Dupilumab Therapy and the Risk of Developing Cutaneous T-Cell Lymphoma in Patients With Atopic Dermatitis
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Dupilumab, a human monoclonal antibody targeting the IL4 alpha receptor, is used for treatment of moderate to severe atopic dermatitis (AD). Previous studies have reported diagnoses of cutaneous T cell lymphoma (CTCL) after dupilumab use.
OBJECTIVE
Investigate the risk of CTCL after dupilumab use in patients with AD.
METHODS
Using the TrinetX database, incidence of cutaneous and lymphoid malignancies including CTCL was compared between a cohort of patients with AD who used dupilumab and a cohort of patients with AD who never used dupilumab. A second analysis excluding prior DMARD use was performed. Propensity score matching was performed to control for covariates.
RESULTS
An increased risk of CTCL was found in the cohort of AD patients who used dupilumab (OR 4.1003, 95% CI 2.055-8.192). The increased risk persisted after exclusion of prior DMARD use. Risk was not increased for other cutaneous or lymphoid malignancies. Most (27/41) cases of CTCL were diagnosed more than one year after dupilumab use.
LIMITATIONS
There is potential for misclassification in the database. Severity of atopic dermatitis could not be assessed. Association between dupilumab and CTCL does not prove causality.
CONCLUSION
Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.
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Additional Info
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Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: a retrospective cohort study
J Am Acad Dermatol 2024 Apr 06;[EPub Ahead of Print], I Hasan, L Parsons, S Duran, Z ZinnFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
In the years after receiving FDA approval for treatment of atopic dermatitis (AD) in patients as young as 1 year of age, dupilumab has become a mainstay in dermatologists’ pharmacologic armamentarium. Dupilumab treats AD by acting on the T-helper type 2 (Th2) signaling pathway. By targeting the IL-4α receptor and creating a heterodimer with the IL-13α receptor, dupilumab inhibits the activity of IL-4 and IL-13, key cytokines that augment Th2 cell differentiation and maturation of dendritic cells while diminishing Th1 activation.1 Despite a largely positive-side effect profile, dupilumab has been associated with the development of cutaneous T-cell lymphoma (CTCL) and atypical lymphoid reactions in rare instances.2-8
Hasan et al recently explored this potential association in their study by comparing the incidence of CTCL between patients with AD who were treated with and without dupilumab.9 After extracting data from 60 healthcare associations (excluding patients who had a pre-existing diagnosis of lymphoma, melanoma, squamous cell carcinoma, or basal cell carcinoma [BCC]) and performing propensity score matching in both cohorts, a total of 22,888 patients with AD treated with dupilumab were compared against 22,871 patients who were not treated with dupilumab. Patients treated with dupilumab had a higher risk of developing CTCL (OR, 4.1003; 95% CI, 2.055–8.192) but had a lower risk of developing melanoma and BCC. An additional analysis was conducted among patients with CTCL who had prior exposure to disease-modifying antirheumatic drugs; the risk persisted even after excluding this subset of patients.
Hasan et al’s work adds to the growing body of literature highlighting the potential association between dupilumab use and the development of CTCL; however, the mechanism by which this occurs and the causality remain unclear. CTCL can be an elusive diagnosis, often requiring numerous biopsies before being captured on histopathology. Moreover, T-cell gene rearrangement, an ancillary study used to identify CTCL, is often equivocal in cases of dupilumab-related CTCL.2 A subset of patients with CTCL may be misdiagnosed with eczema, and subsequent exposure to dupilumab to treat the presumptive eczema may unmask previously smoldering disease. Hasan et al highlighted that 9 of 41 patients with CTCL were diagnosed within 6 months of initiation of dupilumab therapy, suggesting that these might have been unmasked cases. Some speculate that the blockade of the IL-13α2 subunit receptor may hasten the development of CTCL.2,3 Dupilumab can also trigger atypical lymphoid reactions in patients with biopsy-proven AD that shift from an inflammatory to a neoplastic pattern within 9 months (on average) after initiating therapy.7
Taken together, the current literature emphasizes the importance of maintaining CTCL as part of the differential for treatment-refractory eczema, the potential benefit of interval biopsy before and during treatment with dupilumab in the event that the morphology of the patient’s rash changes, and prompt discontinuation of dupilumab if CTCL is suspected. Although these findings do call into question the safety profile of dupilumab, it is worth noting that the number needed to harm as identified by Hasan et al was 738. Instances of dupilumab-associated CTCL remain rare but remarkable.
References