Dupilumab reduces length, frequency of hospital stays for patients with atopic dermatitis
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Adults with moderate-to-severe atopic dermatitis treated with dupilumab had fewer and shorter hospitalizations related to the skin condition, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
“There were several points of interest regarding the impact of dupilumab on hospitalization,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor, director of clinical research and director of patch testing in the department of dermatology at George Washington University School of Medicine and Health Sciences, told Healio.
“We know that some patients with atopic dermatitis (AD) can have severe refractory disease, rapid-onset severe flares, infections and mental health disturbances that can lead to hospitalization,” Silverberg said.
Successful treatment of AD with dupilumab (Dupixent, Regeneron/Sanofi) could secondarily reduce the risk for hospitalization for these various indications, Silverberg continued, although no one had looked at whether dupilumab could reduce hospitalizations before.
“I was particularly interested in examining hospitalization as a treatment outcome for two reasons. First, hospitalization is often examined in clinical trials of AD treatments as a safety outcome. That is, even highly effective treatments, such as oral immunosuppressive therapy, could lead to serious adverse events requiring hospitalization,” Silverberg said.
Previously, hospitalization had never been seen as an efficacy outcome measure, he continued.
“Indeed, it is a very important outcome measure because it reflects the combined effects of disease flares and sequelae and serious adverse events from treatment,” he said.
Second, Silverberg called hospitalization a very important outcome in health services research because it is associated with markedly higher health care costs and poorer patient outcomes.
“An enormous amount of research has been performed over the past few decades aimed at reducing hospital admissions and readmissions globally,” he said. “The ability of a treatment to reduce costly hospitalizations offers previously unrecognized cost savings from the treatment.”
The researchers reviewed data from seven placebo-controlled phase 2 or phase 3 randomized controlled trials conducted across 28 countries.
The studies included 1,841 patients (median age, 38 years; 59.5% men; 72.1% white) with moderate-to-severe AD treated with 300 mg of dupilumab every 1 or 2 weeks for 12, 16 or 52 weeks, and 1,091 control patients (median age, 38 years; 57.1% men; 70.9% white) treated with placebo.
According to the data, there were 31 hospitalization events among the combined dupilumab group and 46 in the control group, and most of these patients had single hospitalizations.
When researchers evaluated all patients who received dupilumab regardless of whether they received weekly or biweekly doses, they found that those who received the drug had lower rates of all-cause hospitalizations (3.8 vs. 9 events per 100 person-years; RR = 0.38; 95% CI, 0.23-0.62) and AD-related hospitalizations (1 vs. 4.1 events per 100 person-years; RR = 0.21; 95% CI, 0.09-0.51) compared with patients who received placebo.
The most common reason for hospitalization in the combined dupilumab vs. control groups was AD exacerbation, with a 71% risk reduction observed in the dupilumab group (0.7 vs. 2.6 events per 100 patient-years; RR = 0.29; 95% CI, 0.11-0.75).
Other causes for hospitalization also were less frequent in the combined dupilumab group (3.1 vs. 6.5 events per 100 patient-years; RR = 0.47; 95% CI, 0.26-0.85) and included skin and soft-tissue infections (0.5 vs. 0.8 events per 100 patient-years; RR = 0.62; 95% CI, 0.16-2.48).
Also, patients treated with dupilumab experienced shorter overall durations of AD-related hospitalizations compared with the control patients (8.6 vs. 38.9 days per 100 patient-years; RR = 0.1; P = .06).
Compared with the control group, individual dupilumab dose regimens were associated with reduced durations of AD-related hospitalizations for both biweekly doses (10.9 vs. 38.9 days per 100 patient-years; RR = 0.45; 95% CI, 0.07-3.09) and weekly doses (7.3 vs. 38.9 days per 100 patient-years; RR = 0.02; 95% CI, 0-0.16). Both dose regimens also showed reductions in all-cause hospitalizations and AD-related hospitalizations.
“The results are what I expected overall,” Silverberg said. “However, when we began the study, we were a little concerned that the results might not be significant, given that hospitalization is generally a rare outcome. In fact, dupilumab treatment resulted in highly significant reductions of all-cause and AD-related hospitalizations and shorter AD-related hospitalization.”
The researchers noted that bacterial colonization and infection are common causes of AD exacerbations. Also, poor disease control and flaring increase the risks for secondary skin infections. AD has been associated with immune dysregulation as well.
Dupilumab reduces these infectious episodes, the researchers wrote, probably by locally reducing inflammation and improving the skin barrier and by systematically downregulating T-helper type 2-driven inflammation.
“The results illustrate that a highly effective therapy for AD not only improves the eczematous lesions and itch, but also can reduce the mental health burden, skin infections and many other downstream negative sequelae of AD,” Silverberg said.
“The results also underscore the excellent real-world safety profile of dupilumab shown to date,” he added. “Not only did it not increase infections or mental health problems, but it also decreased them enough to be able to detect significant reductions in hospitalizations among patients with AD.”
Next, Silverberg said he would like to see studies with other therapeutics examine hospitalization as an efficacy or combined efficacy-safety outcome.
“I would also like to see next-generation cost-effectiveness models properly incorporate reduced hospitalization,” he said.
For more information:
Jonathan I. Silverberg, MD, PhD, MPH, can be reached at jonathanisilverberg@gmail.com.
Perspective
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AD is more than just itchy skin. It is a systemic disease that significantly impacts patients’ quality of life. In addition to pain, pruritus and decreased sleep, patients with AD are impacted by absenteeism and presenteeism at school and work, increased health care costs and increased risk for cutaneous infections that may become systemic. Infections and severe AD flares may require inpatient hospitalization.
Previous studies have demonstrated that dupilumab significantly clears skin and decreases itching as supported by decreases in Eczema Area and Severity Index, Validated Investigator Global Assessment and peak pruritus numerical rating scale.
This study examined all-cause hospitalizations, AD-related hospitalizations (including admissions for skin infections and AD flares) and duration of AD-related hospital stays with dupilumab vs. controls. Researchers showed that dupilumab also reduces all-cause and AD-related hospitalizations in adults with moderate-to-severe AD and shortens duration of AD-related hospitalizations.
Patients with AD are at increased risk for cutaneous infections and secondary invasive infections due to impaired skin barrier function, altered skin microbiome and pH and immune dysregulation. Patients in this study’s dupilumab group had 38% fewer admissions for skin and soft tissue infections than the control group.
The authors postulate that dupilumab decreases infections via both local and systemic actions: locally by improving the skin barrier and decreasing inflammation and systemically by downregulating T-helper type 2 inflammation.
Some other systemic immunosuppressive therapies for AD may increase the risk for infection. Dupilumab does not increase the risk for infections and, as this study shows, decreases the risk for skin and soft tissue infections severe enough to require hospitalization.
This may be useful practically for those of us who face hurdles getting dupilumab coverage approved for our patients, as many third-party payers require first trying a systemic immunosuppressive therapy before approving dupilumab.
In my practice, we can often get dupilumab approved without first using a systemic immunosuppressive therapy, but not without investing significant clinic resources and physician time writing appeal letters and participating in peer-to-peer calls. I plan on using this study to support my arguments against first using systemic immunosuppressive therapy in my patients.
In addition, by decreasing frequency and duration of AD-related hospitalizations, dupilumab decreases health care costs and utilization among patients with moderate-to-severe AD, another point I will use to help my patients gain expedited coverage of dupilumab therapy.
Some patients are hesitant to start biologic therapies due to concerns about safety. The reduction in all-cause hospitalization in the dupilumab vs. control patients in this study supports dupilumab’s safety profile, and I plan to add this to my discussions with patients who have questions about the safety of this therapy.
In addition to clearer skin and decreased pruritus, dupilumab safely offers patients decreased risk for hospitalization due to AD flares and skin and soft tissue infections as well as the potential for decreased health care costs through decreased resource utilization.
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