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 Supplementary Information The online version contains supplementary material available at 10.1007/s40257-020-00583-3.

Laboratory Safety of Dupilumab in Patients Aged 6–11 Years with Severe Atopic Dermatitis: Results from a Phase III Clinical Trial

“…Dupilumab + TCS-associated decreases in platelet counts and LDH were similar to those reported in adolescents and may represent improvements in AD-associated inflammation. These findings are consistent with outcomes previously reported in adolescents and adults with moderateto-severe AD [16,17], support the pivotal efficacy and safety data previously reported for this clinical trial [15], and echo the observed trends in minor laboratory differences seen in adolescents and adults treated with this biologic agent [16,17]. Together with the results of previous studies in adults and adolescents, these data provide support that dupilumab does not require routine laboratory monitoring before initiation or during treatment in children aged 6-11 years with severe AD.…”

“…Mean platelet counts decreased, but remained within normal range, in both dupilumab + TCS groups, most likely reflecting diminished acute phase reactant activity linked to AD severity [ 21 , 22 ]. Similar trends were seen in previous studies in adults [ 16 ] and adolescents [ 17 ], also without adverse clinical implications. AD is a chronic inflammatory condition with a dynamic course characterized by recurrent acute exacerbations, which can cause oscillating levels of acute phase reactants along with chronic elevations of systemic markers of inflammation [ 21 – 24 ].…”

“…There was a trend for a decrease in mean neutrophil counts and a trend for an increase in the number of patients in the dupilumab + TCS groups having Grades 1 and 2 neutropenia at Week 16. Mild increases in mean eosinophil counts were observed in all treatment groups during the treatment period, consistent with previous reports evaluating dupilumab in adults and adolescents with moderate-to-severe AD [ 9 , 16 , 17 ], asthma [ 25 , 26 ], and chronic rhinosinusitis with nasal polyps [ 27 ]. For the placebo and dupilumab q4w groups, these changes were transient, peaking at Week 8 and returning to near baseline by Week 16.…”

“…Dual blockade of IL-4 and IL-13 with dupilumab inhibits the activity of eosinophils and their recruitment to affected tissue, but not their egress from bone marrow (which is regulated by IL-5) [30][31][32][33]. It has been hypothesized that this may result in a transient increase in circulating eosinophils that does not reflect a pathologic process [16,17,30]. There were no clinically meaningful differences observed in most serum chemistry parameters, and no clinically meaningful differences were observed in urinalysis parameters among the treatment groups.…”

“…Clinical trials of dupilumab with or without topical corticosteroids (TCS) in adults and adolescents with moderate-to-severe AD and in children aged 6–11 years with severe AD have shown significant improvement in signs and symptoms of AD and patient quality of life with dupilumab treatment, with an acceptable safety profile [ 9 – 15 ]. No clinically significant adverse changes in laboratory parameters in adults and adolescents were attributable to dupilumab, supporting its use for treatment of moderate-to-severe AD without routine laboratory monitoring [ 16 , 17 ]. To characterize the impact of dupilumab on laboratory findings in children, we analyzed the laboratory safety data from a phase III clinical trial conducted in children aged 6–11 years with severe AD [ 15 ].…”