There have been multiple reports demonstrating the effectiveness of dupilumab in the treatment of ACD (eTable).12-20 The findings from these studies show that dupilumab can improve recalcitrant dermatitis caused by a broad range of contact allergens, including nickel. This highlights its ability to improve ACD caused by allergens with a TH1 bias, despite its primarily TH2-dampening effects. Notably, several studies have reported successful use of dupilumab for systemic ACD.12,18 In addition, dupilumab may be able to improve symptoms of ACD in as little as 1 to 4 weeks. Unlike some systemic therapies for ACD, dupilumab also benefits from its lack of notable immunosuppressive effects.9 A phase 4 clinical trial at Brigham and Women’s Hospital (Boston, Massachusetts) is recruiting participants, with a primary goal of investigating dupilumab’s impact on ACD in patients who have not improved despite allergen avoidance (ClinicalTrials.gov identifier NCT03935971).
There are a few potential disadvantages to dupilumab. Because it is not yet FDA approved for the treatment of ACD, insurance companies may deny coverage, making it likely to be unaffordable for most patients. Furthermore, the side-effect profile has not been fully characterized. In addition to ocular adverse effects, a growing number of studies have reported face and neck erythema after starting dupilumab. Although the cause is unclear, one theory is that the inhibition of IL-4/IL-13 leads to TH1/TH17 polarization, thereby worsening ACD caused by allergens that activate a TH1-predominant response.21 Finally, not all cases of ACD respond to dupilumab.22
Patch Testing While on Dupilumab
Diagnosing ACD is a challenging process. An accurate history and physical examination are critical, and patch testing remains the gold standard when it comes to identifying the source of the contact allergen(s).
There is ongoing debate among contact dermatitis experts regarding the diagnostic accuracy of patch testing for those on immunomodulators or immunosuppressants, as these medications can dampen positive results and increase the risk for false-negative readings.23 Consequently, some have questioned whether patch testing on dupilumab is accurate or feasible.24 Contact dermatitis experts have examined patch testing results before and after initiation of dupilumab to further investigate. Puza and Atwater25 established that patients are able to mount a positive patch test reaction while on dupilumab. Moreover, a retrospective review by Raffi et al26 found that out of 125 before therapy/on therapy patch test pairs, only 13 were lost after administration of dupilumab. Although this would suggest that dupilumab has little impact on patch testing, Jo et al27 found in a systematic review that patch test reactions may remain positive, change to negative, or become newly positive after dupilumab initiation.
This inconsistency in results may relate to the allergen-specific pathogenesis of ACD—one allergen may have a different response to the mechanism of dupilumab than another.28,29 More recently, de Wijs et al30 reported a series of 20 patients in whom more than two-thirds of prior positive patch test reactions were lost after retesting on dupilumab; there were no clear trends according to the immune polarity of the allergens. This finding suggests that patient-specific factors also should be considered, as this too could have an impact on the reliability of patch test findings after starting dupilumab.29
Final Interpretation
Given its overall excellent safety profile, dupilumab may be a feasible off-label option for patients with ACD that does not respond to allergen avoidance or for those who experience adverse effects from traditional therapies; however, it remains difficult to obtain through insurance because it is not yet FDA approved for ACD. Likewise, its impact on the accuracy of patch testing is not yet well defined. Further investigations are needed to elucidate the pathophysiology of ACD and to guide further use of dupilumab in its treatment.