Dupilumab improves concurrent asthma, sinonasal outcomes in AD
Treatment with the human monoclonal antibody dupilumab led to improved asthma and sinonasal outcomes occurring concurrently with atopic dermatitis (AD), according to the results of a pooled analysis of four phase 3 trials* presented at ISDS 2018.
The pooled cohort included individuals with comorbid moderate-to-severe AD and not well-controlled asthma, with baseline ACQ-5** scores of ≥0.5 or ≥1 (18.9 percent and 14.3 percent of participants, respectively). Participants were given subcutaneous dupilumab 300 mg Q2W (n=137 and 102 for ACQ-5 ≥ 0.5 and ≥1, respectively) or QW (n=149 and 111, respectively), or placebo (n=177 and 137, respectively). [ISDS 2018, abstract 57]
At week 16, both dupilumab Q2W/QW regimens improved ACQ-5 scores in participants with baseline ACQ-5 ≥0.5 (least squares [LS] mean reduction from baseline, 0.59/0.56 vs 0.27; p=0.0017/p=0.0029) and ACQ-5 ≥1 scores (LS mean reduction from baseline, 0.77/0.74 vs 0.48; p=0.0191/p=0.0312) compared with placebo.
Both dupilumab Q2W/QW also led to significant improvements in EASI*** vs placebo (LS mean percentage reduction from baseline, 78.7 percent/75.9 percent vs 33.9 percent; p<0.0001 for both [ACQ-5 ≥0.5] and 80.2 percent/76.8 percent vs 33.8 percent; p<0.0001 for both [ACQ-5 ≥1]).
Peak pruritus NRS# also improved with dupilumab Q2W/QW vs placebo (LS mean percentage reduction from baseline, 52.0 percent/50.7 percent vs 23.0 percent; p=<0.0001 for both [ACQ-5 ≥0.5] and 51.5 percent/50.6 percent vs 23.9 percent; p=<0.0001 for both [ACQ-5 ≥1]).
Better nasal outcomes
A subgroup evaluation of the pooled analysis demonstrated improved sinonasal outcomes in a cohort of individuals (n=1,171) with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses## (N/PNS), who were given the same dupilumab regimens (n=348/434 for Q2W/QW) or placebo (n=389). [ISDS 2018, abstract 58]
At week 16, SNOT-22### score improved with dupilumab Q2W/QW vs placebo (LS mean reduction from baseline, 9.89/10.83 vs 5.10; p<0.0001 for both).
Similarly, the EASI (LS mean percentage reduction from baseline, 74.9 percent/75.6 percent vs 40.7 percent; p<0.0001 for both) and peak pruritus NRS scores (LS mean percentage reduction from baseline, 50.9 percent/51.4 percent vs 25.8 percent; p<0.0001 for both) remained improved with dupilumab Q2W/QW vs placebo.
Taken together, both analyses showed that dupilumab-treated patients with AD with comorbid asthma and N/PNS achieved clinically significant improvements in all parameters evaluated, said the researchers.
Pink eye effect
Despite the promising efficacy results, the above evaluations reported conjunctivitis as a common adverse event observed with dupilumab, which was consistent with previous reports.
A biomarker analysis showed that dupilumab-related conjunctivitis is marked by intraepithelial goblet cell scarcity in the conjunctival epithelium accompanied by a T-cell and eosinophilic infiltrate in the conjunctival stroma. [ISDS 2018, abstract 48]
Further insight into the functional T-cell profile and activation status of eosinophils is warranted to better elucidate the underlying mechanisms triggering conjunctivitis, given its relatively high rate during dupilumab treatment in patients with AD, said the researchers of this trial.