An analysis of three randomized controlled trials suggests that dupilumab is associated with few adverse events and should be considered a safe, viable long-term treatment option for moderate to severe atopic dermatitis (AD) that does not require laboratory monitoring. The findings from this analysis were reported in the British Journal of Dermatology.
Data from three phase 3 trials of dupilumab — LIBERTY AD SOLO 1 (NCT02277743), LIBERTY AD SOLO 2 (NCT02277769), and LIBERTY AD CHRONOS (NCT02260986) — were included in the study. Patients with moderate to severe AD were randomly assigned to dupilumab weekly, every 2 weeks or placebo for either 16 weeks or 52 weeks, depending on the trial. Patients enrolled in the CHRONOS trial were treated with a standardized concomitant topical corticosteroid regimen.
In the SOLO 1 and 2 trials, a total of 456 patients were randomly assigned to placebo every week, 465 patients were randomly assigned to 300 mg dupilumab once every 2 weeks, and 455 patients were randomly assigned to 300 mg dupilumab every week, all for a total of 15 weeks. The CHRONOS trial randomly assigned 315 patients to placebo every week, 110 patients to 300 mg dupilumab once every 2 weeks plus topical corticosteroids, and 315 patients to 300 mg dupilumab every week plus topical corticosteroids, all for a total of 52 weeks. In the analysis of these three trials, researchers assessed safety outcomes as well as changes in several laboratory variables, including hematocrit, hemoglobin, red blood cells, white blood cells, and red cell indices and platelet count.
Participants in the SOLO trials had greater mean reductions in platelets from baseline to 16 weeks if they were treated with dupilumab every 2 weeks and every week vs placebo (-5.7 x 109/L vs -11.2 x 109/L vs -3.1 x 109/L, respectively). In the CHRONOS trial, dupilumab every 2 weeks and every week were associated with greater changes in platelet counts from baseline to week 52 (-12.9 x 109/L vs -13.1 x 109/L vs -2.2 x 109/L, respectively). The incidence of grade 3 thrombocytopenia across all treatments was <1%.
The SOLO trials found greater reductions in neutrophil values from baseline to 16 weeks with dupilumab vs placebo (−0.1 x 109/L [dupilumab every 2 weeks] vs −0.4 x 109/L [dupilumab every week] vs -0.5 x 109/L [placebo]). Similar results were found for the CHRONOS trial. Transient increases in eosinophils were observed among dupilumab-treated patients in the SOLO trials at week 4; however, eosinophils returned close to baseline levels by week 16. No increases in eosinophils were observed in the CHRONOS trial. Similar to the thrombocytopenia incidence rate, the incidence of grade 3 eosinophilia was <1% in dupilumab- and placebo-treated patients.
All trials observed reductions in levels of lactate dehydrogenase from baseline with dupilumab. There were no clinically meaningful changes in any treatment group in terms of other hematology, chemistry, or urinalysis variables.
Limitations of the analysis included the relatively small sample size as well as the exclusion of patients with serious concomitant health conditions, thereby limiting generalizability of the data across the real-world setting.
The researchers concluded that longer-term studies and real-word evidence “will provide additional valuable information on the role of laboratory monitoring in dupilumab-treated patients with AD.”
Disclosure: This clinical trial was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Wollenberg A, Beck LA, Blauvelt A, et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS) [published online August 13, 2019]. Br J Dermatol. doi:10.1111/bjd.18434