Dupilumab Improved Asthma Control in Patients With Uncontrolled, Moderate-to-Severe Asthma, Regardless of Exacerbations in the Previous Year

Introduction Dupilumab, a fully human VelocImmune^®-derived anti-interleukin (IL)-4 receptor α monoclonal antibody inhibiting IL-4/IL-13 signaling pathways, key drivers of type 2 inflammation, is approved for treatment of adults with inadequately controlled, moderate-to-severe atopic dermatitis. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), dupilumab 200 mg and 300 mg every 2 weeks compared to matched placebo reduced annualized severe exacerbation rates and improved pre-bronchodilator forced expiratory volume in 1 second (FEV₁), patient-reported outcomes including asthma symptoms and health-related quality-of-life measures, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis was conducted to evaluate the effect of dupilumab on asthma control.

Methods Asthma control was assessed using the 5-item Asthma Control Questionnaire (ACQ-5). Changes in ACQ-5 scores from baseline to Weeks 12, 24, and 52 were analyzed in patients with ≥ 1, ≥ 2, or ≥ 3 severe exacerbations in the previous year.

Results Mean reductions in ACQ-5 scores of ≥ 0.5, indicating clinically meaningful improvement in asthma control, from baseline to Weeks 12, 24, and 52, were observed for both dupilumab doses, regardless of severe exacerbation history in the previous year ([Table 1]). Significant improvement vs. placebo (all P < 0.05) in ACQ-5 scores were noted by Week 12 and maintained over the 52 week treatment period regardless of previous exacerbation history. The most frequent adverse event in the 200 mg and 300 mg dupilumab groups vs. the matched-placebo groups was injection-site reactions (15%/18% vs. 5%/10%).

Tab. 1 Effect of dupilumab vs. placebo on asthma control (ACQ-5)* by history of exacerbations in the year prior to study entry.

	Patients with ≥ 1 severe exacerbation				Patients with ≥ 2 severe exacerbation				Patients with ≥ 3 severe exacerbation
	1.14 mL/200 mg q2w		2 mL/300 mg q2w		1.14 mL/200 mg q2w		2 mL/300 mg q2w		1.14 mL/200 mg q2w		2 mL/300 mg q2w
	Placebo (n = 317)	Dupilumab (n = 631)	Placebo (n = 321)	Dupilumab (n = 633)	Placebo (n = 167)	Dupilumab (n = 291)	Placebo (n = 177)	Dupilumab (n = 303)	Placebo (n = 76)	Dupilumab (n = 128)	Placebo (n = 84)	Dupilumab (n = 145)
Baseline ACQ-5 score, mean (SD)	2.71 (0.73)	2.76 (0.80)	2.77 (0.77)	2.77 (0.76)	2.78 (0.76)	2.83 (0.86)	2.83 (0.82)	2.84 (0.79)	2.87 (0.89)	2.98 (0.95)	2.89 (0.90)	2.91 (0.83)
Change from baseline at Week 12	n = 303	n = 605	n = 312	n = 603	n = 157	n = 284	n = 173	n = 289	n = 72	n = 127	n = 81	n = 141
LS mean (SE)	−1.02 (0.06)	−1.36 (0.04)	−1.11 (0.05)	−1.36 (0.04)	−1.13 (0.08)	−1.47 (0.06)	−1.12 (0.07)	−1.43 (0.06)	−1.12 (0.12)	−1.49 (0.09)	−1.06 (0.11)	−1.61 (0.09)
LS mean difference matched placebo (95% CI)		−0.33 (−0.46 to −0.20)		−0.25 (−0.38 to −0.13)		−0.33 (−0.52 to −0.15)		−0.30 (−0.48 to −0.12)		−0.37 (−0.67 to −0.07)		−0.55 (−0.83 to −0.27)
P value vs. matched placebo		< 0.0001		0.0001		0.0005		0.0011		0.0144		0.0001
Change from baseline at Week 24	n = 296	n = 590	n = 297	n = 585	n = 153	n = 280	n = 165	n = 280	n = 67	n = 123	n = 76	n = 133
LS mean (SE)	−1.09 (0.06)	−1.44 (0.04)	−1.21 (0.06)	−1.40 (0.04)	−1.10 (0.08)	−1.54 (0.06)	−1.26 (0.08)	−1.46 (0.06)	−1.11 (0.12)	−1.63 (0.09)	−1.12 (0.11)	−1.64 (0.09)
LS mean difference matched placebo (95% CI)		−0.35 (−0.49 to −0.21)		−0.19 (−0.32 to −0.05)		−0.44 (−0.63 to −0.25)		−0.20 (−0.39 to −0.02)		−0.52 (−0.81 to −0.23)		−0.52 (−0.79 to −0.25)
P value vs. matched placebo		< 0.0001		0.0064		< 0.0001		0.0336		0.0004		0.0002
Change from baseline at Week 52	n = 285	n = 539	n = 283	n = 554	n = 149	n = 251	n = 159	n = 264	n = 66	n = 110	n = 71	n = 129
LS mean (SE)	−1.17 (0.06)	−1.56 (0.04)	−1.31 (0.06)	−1.52 (0.04)	−1.21 (0.08)	−1.66 (0.06)	−1.33 (0.08)	−1.57 (0.06)	−1.30 (0.13)	−1.73 (0.10)	−1.28 (0.12)	−1.71 (0.09)
LS mean difference matched placebo (95% CI)		−0.39 (−0.52 to −0.25)		−0.22 (−0.35 to −0.08)		−0.45 (−0.65 to −0.25)		−0.24 (−0.43 to −0.05)		−0.44 (−0.75 to −0.12)		−0.43 (−0.73 to −0.13)
P value vs. matched placebo		< 0.0001		0.0016		< 0.0001		0.0139		0.0074		0.0050

Conclusion Dupilumab significantly improved asthma control, as measured by the ACQ-5, regardless of prior severe exacerbation history and was generally well tolerated.