In this real-world study, we have provided a comprehensive characterization of patients with asthma initiating treatment with dupilumab in clinical practice. These data come from the patient population participating in RAPID, the first real-world registry of dupilumab initiated in patients with asthma. Patients were between 12 and 85 years of age, predominantly female and non-smokers, and the most prevalent reported race was white. Most patients (86.8%) had moderate-to-severe asthma according to GINA classification [1]. Patients had a mean 20.9 (median: 15.5)-year history since asthma diagnosis and experienced frequent exacerbations, with a mean of 4.4 severe asthma exacerbations reported in the year before enrollment in 78 of 152 patients with available data.

The patients’ mean BMI was elevated at 30.7 kg/m2 (range: 13.9–63.3 kg/m2). It has been shown that an increased BMI is associated with decreased FVC and FEV1 [21]. Obesity is commonly defined as BMI ≥ 30 kg/m2 [22] and is a common comorbidity of asthma [23, 24] that is associated with severity, worse asthma control, and poor response to therapy [23, 25, 26]. Furthermore, sleep-disordered breathing that can affect patients with obesity is also associated with difficult-to-control asthma [27, 28]. The highest proportion of adult patients enrolling in RAPID had a BMI ≥ 30 kg/m2 and the lowest proportion had a BMI < 25 kg/m2. In adolescent patients enrolled in the study, the opposite was observed, with the highest proportion having a BMI < 25 kg/m2 and the lowest proportion of adolescent patients having a BMI ≥ 30 kg/m2.

The population enrolling in the registry had impaired lung function, poor asthma control, and reduced asthma-related quality of life before initiating biologic therapy with dupilumab. These characteristics were expected in patients with moderate-to-severe asthma, the target population as per the dupilumab prescribing information [29]. Unexpectedly, 20.4% of patients (Table 2) presented with less severe asthma based on the GINA classification scores (GINA 1–3). The therapeutic decision to prescribe dupilumab to these patients may have been driven by, for example, persistent symptoms, a high number of exacerbations, or a limited response to maintenance therapy. The presence of multiple, less severe, coexisting type 2 inflammatory conditions could also explain the initiation of dupilumab in this subgroup. This hypothesis is supported by the finding that 85.6% of patients (167/195) had > 1 coexisting type 2 inflammatory condition. However, further data are needed to better understand the reasons to prescribe a biologic for the treatment of asthma in these patients.

With the emergence of personalized medicine over the past decade, the use of biomarkers such as blood eosinophil counts, FeNO levels, or IgE has become a cornerstone in the diagnosis of asthma and in determining optimal treatment [30]. Unexpectedly, biomarker levels were recorded in only approximately one-third of patients enrolled in the RAPID registry, despite being prescribed a biologic. It is worth noting that the study protocol did not include a regular schedule to test blood eosinophil counts and IgE but included guidance to test these as per local standard of care. Taken together, this might suggest that biomarker measurements are not yet widely applied and are often underused in clinical settings. This could be, among other reasons, due to biomarker tests not being easily accessible or a lack of awareness of their utility.

The patients with available biomarker measurements were found to mostly have elevated blood eosinophil counts (median 305.0 cells/μL), with one-third of patients having blood eosinophil counts ≥ 500 cells/μL, and also elevated FeNO levels (Table 4), which is consistent with observations in patient populations with moderate-to-severe asthma. This is also indicative of a type 2 inflammatory phenotype in the enrolled patients, which is representative of the patient populations enrolled in previous dupilumab asthma trials [12,13,14,15]. In terms of asthma severity measured by the number of severe exacerbations in the prior year, this initial patient cohort from RAPID reported approximately twice the number of severe exacerbations (mean 4.4 (Table 5) vs. 2.09) reported in QUEST (13). However, the RAPID cohort reported better baseline lung function than the patients in QUEST.

Smoking is known to negatively impact clinical and therapeutic outcomes of asthma treatments and results in poorer asthma control [31,32,33,34]. However, to avoid potential confusion with chronic obstructive pulmonary disease, smoking is also a main exclusion criterion for patient enrollment in asthma clinical trials, despite approximately 50% of adult patients with asthma reporting that they are currently smoking or have smoked in the past [33]. Incidentally, the number of patients with asthma recorded as smokers in previous real-world studies of biologic therapy for asthma has been reported to range between 0 and 41% in a recent systematic review [35]. At the time of this analysis, 24.4% of patients in RAPID were current or former smokers. The inclusion of this patient population bears importance and may give new insights into asthma control and asthma management in this subpopulation.

Future publications will report on the efficacy and safety of dupilumab in the real-world RAPID registry. Compared to the dupilumab phase 3 clinical trials [13, 14], RAPID allowed the enrollment of patients who were active and former smokers. Additionally, RAPID enrolled patients with a similar burden of severe exacerbations and better lung function, but worse inflammatory biomarkers and more type 2 inflammatory conditions. The presence of type 2 inflammation and/or comorbidities can increase the burden of asthma and worsen disease outcomes [36] but may also predict response to biologics [37]. Therefore, it is important to evaluate their impact in a real-world setting to confirm their relevance when deciding on treatment options.

We acknowledge that the study has some limitations inherent to its design as a registry study, which provides a much less strict treatment environment than controlled clinical trials. It has been shown that race and ethnicity are factors in the prevalence and severity of asthma. Therefore, when interpreting these results, it should be considered that, in this initial analysis of 205 patients enrolled in the study, the patient population lacked diversity: a majority of patients were white and from the USA. However, the study is ongoing (with an estimated completion date in 2025 across 8 countries worldwide and an enrollment target of 700 patients), with the goal of ensuring patient diversity and outcomes that are representative of different patient populations. Another limitation is the reporting of biologics as a prior controller medication in this study, pointing to the variation among physicians regarding the definition of a controller medicine.