Efficacy and safety of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults: A pooled analysis of two phase 2 clinical trials

Susan J. Tofte, FNP (Assistant Professor), Kim Papp, MD, PhD (Founder and President), Neil Sadick, MD (Professor), Krista Bohnert, BS (Director of Research), Eric Simpson, MD, MCR (Professor), Diamant Thaçi, MD, PhD (Professor), Thomas Bieber, MD, PhD, MDRA (Professor), Andrew Blauvelt, MD, MBA (President)6 , Howard Sofen, MD (Associate Clinical Professor), Melinda Gooderham, MD (Medical Director), Zhen Chen, PhD (Sr. Manager), Abhijit Gadkari, PhD (Director, Global HEOR), Laurent Eckert, PhD (Director, Global HEOR), Neil M. H. Graham, MD, MPH, MBBS (VP Program Direction), Gianluca Pirozzi, MD, PhD (VP Global), & Marius Ardeleanu, MD (Senior Director Clinical Sciences)​​​​

Journal of the American Association of Nurse Practitioners


Abstract

Background and purpose: There is a need for new treatment options for moderate-to-severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, has recently been approved for this indication.

Methods: A pooled analysis of a phase 2a (NCT01548404) and a phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2 weeks (q2w) in adults with moderate-to-severe AD.

Results: Dupilumab significantly improved clinical outcomes in both analyses at week 12. Itch was significantly improved in the pooled analysis as measured by peak pruritus Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p < .0001 vs. placebo at week 12); similar results were shown for the q2w dose. Dupilumab had an acceptable safety profile.

Conclusions: Consistent with previous studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at week 12, including improvements in itch and sleep loss.

Implications for practice: Subcutaneous dupilumab is an effective new treatment option for adults with moderate-to-severe AD.


Introduction

Skin disorders are the most common types of disease seen by health care professionals and the most frequently reported occupational health problem resulting in absenteeism in the general population (Peate, 2011). Atopic dermatitis (AD), or atopic eczema, is a common chronic inflammatory skin disorder that follows a relapsing course and is characterized by intense itch, disruption of the skin barrier, and type 2/T helper type 2 (Th2) cytokine-mediated inflammation (Eichenfield et al., 2014a Moreno, McPhee, Arruda, & Howell, 2016 Peate, 2011 Ring et al., 2012a). Th2 cytokines are increased in AD lesions and, to a lesser extent, in nonlesional skin (Suárez-Fariñas et al., 2011). Atopic dermatitis is also frequently associated with increased serum immunoglobulin E (IgE) levels and a family or personal history of asthma, allergic rhinitis, or type I allergies (Eichenfield et al., 2014a).

Atopic dermatitis occurs most frequently in childhood (affecting up to 25% of children) but also occurs in adulthood. The lifetime prevalence of AD in adults is approximately 2%–10% (Bieber, 2010), whereas the 1-year prevalence of AD in adults in the United States has been estimated to be approximately 3% (defined as eczema with asthma/hay fever) (Silverberg & Hanifin, 2013). Approximately 20% of adults with AD have moderate-to-severe disease (DaVeiga, 2012). Skin lesions in moderate-to-severe AD are widespread and appear as erythematous papules and plaques with xerosis, edema, scaling, crusting, excoriations, oozing, lichenification, infiltration, and papulation, which can all vary by age (Bieber, 2010 Eichenfield et al., 2014a).

Atopic dermatitis is associated with a significant burden of illness (Simpson et al., 2016a Whiteley, Emir, Seitzman, & Makinson, 2016), including prominent itch, which is a hallmark of the disease, and has a negative impact on patient quality of life (QoL) and quality of sleep (Blome, Radtke, Eissing, & Augustin, 2016 Green, 2010 Kong, Han, Lee, & Son, 2016 Simpson et al., 2016a). Both disease severity and itch affect aspects of sleep quality, such as delaying falling asleep and increased night waking (Kong et al., 2016 Simpson et al., 2016a).

Effective treatment options are needed to address the significant burden of illness of AD in adults (Whiteley et al., 2016). Currently available treatment options for moderate-to-severe AD such as topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), systemic treatments, including traditional immunosuppressants, or phototherapy are not recommended for long-term use (Eichenfield et al., 2014a 2014b Garritsen, Brouwer, Limpens, & Spuls, 2014; Katayama et al., 2017; Ring et al., 2012a 2012b Sidbury et al., 2014a 2014b).

Dupilumab is a fully human monoclonal antibody, directed against the interleukin [IL]-4 receptor α (IL-4Rα) subunit, that inhibits signaling of both IL-4 and IL-13, which are key drivers of Type 2/Th2-mediated inflammation (Blakely, Gooderham, & Papp, 2016 Gandhi, Pirozzi, & Graham, 2017 Hamilton et al., 2014). Dupilumab was approved in the United States by the Food and Drug Administration (FDA) on March 28, 2017, for the treatment of adults with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable (Food and Drug Administration, 2017). Dupilumab is also approved by the European Medicines Agency (EMA) for use in adults with moderate-to-severe AD who are candidates for systemic therapy (European Medicines Agency, 2017). In phase 2 and 3 clinical studies, dupilumab has been shown to reduce disease severity in patients with moderate-to-severe AD and to have an acceptable and favorable safety profile (Beck et al., 2014 Blauvelt et al., 2017 Simpson et al., 2016b 2016c ;Thaçi et al., 2016). In addition, dupilumab has been shown to improve patient-reported outcomes (PROs) and patient QoL (Simpson, 2017a Simpson et al., 2016b 2016c).

The objective of the two analyses presented here was to evaluate the efficacy and safety of treatment with subcutaneous (s.c.) dupilumab in adults with moderate-to-severe AD using data from a phase 2a (Beck et al., 2014) and a phase 2b (Thaçi et al., 2016) clinical trial of dupilumab. In the phase 2a trial, patients were randomized 1:1 to s.c. dupilumab 300 mg once weekly (qw) or placebo for 12 weeks. The phase 2b trial included additional dosage groups; patients were randomized 1:1:1:1:1:1 to s.c. dupilumab 300 mg qw, 300 mg every 2 weeks (q2w), 200 mg q2w, 300 mg every 4 weeks (q4w), 100 mg q4w, or placebo for 16 weeks. The dupilumab 300 mg qw and placebo groups were included in the pooled analysis. The rationale for pooling data from the two studies was to increase precision using a single set of numbers. In addition, a subanalysis of the phase 2b trial was conducted in patients who had received either s.c. dupilumab 300 mg q2w or placebo. The subanalysis of the dupilumab 300 mg q2w dose in the phase 2b trial was conducted because this dose was ultimately approved.

Methods

Study design

Both the phase 2a and phase 2b clinical trials of dupilumab were multicenter, randomized, placebo-controlled, and double-blinded. In the phase 2a study (ClinicalTrials.gov Identifier: NCT01548404), patients were enrolled at 23 study sites in the Czech Republic, France, Germany, Hungary, and Poland (Beck et al., 2014). A total of 109 patients were randomized to either s.c. dupilumab 300 mg qw (n = 55) or placebo (n = 54). The study drug was given qw for 12 weeks.

In the phase 2b study (ClinicalTrials.gov Identifier: NCT01859988), patients were enrolled at 91 study sites in Canada, the Czech Republic, Germany, Hungary, Japan, Poland, and the United States (Thaçi et al., 2016). A total of 124 patients were randomized to either s.c. dupilumab 300 mg (n = 63) or placebo (n = 61). The study drug was given qw for 16 weeks. Lower doses of dupilumab were also included in this study (200 mg q2w, 300 mg q2w, 300 mg q4w, and 100 mg q4w), but these were not included in the pooled analysis (to enable data pooling). The 300 mg q2w dose is presented as a separate analysis, as this dose was subsequently approved. A loading dose of dupilumab 600 mg was administered to patients randomized to receive dupilumab 300 mg qw or q2w.

The safety follow-up period for both studies was 16 weeks. Patients were required to use a topical emollient (moisturizer) for ≥7 days before and 7 days after baseline (day -7 to day 8). Rescue medication for AD (including but not limited to TCIs, TCSs, and systemic treatmentoptions for AD) could be given at the investigator's discretion; patients receiving rescue medication were discontinued from study treatment and counted as nonresponders in all analyses.

Patients

Enrolled patients were adults (aged ≥18 years) and had AD for at least 3 years before screening, an Eczema Area and Severity Index (EASI) score at baseline of at least 16, an Investigator's Global Assessment (IGA) score at screening and baseline of at least 3, at least 10% of body surface area affected by AD at screening and baseline, and a history of inadequate response to TCSs or TCIs within three months (phase 2a study) or 6 months (phase 2b study) of enrollment.

Key exclusion criteria included previous treatment with dupilumab, use of topical prescription AD medications within 1 week before baseline or systemic AD medications within 4 weeks before baseline, and acute or chronic infections within 1 week before baseline.

Outcomes

Post hoc efficacy outcomes analyzed through week 12 included the mean percent change from baseline in the EASI score (Hanifin et al., 2001), SCORing Atopic Dermatitis (SCORAD) score (European Task Force on Atopic Dermatitis, 1993), SCORAD Visual Analog Scale (VAS) pruritus and VAS sleep loss scores (Kunz et al., 1997), 5-dimension (5-D) pruritus scale score (Elman, Hynan, Gabriel, & Mayo, 2010), and pruritus Numerical Rating Scale (NRS) score (Phan et al., 2012 Yosipovitch et al., 2017) and the proportion of patients achieving IGA scores of 0/1 and 50%, 75%, or 90% improvement (reduction) in EASI score (EASI-50, EASI-75, and EASI-90, respectively).

Safety outcomes included both the number and severity of treatment-emergent adverse events (TEAEs). Treatment-emergent adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA), and TEAE severity was determined by the investigator.

Statistical analyses

For the pooled analysis, efficacy and safety data through week 12 were pooled from the dupilumab 300 mg qw and placebo groups in both clinical trials. The phase 2b subanalysis included efficacy data through week 12 and safety data through week 16 for the dupilumab 300 mg q2w and placebo groups, using data from the phase 2b clinical trial only. For EASI, SCORAD, peak pruritus NRS, SCORAD VAS pruritus, 5-D pruritus, and SCORAD VAS sleep loss scores, data are reported as least squares mean percent change (±standard error); for other efficacy end points, data are reported as the proportion of patients.

The range, recall period, and assessment frequency of these clinician-reported outcomes and PROs are summarized in Table 1. Analysis of covariance was used (with treatment and baseline as covariates) to compare percent changes; a χ2 test was used for proportions. Safety was summarized using descriptive data. All statistical tests were two sided, and p ≤ .05 was considered statistically significant. Missing data, data recorded after dropout, and data recorded after rescue treatment were accounted for with the last observation carried forward method for continuous end points. The proportions of patients with EASI-50/75/90 or SCORAD-50/75/90 included all recorded values with censoring after rescue drug use. Analyses included all randomized patients who received at least 1 dose of the study drug.

Results

Patients

A total of 233 patients were included in the pooled analysis (placebo: n = 115; dupilumab 300 mg qw: n = 118): 109 (placebo: n = 54; dupilumab 300 mg qw: n = 55) in the phase 2a study and 124 (placebo: n = 61; dupilumab 300 mg qw: n = 63) in the phase 2b study. The phase 2b subanalysis included a total of 125 patients (placebo: n = 61; dupilumab 300 mg q2w: n = 64). Baseline demographic and disease characteristics were balanced between the groups (Table 2). In the pooled analysis, the median age at baseline was 33 and 37 years in the dupilumab300 mg qw and placebo groups, respectively; the median duration of AD was 28 years for both groups. In the phase 2b subanalysis, median ages at baseline were 40 and 36 years, and the median duration of AD was 30 and 31 years, in the dupilumab 300 mg q2w and placebo groups, respectively. Most patients enrolled in both studies had AD for most of their lives.

 

 

Efficacy

Disease severity

Dupilumab treatment resulted in a significant improvement (reduction) of disease severity in both the pooled analysis and the phase 2b subanalysis, with significantly greater improvements in the EASI (Figure 1) and SCORAD (Figure 2) scores observed from week 1 to 12 in patients treated with dupilumab compared with placebo in both analyses (p < .0001 vs. placebo for all comparisons).

A significantly higher proportion of patients treated with dupilumab achieved an IGA score of 0/1 at week 12 in both the pooled analysis (dupilumab 300 mg qw: 36.4%, placebo: 4.7%; p < .0001 vs. placebo) and in the phase 2b subanalysis (dupilumab 300 mg q2w: 25.0%, placebo: 0%; p < .0001 vs. placebo) (Table 3). Similarly, a higher proportion of patients treated with dupilumabachieved EASI-50, EASI-75, and EASI-90 responses at week 12 in both the pooled analysis(dupilumab 300 mg qw 83.9% vs. placebo 28.7%, 59.3% vs. 13.9%, and 34.7% vs. 6.1%, respectively; all p < .0001 vs. placebo) and the phase 2b subanalysis (dupilumab 300 mg q2w 81.3% vs. placebo 29.5%, 54.7% vs. 13.1%, and 29.7% vs. 3.3%, respectively; all p < .0001 vs. placebo) (Table 3).

 

 

Pain/discomfort

A higher proportion of patients treated with dupilumab 300 mg qw or 300 mg q2w showed decreased pain/discomfort at week 16 in comparison with placebo (Table 4).

 

Pruritus

In both the pooled analysis and the phase 2b subanalysis, dupilumab treatment resulted in a rapid and significant improvement (reduction) in pruritus, as measured by several PROs (Figures 3–5). At week 1, significantly greater reductions in peak pruritus NRS and SCORAD VAS pruritus scores were observed for dupilumab 300 mg qw versus placebo in the pooled analysis. Peak pruritus NRS scores were reduced by −14.7% (±2.11%) versus 2.5% (±2.15%) (p < .0001 vs. placebo) (Figure 3) and SCORAD VAS pruritus scores by −22.5% (±6.19%) versus 8.8% (±6.24%) (p < .001 vs. placebo) (Figure 4), respectively. Similar results were observed in the phase 2b subanalysis. Peak pruritus NRS scores were reduced at week 1 in the dupilumab 300 mg q2w group versus placebo by −10.0% (±3.17%) versus 3.9% (±3.33%) (p < .01 vs. placebo) (Figure 3) and SCORAD VAS pruritus scores by −13.9% (±5.20%) versus −1.9% (±5.32%) (p < .05 vs. placebo) (Figure 4), respectively.

 

 

 

 

In both analyses, treatment with dupilumab significantly reduced 5-D pruritus scores versus placebo at week 2, which was the earliest postbaseline time point (Figure 5). In the pooled analysis, 5-D pruritus scores were reduced in the dupilumab 300 mg qw group by −25.0% (±1.53%) and in the placebo group by −7.3% (±1.56%) (p < .0001 vs. placebo). Similarly, 5-D pruritus scores were reduced in the dupilumab 300 mg q2w group by −17.8% (±2.36%) and in the placebo group by −6.6% (±2.47%) in the phase 2b subanalysis (p < .001 vs. placebo).

Pruritus continued to improve further through week 12 with dupilumab treatment compared with placebo, as measured by all three pruritus PROs in both analyses. At week 12, in the pooled analysis, peak pruritus NRS scores were reduced in the dupilumab 300 mg qw group versus placebo by −52.8% (±3.00%) versus −8.0% (±3.12%), the SCORAD VAS pruritus scores by −71.0% (±3.9%) versus −19.9% (±4.6%), and 5-D pruritus scores by −41.7% (±1.90%) versus −9.8% (±1.92%), respectively (all p < .0001 vs. placebo). Similar results were observed for the dupilumab 300 mg q2w group vs placebo in the phase 2b subanalysis. At week 12, peak pruritus NRS scores were reduced by −36.7% (±4.38%) versus 5.9% (±4.59%), SCORAD VAS pruritus scores by −50.0% (±5.97%) versus −10.2% (±6.12%), and 5-D pruritus scores by −31.9% (±2.94%) versus −8.0% (±3.06%), respectively (all p ≤ .0001 vs. placebo).

Sleep loss

In addition to its positive effect on itch, treatment with dupilumab in both the pooled analysis and subanalysis resulted in an early and significant improvement (reduction) in sleep loss (Figure 6). The SCORAD VAS sleep loss score was significantly reduced in the dupilumab 300 mg qw group versus placebo in the pooled analysis as early as week 2: the mean percent change was −28.8% (±11.01%) for dupilumab 300 mg qw versus 7.0% (±10.91%) for placebo (p < .05 vs. placebo). Results were numerically similar in the phase 2b subanalysis (−27.8% [±10.59%] for dupilumab 300 mg q2w vs. −4.7% [±11.33%] for placebo, p > .05 vs. placebo).

Sleep loss continued to improve further through week 12 with dupilumab treatment in both analyses. At week 12, the mean percent change in the SCORAD VAS sleep loss score was −75.4% (±5.13%) for dupilumab 300 mg qw versus −19.7% (±6.17%) for placebo in the pooled analysis (p = .0001 vs. placebo) and −51.9% (±10.79%) for dupilumab 300 mg q2w versus −3.8% (±11.55%) for placebo in the phase 2b subanalysis (p = .0001 vs. placebo).

 

Safety

Incidence of TEAEs was similar in both treatment groups in both analyses (Table 5). In the pooled analysis, 96 patients (81.4%) in the dupilumab 300 mg qw group and 93 patients (80.9%) in the placebo group had at least 1 TEAE. In the phase 2b subanalysis, 50 patients (78.1%) in the dupilumab 300 mg q2w group and 49 patients (80.3%) in the placebo group had at least 1 TEAE. Most TEAEs were of mild or moderate severity. In the pooled analysis, the three most common TEAEs (by MedDRA Preferred Term) in the dupilumab 300 mg qw and placebo groups were nasopharyngitis (32.2% and 22.6%, respectively), headache (14.4% and 7.8%, respectively), and conjunctivitis (9.3% and 1.7%, respectively). In the phase 2b subanalysis, the three most common TEAEs in the dupilumab 300 mg q2w and placebo groups were nasopharyngitis (25.0% and 26.2%, respectively), exacerbations of AD (21.9% and 18.0%, respectively), and upper respiratory tract infection (9.4% and 18.0%, respectively).

Serious TEAEs were observed in the pooled analysis in 1.7% and 7.8% of patients in the dupilumab 300 mg qw and placebo groups, respectively, and in the phase 2b subanalysis in 3.1% and 6.6% of patients, respectively. In the pooled analysis, the two most common serious TEAEs observed in the dupilumab 300 mg qw group were viral infection and facial bone fracture (both 0.8% of patients), and the most common serious TEAE in the placebo group was AD exacerbation (4.3% of patients). In the phase 2b subanalysis, the most common serious TEAEs in the dupilumab 300 mg q2w group were exacerbations of AD (1.6%) and syncope (1.6%); in the placebo group, they were AD exacerbation (1.6%), hip dysplasia (1.6%), osteonecrosis (1.6%), and induced abortion (1.6%).

In the pooled analysis, fewer patients receiving dupilumab 300 mg qw compared with placebo discontinued from the study (1.7% vs. 8.7%). In the phase 2b subanalysis, 6.3% and 4.9% of patients in the dupilumab 300 mg q2w and placebo groups, respectively, discontinued from the study. No deaths occurred during either study. Further details on safety have been previously published (Beck et al., 2014 Thaçi et al., 2016).

Discussion

In adults with moderate-to-severe AD, s.c. dupilumab 300 mg administered qw in the pooled analysis of the phase 2a and 2b studies and administered q2w in the subanalysis of the phase 2b study significantly improved disease severity, itch, and sleep loss at week 12 compared with placebo. Dupilumab treatment resulted in significant improvement in itch relative to placebo as early as week 1 and in sleep loss as early as week 2. Dupilumab was shown to have an acceptable safety profile in both studies. The efficacy and safety results reported here are consistent with those of the individual phase 2a (Beck et al., 2014) and phase 2b (Thaçi et al., 2016) studies. In the phase 2a study, dupilumab 300 mg qw significantly improved EASI (p < .001) and peak pruritus NRS (p < .05) scores and significantly improved the proportion of EASI-50 responders (p < .001) versus placebo (Beck et al., 2014). In the phase 2b study, dupilumab qw and q2w significantly improved EASI and SCORAD (both p < .0001) and peak pruritus NRS (p < .0001) scores versus placebo at week 16 (Thaçi et al., 2016). Similarly, the improvements in sleep loss and pruritus are consistent in both analyses with those reported in the phase 2b trial (Simpson et al., 2016b).

The efficacy and safety results reported here are also similar to those of three phase 3 studies in patients with moderate-to-severe AD (Blauvelt et al., 2017 Simpson et al., 2016c). In two phase 3 studies comparing dupilumab with placebo, dupilumab qw and q2w significantly improved EASI and SCORAD (both p < .001) and peak pruritus NRS (p < .001) scores and significantly improved the proportion of EASI-75 responders versus placebo at week 16 (p < .001 vs. placebo) (Simpson et al., 2016c). Furthermore, the combined efficacy of dupilumab demonstrated in these analyses of adults with moderate-to-severe AD validates the role of the Type 2/Th2 cytokines IL-4 and IL-13 in the pathogenesis of AD (D'Erme et al., 2017 Gandhi et al., 2017) and the importance of their inhibition for the treatment of AD (D'Erme et al., 2017 Gandhi et al., 2017 Hamilton et al., 2014).

Current recommended treatment options for adults with moderate-to-severe AD include TCSs, TCIs, cyclosporine A, and systemic corticosteroids (Eichenfield et al., 2014b Ring et al., 2012a 2012b). However, all these treatment options are only indicated for short-term or intermittent use, to limit the occurrence of side effects, or because of a lack of long-term safety data (Eichenfield et al., 2014b ;Frankel & Qureshi, 2012 Kawakami & Soma, 2011 Nicol, 2011 Ring et al., 2012a 2012b). The continuous use of TCSs for long periods should be avoided to limit the occurrence of side effects, e.g., skin atrophy (Eichenfield et al., 2014b). Topical calcineurin inhibitors are associated with a theoretical risk of increased malignancy, and their long-term safety remains to be established (Frankel & Qureshi, 2012). In addition, topical treatment options have limited efficacy over time, especially in patients with widespread and/or severe AD (Eichenfield et al., 2014b Ring et al., 2012b).

Dupilumab has recently been approved for use in adult patients (October 2017), so experience of dupilumab in the primary care practice setting is limited. In line with the FDA and EMA product labeling (European Medicines Agency, 2017 Food and Drug Administration, 2017), the International Eczema Council recommends the use of systemic therapies such as dupilumab if intensive topical therapy has been unsuccessful in adults with moderate-to-severe AD (Simpson et al., 2017b). The analysis reported herein excluded patients who used topical prescription medications within 1 week; however, in the clinical practice setting, these patients may continue to use topical prescriptions when initiating dupilumab (Food and Drug Administration, 2017). Dupilumab has demonstrated efficacy in reducing disease severity in adults with moderate-to-severe AD along with an acceptable safety profile (Beck et al., 2014 Blauvelt et al., 2017 Simpson et al., 2016b 2016c Thaçi et al., 2016); as the product label does not require immunosuppression, close monitoring, laboratory testing, or treatment adjustments (Food and Drug Administration, 2017), dupilumab is suitable for use by primary care physicians for the management of these patients. A health care provider (i.e., nurse) should provide guidance with the administration of s.c. dupilumab q2w, which can be self-injected by the patient and/or caregivers once training is provided (Food and Drug Administration, 2017). Patients treated with dupilumab should avoid live vaccines. In a clinical study of patients with AD, dupilumab did not indicate clinically relevant effects on CYP450 enzymes, including CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity (European Medicines Agency, 2017; data on file).

This report has several limitations. These include a short time duration to assess efficacy, safety, and QoL, and a homogeneous study population in terms of race. To enable pooling of data from two phase 2 studies that had different double-blind treatment durations, data from the phase 2b study were truncated at 12 weeks. Safety data are limited to week 12 in the pooled analysis and to week 16 in the phase 2b subanalysis and do not include posttreatment adverse events.

Conclusions

In adults with moderate-to-severe AD, this pooled analysis of two phase 2 studies demonstrated that s.c. dupilumab 300 mg qw significantly improved AD severity, itch, and sleep loss at week 12 compared with placebo. A subanalysis of the phase 2b study confirmed that dupilumab 300 mg q2w also significantly improved these same symptoms at week 12. Improvement in itch relative to placebo occurred as early as week 1 and improvement in sleep loss occurred as early as week 2. In both analyses, dupilumab had an acceptable and favorable safety profile. Dupilumab is the first biologic agent to be approved for the treatment of adults with moderate-to-severe AD and is a promising therapy option.


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