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Follow the 2022 AAD Conference to focus on AD frontiers
On March 25, 2022, the annual American Society of Dermatology (AAD) Annual Meeting was held. The conference brings together dermatologists from all over the world, bringing us a variety of exciting content in the field of dermatology diagnosis and treatment in the form of research reports, case sharing and interactive discussions.
Atopic dermatitis (AD) has always attracted much attention at international dermatological conferences. With the development of the biomedical field in recent years, AD therapy has ushered in a new era of biological therapy, and the clinical treatment model has undergone a historic change. In this AAD conference, many researchers have discussed and discussed this, let's follow the small editor to understand the relevant content!
Traditional treatment is stretched thin,
AD enters a new era of biological therapy
AD therapy includes basic therapy (e.g., moisturizers, emollients), topical pharmacotherapy, phototherapy, and systemic therapy: patients with mild AD often take topical calcineurin inhibitors, glucocorticoids, and other drugs, while patients with moderate to severe AD should consider using systemic therapy, such as glucocorticoids, systemic immunosuppressants. However, many real-world studies have found that the above topical and systemic treatment methods have certain limitations in terms of effectiveness and safety, and the emergence and application of the biological agent - IL-4/IL-13 inhibitor dupridomab has changed the pattern of AD treatment.
At this AAD conference, researchers presented a study for children with moderate to severe childhood AD ([1]. The results of the study show that at present, topical therapy is still the most commonly used treatment method for children with AD (baseline accounting for about 77%), and the common systemic treatment drugs are systemic glucocorticoids and traditional immunosuppressants (eg, methotrexate, cyclosporine).
Based on baseline assessments of eczema area and severity index (EASI), lesion affected area (BSA), and patient-reported outcomes (PROs), pediatric AD patients had poor disease control based on topical treatment, while the Peak Pruritus Numerical Rating Scale (PP-NRS) score showed that conventional systemic therapy did not help patients manage symptoms such as pruritus well, and only patients in the MTX treatment group had a significant improvement in quality of life score (CDLQI). Accordingly, the treatment needs of children with AD are not fully met, whether it is topical treatment or conventional systemic treatment.
What about adult AD patients? A prospective observational study from Europe (eurostaD study) explored systemic treatment patterns in adult patients with AD (median follow-up time was 20.5 months) [2]. The results of the study showed that 85.4% of adult patients receiving systemic therapy were moderate to severe AD; during the follow-up period, 76.6% of patients experienced treatment discontinuation (mainly due to lack of efficacy, disease has been well controlled, etc.), 20.2% experienced the conversion of systemic therapy (of which 55.2% were poorly treated), and 87.6%, 81.5%, and 66.3% of patients receiving systemic glucocorticoids, cyclosporine, and methotrexate stopped treatment during the follow-up period.
Coincidentally, a five-year international multicenter observational study (GLOBOSTAD) also investigated baseline features and treatment patterns in patients with AD prior to treatment with dupridomab [3]. The study found that 75.7% of patients received dupridosumab treatment due to previous treatment failure, and 55.9% of patients reported receiving other systemic therapy prior to receiving duprizumab. However, the disease burden in these patients remains very high in terms of disease severity at baseline and response to previous treatments (Table 1), and the disease control effect of traditional treatments is not satisfactory.
Table 1: Disease severity at baseline in patients with GLOBOSTAD
From the above studies, it can be seen that there are shortcomings in the traditional treatment of AD. Is the application of the new biologic dupridomab expected to change this?
In the PEDISTAD study, 2.6 percent of pediatric AD patients received dupridomab, and although these children had a higher severity of disease at baseline, several clinical evaluations and PROs improved significantly compared with immunosuppressants such as cyclosporine and methotrexate (Figure 1) [1], while in the EUROSTAD study, 38.6 percent of adult AD patients received dupridosumab, of which only 18.4 percent were treated with dupridosumab. Patients who discontinue treatment during follow-up are more likely to continue treatment than methotrexate and cyclosporine (figure 2) [2]. Therefore, when the traditional treatment model encounters a bottleneck, the emergence and application of dupridosumab brings new hopes for the long-term control of AD patients.
Figure 1: Improvement of clinical evaluation indicators and PROs in children with AD after receiving different systemic treatment drugs in the PEDISTAD study
Figure 2: Treatment time analysis of different systemic treatment regimens in the EUROSTAD study
Long-term treatment brings multiple clinical benefits, and dupridomab drives a shift in traditional treatment models
AD is a chronic disease, and the recurrence and variety of diseases determine the long-term and arduous nature of treatment management. So, what benefits can dupridosumab bring to the long-term treatment of AD, and what changes have occurred to the AD treatment model?
At the conference, researchers presented data from the PROSE Registry, and clinical evaluation indicators and PROs, including EASI, BSA, PP-NRS, patient eczema self-examination scoring scale (POEM), DLQI, and patient overall disease assessment (PGAD), continued to improve significantly after enrolling patients with AD (≥12 years of age) on 18 months of prifolizumab (Figure 3) [4].
Figure 3: Improvement of clinical evaluation indicators and PRO in patients with AD 18 months after receiving dupridomab
In addition, a review of the study data from the real-world study (RELIEVE-AD study) found that in the longer (30-36 months) treatment follow-up, dupridomab still maintained good efficacy, the proportion of patients without disease recurrence increased significantly with the passage of treatment time (Figure 4), the patient's sleep status also improved rapidly and continuously, the AD-related skin pain, burning and sensitivity scores decreased significantly, and the itching symptoms were significantly alleviated (Figure 5) [ 5]。 These studies have confirmed the effectiveness of dupridomab in the long-term control of AD.
Figure 4: Proportion of patients without episodes of AD in the past 4 weeks
Figure 5: Improvement in sleep and associated symptoms in patients with AD
In addition, patients with AD are susceptible to skin infections that worsen skin lesions due to skin barrier disorders. The results of a retrospective, observational study using data from the U.S. Optum Clinformatics database showed a significant reduction in the incidence of skin infections in patients with AD during the 12 months of treatment with duprizumab, from 24.7% at baseline to 11.2%, and a significant reduction in the use of systemic/topical antimicrobials (Figure 6) [6], indicating that duprizumab helped reduce the risk of skin infections during treatment and was relatively safe.
Figure 6: Proportion of patients with AD who (A) have skin infections and (B) who use all-cause antimicrobials before and after the use of dupridosumab
Combinations are a common mode of use in traditional AD treatments, but if used improperly, they can cause inappropriate drug interactions, reduce expected efficacy, or produce unexpected adverse reactions. American scholars have analyzed and discussed the combination of adult AD patients in the RELIEVE-AD study after receiving dupridosumab, and the results were published at this AAD conference [7]. The report showed a significant decrease in combinations of patients with AD after receiving dupridomab therapy, with the proportion of patients treated with monotherapy (without concomitant medication) rising from 12.8% at baseline to 39.6% at 1 month of treatment, and this proportion continued to rise during follow-up, with more than half (54.4%) of patients reporting only dupridosumab therapy at 30 to 36 months (Figure 7).
Figure 7: Number of combinations of other treatment classes (left) and concomitant therapies by treatment class (right) during treatment with dupridosumab
(Treatment categories total 5 categories: topical drugs, Crisaborole ointment, systemic steroids, systemic immunosuppressants, ultraviolet therapy, excluding dupridosumab)
The application of dupridomab in the clinical treatment of AD not only improves the effectiveness and safety of treatment, but also helps to reduce the risk of infection and the complexity of medication. This new treatment option has revolutionized our AD treatment model.
Targeting the core mechanism of type 2 inflammation,
Expand the field of disease treatment
Th2 cell-mediated type 2 inflammation is considered to be a basic feature of AD, and type 2 inflammatory cytokines IL-4 and IL-13 are important cytokines that mediate the onset of AD. Dupridomab inhibits type 2 inflammation by targeting both IL-4 and IL-13, doubly blocking their mediated signal transduction pathways, and thus exerting efficacy.
In addition to AD, type 2 inflammation drives the pathophysiology of a variety of other diseases. Based on the GLOBOSTAD study data, the researchers found that the vast majority (81.3%) of AD patients also had other type 2 inflammatory comorbidities, such as allergic rhinitis and asthma [8]. Dupridomab, which is effective against type 2 inflammation, may also have potential efficacy in the treatment of AD comorbidities. At this AAD conference, *there were also reports of the use of dupridomab in the treatment of other type 2 inflammatory diseases.
LIBERTY-PN PRIME2 is a randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical trial evaluating the efficacy and safety of dupridoruzumab in adult patients with severe prurigo nodosuma (PN) with severe pruritus symptoms in 20 nodules ≥ [9]. The PRIME2 study showed that dupridomab had a significant role in improving pruritus and skin lesions in adult patients with PN compared with placebo (Figure 8); and the safety of dupridomab in the treatment of PN was consistent with known data (Table 2).
Figure 8: Wi-NRS improves ≥4 (left) and IGA PN-S is 0 or 1 (right) proportions
WI-NRS improvement ≥4: patient pruritus was clinically significantly reduced compared to baseline;
IGA PN-S: Investigator Overall Score
Table 2: Percentage of patients with adverse events (TEAE) during treatment from baseline to week 24≥1 cases
In addition, the results of a clinical trial exploring the potential efficacy of dupridomab in chronic spontaneous urticaria (CSU) were published [10]. Clinical treatment of CSU is mainly based on antihistamines, but on this basis, there are still many patients whose diseases are not effectively controlled, and persistent itching and rash. LIBERTY-CSU is a randomized, double-blind, placebo-controlled Phase 3 clinical trial in which study A enrolls patients aged ≥6 years of moderate to severe CSU who are symptomatic despite H1 antihistamines and have not previously been treated with omalizumab. Patients with CSU who received dopridomab had a significant improvement over baseline at 24 weeks on the Pruriyumab score (ISS7), urticaria activity score (UAS7), and urticaria severity score (HSS7) at 24 weeks (Figure 9), and dupridomab was well tolerated and safe in patients with CSU. This finding brings a new light to patients with CSU who cannot rely solely on antihistamines for disease control.
Figure 9: At 24 weeks of dupridomab treatment, patients with CSU had significant improvements in ISS7, UAS7, and HSS7 compared to baseline
*Dupridomab is currently approved in China only for medium to severe AD indications in children 6 years of age and older and adults with poor control of topical medications or are not recommended for topical use
summary:
This AAD conference is full of highlights. Research results in various skin disease fields continue to emerge, which has effectively promoted the development of the discipline. Many of these research reports focus on AD treatment, and conduct in-depth analysis and discussion on the pattern changes brought about by the traditional treatment mode of AD and biological therapy. Dupridomab is a novel biologic for the treatment of AD that has been shown in the real world to sustainably improve patients' symptoms and signs as well as quality of life, with good overall safety and support for long-term control of AD. Treatment of dupridomab also reduces concomitant medications and the risk of skin infections, and has potential benefits for the treatment of AD comorbidities, bringing multiple benefits to patients and innovative treatment models.
bibliography:
[1] Eulalia Baselga, et al. AAD 2022. #P33553.
[2] Marjolein de Bruin-Weller, et al. AAD 2022. #P34574.
[3] Silvia M. Ferrucci, et al. AAD 2022. #P34332.
[4] Jerry Bagel, et al. AAD 2022. #P34313.
[5] Bruce Strober, et al. AAD 2022. #P33322.
[6] Peck Ong, et al. AAD 2022. #P34326.
[7] Dimittri Delevry, et al. AAD 2022. #32929.
[8] Piergiacomo Calzavara-Pinton, et al. AAD 2022. #P34329.
[9] Gil Yosipovitch, et al. Presented at the 2022 AAD；Boston, MA, USA; March 25-29, 2022.
[10] Marcus Maurer, et al. AAD 2022. #P33004.
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