukocytes | % |
Eosinophils | × 109/L |
Eosinophils/leukocytes | % |
Leukocytes | × 109/L |
Lymphocytes | × 109/L |
Lymphocytes/leukocytes | % |
Monocytes | × 109/L |
Monocytes/leukocytes | % |
Neutrophils | × 109/L |
Neutrophils/leukocytes | % |
Serum chemistry parameters | |
Renal function | |
Blood urea nitrogen | mmol/L |
Creatinine | μmol/L |
Urate | μmol/L |
Liver function | |
ALT | U/L |
ALP | U/L |
AST | U/L |
Bilirubin | μmol/L |
Direct bilirubin | μmol/L |
Indirect bilirubin | μmol/L |
LDH | U/L |
Electrolytes | |
Bicarbonate | mmol/L |
Calcium | mmol/L |
Chloride | mmol/L |
Potassium | mmol/L |
Sodium | mmol/L |
Metabolic function | |
Albumin | g/L |
CPK | U/L |
Glucose | mmol/L |
Protein | g/L |
Lipids | |
Cholesterol | mmol/L |
HDL | mmol/L |
LDL | mmol/L |
Triglycerides | mmol/L |
Urinalysis | |
Specific gravity | n/a |
Urine pH | n/a |
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The test result was associated with accompanying symptoms.
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The test result required additional diagnostic testing or medical/surgical intervention.
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The test result prompted dose adjustment (outside of those stipulated by the protocol) and/or discontinuation from the study.
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Management of the event required significant additional concomitant drug treatment or other therapy.
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Neutrophils ≤ 0.5 × 109/L, platelets ≤ 50 × 109/L
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ALT and/or AST > 3 × ULN with total bilirubin > 2 × ULN (unless the elevated bilirubin levels were related to confirmed Gilbert’s syndrome)
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Confirmed AST and/or ALT > 5 × ULN persisting > 2 weeks
2.4 Statistical Analysis
3 Results
3.1 Patients
Primary system organ class TEAE by MedDRA PT | Placebo (n = 85) | Dupilumab 200/300 mg q2w (n = 82) | Dupilumab 300 mg q4w (n = 83) |
---|---|---|---|
Number of patients with ≥ 1 laboratory abnormalities reported as TEAEs, n (%) | 4 (4.7) | 2 (2.4) | 4 (4.8) |
Blood and lymphatic system disorders, n (%) | 1 (1.2) | 0 | 0 |
Anemia | 1 (1.2)a | 0 | 0 |
Investigations, n (%) | 2 (2.4) | 2 (2.4) | 3 (3.6) |
Blood creatine phosphokinase increased | 1 (1.2) | 1 (1.2) | 2 (2.4) |
Eosinophil count increased | 0 | 0 | 1 (1.2)b |
Transaminases increased | 1 (1.2)c | 1 (1.2)d | 0 |
Liver function test increased | 1 (1.2)e | 0 | 0 |
Metabolism and nutrition disorders, n (%) | 0 | 0 | 1 (1.2) |
Hyperuricemia | 0 | 0 | 1 (1.2)f |
Renal and urinary disorders, n (%) | 1 (1.2) | 0 | 0 |
Proteinuria | 1 (1.2)g | 0 | 0 |
3.2 Clinical Laboratory Parameters Reported During the Treatment Period
3.2.1 Hematology
3.2.1.1 Red Blood Cells and Platelets
Time point | Grade | Placebo (n = 85) | Dupilumab 200 mg/300 mg q2w (n = 82) | Dupilumab 300 mg q4w (n = 83) |
---|---|---|---|---|
Baseline | Grade 1 (mild): 75 × 109/L to < LLN | 2/83 (2.4) | 0/82 | 1/82 (1.2) |
Grade 2 (moderate): 50 × 109/L to < 75 × 109/L | 0/83 | 0/82 | 0/82 | |
Grade 3 (severe): 25 × 109/L to < 50 × 109/L | 0/83 | 0/82 | 0/82 | |
Grade 4 (potentially life-threatening): < 25 × 109/L | 0/83 | 0/82 | 0/82 | |
Week 4 | Grade 1 (mild): 75 × 109/L to < LLN | 1/75 (1.3) | 0/78 | 1/78 (1.3) |
Grade 2 (moderate): 50 × 109/L to < 75 × 109/L | 0/75 | 0/78 | 0/78 | |
Grade 3 (severe): 25 × 109/L to < 50 × 109/L | 0/75 | 0/78 | 0/78 | |
Grade 4 (potentially life-threatening): < 25 × 109/L | 0/75 | 0/78 | 0/78 | |
Week 8 | Grade 1 (mild): 75 × 109/L to < LLN | 2/73 (2.7) | 0/75 | 1/76 (1.3) |
Grade 2 (moderate): 50 × 109/L to < 75 × 109/L | 0/73 | 0/75 | 0/76 | |
Grade 3 (severe): 25 × 109/L to < 50 × 109/L | 0/73 | 0/75 | 0/76 | |
Grade 4 (potentially life-threatening): < 25 × 109/L | 0/73 | 0/75 | 0/76 | |
Week 16 | Grade 1 (mild): 75 × 109/L to < LLN | 1/69 (1.4) | 1/74 (1.4) | 0/77 |
Grade 2 (moderate): 50 × 109/L to < 75 × 109/L | 0/69 | 0/74 | 0/77 | |
Grade 3 (severe): 25 × 109/L to < 50 × 109/L | 0/69 | 0/74 | 0/77 | |
Grade 4 (potentially life-threatening): < 25 × 109/L | 0/69 | 0/74 | 0/77 |
3.2.1.2 White Blood Cells
Time point | Grade | Placebo (n = 85) | Dupilumab 200 mg/300 mg q2w (n = 82) | Dupilumab 300 mg q4w (n = 83) |
---|---|---|---|---|
Baseline | Grade 1 (mild): 0.50 × 109/L to 1.50 × 109/L | 39/85 (45.9) | 39/82 (47.6) | 45/83 (54.2) |
Grade 2 (moderate): > 1.50 × 109/L to 5.00 × 109/L | 13/85 (15.3) | 10/82 (12.2) | 9/83 (10.8) | |
Grade 3 (severe): > 5.00 × 109/L | 0/85 | 0/82 | 0/83 | |
Week 4 | Grade 1 (mild): 0.50 × 109/L to 1.50 × 109/L | 32/78 (41.0) | 39/81 (48.1) | 38/79 (48.1) |
Grade 2 (moderate): > 1.50 × 109/L to 5.00 × 109/L | 12/78 (15.4) | 9/81 (11.1) | 7/79 (8.9) | |
Grade 3 (severe): > 5.00 × 109/L | 0/78 | 1/81 (1.2) | 0/79 | |
Week 8 | Grade 1 (mild): 0.50 × 109/L to 1.50 × 109/L | 35/76 (46.1) | 34/76 (44.7) | 29/78 (37.2) |
Grade 2 (moderate): > 1.50 × 109/L to 5.00 × 109/L | 9/76 (11.8) | 15/76 (19.7) | 15/78 (19.2) | |
Grade 3 (severe): > 5.00 × 109/L | 0/76 | 1/76 (1.3) | 1/78 (1.3) | |
Week 16 | Grade 1 (mild): 0.50 × 109/L to 1.50 × 109/L | 36/72 (50.0) | 32/74 (43.2) | 30/78 (38.5) |
Grade 2 (moderate): > 1.50 × 109/L to 5.00 × 109/L | 5/72 (6.9) | 10/74 (13.5) | 10/78 (12.8) | |
Grade 3 (severe): > 5.00 × 109/L | 0/72 | 1/74 (1.4) | 0/78 |
Time point | Grade | Placebo (n = 85) | Dupilumab 200 mg/300 mg q2w (n = 82) | Dupilumab 300 mg q4w (n = 83) |
---|---|---|---|---|
Baseline | Grade 1 (mild): 1.5 × 109/L to < LLN | 1/85 (1.2) | 1/82 (1.2) | 0/83 |
Grade 2 (moderate): 1.0 × 109 to < 1.5 × 109/L | 0/85 | 1/82 (1.2) | 0/83 | |
Grade 3 (severe): 0.5 × 109/L to < 1.0 × 109/L | 0/85 | 0/82 | 0/83 | |
Grade 4 (potentially life-threatening): < 0.5 × 109/L | 0/85 | 0/82 | 0/83 | |
Week 4 | Grade 1 (mild): 1.5 × 109/L to < LLN | 2/78 (2.6) | 1/81 (1.2) | 1/79 (1.3) |
Grade 2 (moderate): 1.0 × 109/L to < 1.5 × 109/L | 0/78 | 0/81 | 0/79 | |
Grade 3 (severe): 0.5 × 109/L to < 1.0 × 109/L | 0/78 | 0/81 | 0/79 | |
Grade 4 (potentially life-threatening): < 0.5 × 109/L | 0/78 | 0/81 | 0/79 | |
Week 8 | Grade 1 (mild): 1.5 × 109/L to < LLN | 0/76 | 1/76 (1.3) | 0/78 |
Grade 2 (moderate): 1.0 × 109/L to < 1.5 × 109/L | 1/76 (1.3) | 2/76 (2.6) | 0/78 | |
Grade 3 (severe): 0.5 × 109/L to < 1.0 × 109/L | 0/76 | 0/76 | 1/78 (1.3) | |
Grade 4 (potentially life-threatening): < 0.5 × 109/L | 0/76 | 0/76 | 0/78 | |
Week 16 | Grade 1 (mild): 1.5 × 109/L to < LLN | 1/72 (1.4) | 0/74 | 0/78 |
Grade 2 (moderate): 1.0 × 109/L to < 1.5 × 109/L | 0/72 | 0/74 | 1/78 (1.3) | |
Grade 3 (severe): 0.5 × 109/L to < 1.0 × 109/L | 0/72 | 0/74 | 0/78 | |
Grade 4 (potentially life-threatening): < 0.5 × 109/L | 0/72 | 0/74 | 0/78 |