A real-world clinical trial found dupilumab add-on treatment to be effective and safe for severe, uncontrolled asthma, according to study findings published in Respiratory Medicine.
Dupilumab has proven safe and effective for severe, uncontrolled asthma in phase 3 trials. Following up on these results, investigators in The Netherlands sought to evaluate the real-world safety and efficacy of add-on dupilumab for severe, uncontrolled asthma. The primary study outcome was annual exacerbation rate (AER); secondary outcomes were: pulmonary function, as measured by forced expiratory volume in 1 second (FEV1); asthma control questionnaire (ACQ-5) scores; maintenance oral corticosteroid (mOCS) dependency; Asthma-related Quality of Life Questionnaire (AQLQ) score; and frequency of reported adverse events (AEs).
The researchers conducted a retrospective, real-world, single-center, cohort study (ClinicalTrials.gov Identifier: NCT05331755) that included 148 patients with severe, uncontrolled asthma who were treated with add-on dupilumab at the Franciscus Gasthuis & Vlietland hospital, a tertiary referral center in Rotterdam, the Netherlands, between January 2019 and December 2020.
Dupilumab was administered subcutaneously (200mg/14 days) at the hospital or self-administered at home. Patients dependent on mOCS therapy or with other type-2 comorbidities received 300mg/14 days. First injection for all patients was a double dose.
Investigators found that patients’ median baseline AER of 4.00 (IQR, 2.00-5.00) was reduced to 1.00 (IQR, 0.00-2.00) after 12 months of dupilumab add-on treatment (P <.001). The level of mOCS dependency also decreased with add-on dupilumab usage – from 39.9% of patients at baseline to 20.3% of patients after 6 months of add-on dupilumab and to 14.9% at 12 months (P <.001).
Likewise, patients’ median baseline FEV1 of 2.21 (IQR, 1.58-2.85) improved to 2.50 (IQR, 2.00-3.06) at 6 months, and to 2.51 (IQR, 1.88-3.04) at 12 months of add-on dupilumab use (P <.001). Study participants’ median baseline ACQ of 3.00 (IQR, 2.00-3.80) also improved to 1.80 (IQR, 0.60-2.95) at 6 months, and to 1.40 (IQR, 0.20-2.60) at 12 months (P .001).
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This real-world study indicates that dupilumab as add-on therapy for severe asthma leads to an improvement in rate of severe asthma exacerbations, oral corticosteroid dependency, pulmonary function, asthma control and quality of life.
Notably, 45.3% of participants reported at least 1 AE resulting from dupilumab therapy. Headache (23.6%), influenza-like symptoms (15.5%), eye-related symptoms (10.8%), and injection site reactions (10.1%) were the most frequent AEs. Investigators noted 8.8% of participants experienced eosinophilia and 2.7% experienced hyper-eosinophilia in addition to reported AEs. There were 2 deaths during the 12-month follow-up, investigators believe unrelated to dupilumab.
With respect to quality of life, the investigators found that 27% (40/148) of patients had improved median AQLQ scores from baseline to 12 months. Study authors did not report AQLQ score findings for the remaining 108 patients.
Subgroups with high FeNO (≥50 ppb) or eosinophils (≥300/μL) at baseline showed the most benefit in exacerbation reduction and ACQ improvement; however, all patients showed statistically significant improvement in AERs and in ACQ scores. Patients with high FeNO or high eosinophils at baseline also showed the most improvement with respect to FEV1. There was no significant improvement in FEV1 among patients with medium eosinophilic values (≥150 and <300/ μL) (P =.003) and medium FeNO values (≥25 and <50ppb) (P =.001), or among patients with lower eosinophilic or FeNO values.
Study limitations include missing data and data collection delays due to patient difficulties in obtaining spirometry during the pandemic; lack of accounting for the influence of mOCS use and previous biologic use at baseline; recall bias in self-reported AEs; and lack of accounting for the effect of COVID-19-related isolation on AE reductions.
“This real-world study indicates that dupilumab as add-on therapy for severe asthma leads to an improvement in rate of severe asthma exacerbations, oral corticosteroid dependency, pulmonary function, asthma control and quality of life,” the investigators concluded. They further noted that benefits of add-on dupilumab were most substantial for those with high baseline eosinophils and FeNO, and that side-effects of treatment were mild.
Disclosure: This research was supported by Sanofi. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
