Dupilumab use is associated with lower all-cause mortality but increased risk of lymphoma in asthma patients

1. When compared with inhaled corticosteroids (ICS) plus long-acting β-agonists (LABA), dupilumab treatment was associated with an increased risk of lymphoma in asthma patients but also led to lower all-cause mortality.

Evidence Rating Level: 2 (Good)

Study Rundown: Dupilumab, an interleukin (IL)-4α receptor monoclonal antibody, was initially approved as a treatment for atopic dermatitis and later used to treat asthma, where it has been shown to improve lung function, reduce reliance on oral corticosteroids, and decrease severe exacerbations. However, recent studies have shown an increased risk of lymphoma, particularly cutaneous T-cell lymphoma (CTCL), in patients with atopic dermatitis receiving dupilumab. 

This population-based cohort study included patients with asthma who initiated dupilumab and those who initiated combination ICS plus LABA between October 2018 and June 2024. These patients were identified from TriNetX, a multicentre network of 114 million people from 92 healthcare organizations in the United States.

Overall, this study found that patients treated with dupilumab were at an increased risk of lymphoma, especially T-cell and natural killer-cell lymphomas. Despite this, dupilumab-treated patients still displayed lower all-cause mortality. This may be because asthma is inherently associated with elevated mortality risk. Future studies are required to understand the pathophysiology of dupilumab-associated lymphoma and elucidate dupilumab’s long-term safety profile.

Click here to read this study in The European Respiratory Journal

Relevant reading: Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study

In-Depth [population-based cohort study]:

It is unclear whether the elevated risk of lymphoma in patients receiving dupilumab for atopic dermatitis is seen in patients receiving it for asthma. This population-based cohort study investigated the incidence of lymphoma in patients with asthma treated with dupilumab compared to those receiving standard combination therapy with ICS plus LABA. The primary outcomes were incidence of lymphoma and its subtypes, incidence of other hematological and non-hematological cancers, and all-cause mortality.

This population-based cohort study compared lymphoma incidence in 14,936 patients (M [SD] age = 46.8 (20.7) years) receiving dupilumab for asthma with 734,126 patients (M [SD] age = 49.9 (21.6) years) receiving ICS plus LABA for asthma. After propensity score matching, 14,900 patients in each group were compared for analysis (dupilumab M [SD] age = 46.8 (20.7) years, 62.3% female; ICS/LABA M [SD] age = 46.4 (22.0) years, 63.0% female). Dupilumab-treated patients were found to have a significantly increased risk of lymphoma compared to ICS/LABA-treated patients (HR 1.79, 95% CI 1.19–2.71), especially T-cell and natural killer (NK)-cell lymphomas (HR 4.58, 95% CI 1.82–11.53). There were no significant differences in the rate of leukemias or malignant solid tumours. However, dupilumab-treated patients had significantly decreased all-cause mortality (HR 0.65, 95% CI 0.57–0.74). 

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