Baricitinib, dupilumab see comparable real-world results in atopic dermatitis
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Key takeaways:
- Reductions in Eczema Area and Severity Index scores were rapid and significant.
- There were improvements in circulating eosinophil counts.
- There were differences in gene expression related to Th1 and Th2.
Responses to baricitinib and dupilumab were notable and similar among patients with moderate to severe atopic dermatitis in a real-world setting, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
However, these treatments had distinct impacts on immune responses, Yung-Tsu Cho, MD, PhD, visiting staff, department of dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, and colleagues wrote.
The 76 patients in the study had moderate to severe AD and at least 16 weeks of treatment. The 28 patients (20 males; mean age, 26.1 years) in the baricitinib (Olumiant, Eli Lilly) group received daily doses of 4 mg. The 48 patients (34 males; mean age, 31 years) in the dupilumab (Dupixent; Regeneron, Sanofi) group received a 600 mg loading dose and 300 mg biweekly doses.
Reductions in Eczema Area and Severity Index (EASI) scores were rapid and significant with treatment, the researchers said, and the differences between the groups at all the time points in the study were not significant. Average EASI scores included 6.5 for the baricitinib group and 4.8 for the dupilumab group at 16 weeks.
The groups also had similar proportions of patients who achieved EASI 50, EASI 75, EASI 90 and EASI 100 scores, the researchers continued. At week 16, EASI 50 was achieved by 100% of the dupilumab group and 96.43% of the baricitinib group.
Similarly, at week 16, 79.17% of the dupilumab group and 71.43% of the baricitinib group achieved EASI 75; 52.08% of the dupilumab group and 39.29% of the baricitinib group achieved EASI 90; and 2.08% of the dupilumab group and 0% of the baricitinib group achieved EASI 100.
Additionally, both groups experienced improvements in circulating eosinophil counts after treatment, although the researchers said that significant decreases in serum IgE levels only happened in the dupilumab group.
Dupilumab treatment further yielded notably lower levels of CD30 and eotaxin-3 as well as significantly higher levels of IFN-inducible T-cell alpha chemoattractant, the researchers continued.
With baricitinib treatment, CD30, IL-2R, IFN-gamma, IL-18, IL-22, macrophage-derived chemokine and eotaxin-3 levels all saw significant decreases, the researchers said.
Compared with the baricitinib group, levels of CD30, eotaxini-3 and epithelial neutrophil-activating peptide 78 were significantly lower and levels of IFN-inducible T-cell alpha chemoattractant were significantly higher in the dupilumab group.
These results indicate a more pronounced reduction in T-helper (Th)2 chemokines with dupilumab compared with baricitinib, the researchers said, with a stronger inhibition on Th1 cytokines and chemokines with baricitinib compared with dupilumab.
A comparative RNA sequencing analysis of peripheral blood mononuclear cells also found similar results, the researchers said. Many genes such as IL13, IL17RB, TRPM6 and PBK associated with immune responses exhibited elevated expressions among patients with AD compared with healthy controls, the researchers continued, but this expression decreased with baricitinib and dupilumab treatment.
But the researchers added that the patterns of change between the groups were distinct. The reduction in the expression of IGHE, HRH1 and other genes related to Th2 was more significant in the dupilumab group, they said, whereas the reduction in the expression of TNFRSF18, TNFRSF6B, IRF and other genes related to Th1 was greater in the baricitinib group.
Baricitinib’s efficacy was comparable with its performance in previous studies, the researchers continued, with more favorable responses based on EASI score improvements and EASI 75 and EASI 90 results compared with clinical responses.
The researchers also said that baricitinib and dupilumab had distinct effects in modulating systemic immune responses at the protein and mRNA levels. In Th1 responses, baricitinib had more robust inhibitory activity. In Th2 responses, dupilumab had similar or slightly greater reductions.
Further, the researchers said the disparate alterations in serum IgE levels that they saw after treatment between the groups casts additional doubt on what kind of role IgE has in the pathogenesis of AD.
Despite these individual effects on immune responses among patients with moderate to severe AD, the researchers said, responses to baricitinib and dupilumab were both notable and comparable. These results also may indicate which treatment may be more effective for specific patients with AD, the researchers added, for personalized care.
Perspective
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The data from this study are intriguing, as they add to the growing body of evidence showing that while at a population level efficacy can seem similar between our newer systemic AD therapies, molecularly and immunologically, there may be subtle differences following treatment. Whether these differences in IgE levels or traditional type 1 or type 2 inflammatory markers have functional consequences for longer term safety, efficacy or comorbidities remains to be seen, and additional longitudinal studies are needed to best match the right patient to the right therapy. For now, the authors’ approach of patient-directed choice-based balanced discussion of risk and benefits remains our best strategy when it comes to systemic therapy in AD.
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