Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized, Placebo-Controlled, Phase 3 Clinical Trial

Abstract

Background: Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring.

Objective: The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial.

Methods: Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters.

Results: Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant.

Conclusion: No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment.

Trial registration: ClinicalTrials.gov: NCT03054428. Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB).

Conflict of interest statement

Elaine C. Siegfried: Dermavant, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Inc., Verrica—consultant; GlaxoSmithKline, LEO Pharma, Novan, Pfizer—data and safety monitoring board; Eli Lilly, Janssen, Regeneron Pharmaceuticals, Inc., Stiefel, Verrica—Principal Investigator in clinical trials. Thomas Bieber: AbbVie, Almirall, AnaptysBio, Arena, Asana Biosciences, Astellas, BioVersys, Boehringer Ingelheim, Daichi Sankyo, Davos Biosciences, Dermavant/Roivant Sciences, DS Pharma, Eli Lilly, Evaxion Biotech, FLX Bio, Galapagos/MorphoSys, Galderma, Glenmark, GlaxoSmithKline, Incyte, Kymab, LEO Pharma, L´Oréal, Menlo Therapeutics, Novartis, Pfizer, Pierre Fabre, Sanofi/Regeneron Pharmaceuticals, Inc., UCB—lecturer and/or consultant. Eric L. Simpson: AbbVie, Celgene, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Tioga—grants; AbbVie, Boehringer Ingelheim, Dermavant, Dermira, Eli Lilly, Forte Bio, Incyte, LEO Pharma, MedImmune, Menlo Therapeutics, Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron Pharmaceuticals, Inc., Sanofi, Valeant—personal fees. Amy S. Paller: AbbVie, AnaptysBio, Celgene, Eli Lilly, Galderma, Incyte, KrystalBio, LEO Pharma, Janssen, Novartis, Regeneron Pharmaceuticals, Inc.—investigator; AbbVie, Abeona Therapeutics, Almirall, Amgen, Asana Biosciences, Boehringer Ingelheim, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Sol Gel, UCB—consultant with honorarium. Lisa A. Beck: AbbVie, Allakos, Arena Pharma, AstraZeneca, BenevolentAI, Connect Biopharma, Eli Lilly, Incyte, LEO Pharma, Novartis, Pfizer, Principia Biopharma, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Vimalan—consultant. AbbVie, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi—investigator; 3M, Gilead, Medtronics, Moderna—owns stocks. Mark Boguniewicz: Regeneron Pharmaceuticals, Inc.—investigator; Regeneron Pharmaceuticals, Inc., Sanofi Genzyme—consultant. Lynda C. Schneider: Regeneron Pharmaceuticals, Inc., DBV Technologies—investigator; Genentech—research support; AbbVie—consultant. Faisal A. Khokhar, Zhen Chen, Paola Mina-Osorio, Ashish Bansal: Regeneron Pharmaceuticals, Inc.—employees and shareholders. Randy Prescilla: Sanofi Genzyme—employee, may hold stock and/or stock options in the company.

Figures

Fig. 1

Hematology. a Mean change from baseline over time in erythrocytes. b Mean change from baseline over time in platelets. c Mean change from baseline over time in leukocytes. d Mean change from baseline over time in eosinophils. e Median change from baseline over time in eosinophils. f Box plots of absolute eosinophil count over time. Horizontal lines represent medians and X represent means. Error bars show minimum and maximum values. The expanded inset on the right shows a zoom in between 0.0 and 1.4. The dashed red line represents the upper limit of normal. g Mean change from baseline over time in neutrophils. IQR interquartile range, q2w every 2 weeks, q4w every 4 weeks, SD standard deviation

Fig. 2

Serum chemistry. a Mean change from baseline over time in LDH. b Mean change from baseline over time in ALP. c Mean change from baseline over time in ALT. ALP alkaline phosphatase, ALT alanine aminotransferase, LDH lactate dehydrogenase, q2w every 2 weeks, q4w every 4 weeks, SD standard deviation