Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials

Abstract

Background: Several recent clinical trials have assessed the effects of dupilumab in uncontrolled asthma, but reached no definite conclusion. We therefore conducted this meta-analysis to evaluate the overall efficacy and safety of dupilumab for the treatment of uncontrolled asthma.

Methods: All randomized controlled trials were included. Standard mean differences (SMD) or relative risks (RR) were calculated using Fixed-or random-effects models.

Results: Five studies involving 3369 patients were identified. Pooled analysis showed significant improvements in the first-second forced expiratory volume (FEV₁) (SMD = 4.29, 95% CI: 2.78-5.81) and Asthma Quality of Life Questionnaire scores (SMD = 4.39, 95% CI: 1.44-7.34). Dupilumab treatments were also associated with significantly decreased 5-item Asthma Control Questionnaire scores (SMD = - 4.95, 95% CI: - 7.30 to - 2.60), AM and PM asthma symptom scores (SMD = - 5.09, 95% CI: - 6.40 to - 3.77; SMD = - 4.92, 95% CI: - 5.98 to - 3.86, respectively), and severe exacerbation risk (RR = 0.73; 95% CI: 0.67-0.79) compared with placebo, with similar incidence of adverse events (RR = 1.0; 95% CI: 0.96-1.04).

Conclusion: Dupilumab treatment is relatively well-tolerated and could significantly improve FEV₁, symptoms, asthma control, and quality of life, and reduced severe exacerbation risk in patients with uncontrolled asthma.

Keywords: Dupilumab; Meta-analysis; Randomized control trial; Uncontrolled asthma.

Fig. 1

Flow chart of study identification, inclusion, and exclusion

Fig. 2

Trial sequential analysis of 5 trials comparing dupilumab with placebo for FEV₁. Trial sequential analysis of 7 groups (two trial contains two groups) illustrating that the cumulative z curve crossed both the conventional boundary and the trial sequential monitoring boundary, establishing sufficient and conclusive evidence and suggesting that further trials are not required. Using α = 0.05 (two-sided) and β = 0.20 (power of 80%) calculate that the optimal sample size was 1882 patients

Fig. 3

The effect of dupilumab versus placebo on FEV₁. SD = standard derivation, IV = Inverse Variance, CI = confidence interval, Std. Mean Difference = standardized mean difference

Fig. 4

The effect of dupilumab versus placebo on ACQ-5 score. ACQ-5 = 5-item Asthma Control Questionnaire, SD = standard derivation, IV = Inverse Variance, CI = confidence interval, Std. Mean Difference = standardized mean difference

Fig. 5

The effect of dupilumab versus placebo on FE_NO. FE_{NO =} fractional exhaled nitric oxide SD = standard derivation, IV = Inverse Variance, CI = confidence interval, Std. Mean Difference = standardized mean difference

Fig. 6

The effect of dupilumab versus placebo on AM asthma symptom score

Fig. 7

The effect of dupilumab versus placebo on PM asthma symptom score. SD = standard derivation, IV = Inverse Variance, CI = confidence interval, Std. Mean Difference = standardized mean difference

Fig. 8

The effect of dupilumab versus placebo on AQLQ. AQLQ = Asthma Quality of Life Questionnaire, SD = standard derivation, IV = Inverse Variance, CI = confidence interval, Std. Mean Difference = standardized mean difference

Fig. 9

Forest plot of the effect of dupilumab treatment on asthma severe exacerbations verse placebo. Fixed-effects model. RR = relative risk, CI = confidence interval

Fig. 10

Forest plot of the effect of dupilumab treatment on adverse events verse placebo. Fixed-effects model. RR = relative risk, CI = confidence interval

Fig. 11

Risk of bias summary of included studies summary

Fig. 12

Funnel plot of the included studies evaluated adverse events