Doc. Miloslav Salavec: We Still Encounter Delayed Initiation of Biological Treatment in AD and Many Other Diagnoses
Not all patients with atopic dermatitis (AD) who are indicated for biological treatment with dupilumab manage to reach centers where the treatment is provided. It's even more unfortunate when there's ample evidence that the effects of this therapy on disease manifestations and overall quality of life extend beyond just the patients. It also impacts the lives of their close ones who care for those with atopic dermatitis. Head of the Clinic of Venereal and Skin Diseases at Charles University and the University Hospital Hradec Králové Doc. MUDr. Miloslav Salavec, CSc., evaluates how dupilumab has performed over several years of real clinical practice and the specific benefits it has brought to patients.
It has been several years since biological treatment became available for moderate to severe atopic dermatitis. How has the quality of life for patients with this diagnosis changed from your perspective?
After the implementation of biological therapy—in this case, monoclonal antibody dupilumab—the quality of life changed significantly not only for the patients who started using it but also for their family members and close individuals. The quality of life in severe atopic dermatitis was always significantly affected. The optimal therapeutic goal is to achieve healed or nearly healed skin (MDA) defined by IGA 0/1 or obtaining BSA 90%, respectively BSA up to a maximum of 2% of skin surface or achieving EASI 90 with minimal impact of the disease on quality of life.
What benefits of biological treatment do you consider most crucial for your atopic patients?
It mainly relates to the excellent impact on the type 2 inflammatory process, manifesting in the reduction of pruritus and improvement in sleep quality, which consequently leads to an overall impact on the quality of life for atopic patients. It should also be noted that dupilumab normalizes the function of the skin barrier, thus contributing to the reversal of epidermal pathology of AD.
How has the application of dupilumab affected the effectiveness indicators of the treatment, especially the severity of atopic dermatitis and associated itching?
Significant itch reduction, improvement in sleep quality, and overall quality of life related to dupilumab have been demonstrated by numerous clinical studies and real-world data. For instance, according to the CHRONOS clinical study, in the 52nd week of therapy, the participants achieved EASI 50 in 78.7% of cases, EASI 75 in 65.2%, and EASI 90 in 50.9% of cases. Thus, nearly 51% of patients achieved improvement defined based on EASI 90 score. A similar reduction was found according to another scoring system, SCORAD. Post hoc analyses confirmed significant reductions in pruritus, pain, and sleep disruption compared to placebo.
Can you say which patients have benefited most from this therapy? And for whom would you not recommend it (and why) even though they fall into its indication?
Its effect on the inflammatory process has been confirmed, especially in severe forms of AD. Besides the mentioned quality of life in all its domains, it positively affects the occurrence of anxiety and depression. Long-term administration of dupilumab leads to an improvement in symptoms, and quality-of-life parameters remain consistent and permanent. Caution in its administration is advisable in patients with chronic or recurrent inflammatory eye conditions (conjunctivitis, blepharitis).
How does dupilumab work in patients with multiple diagnoses based on type 2 inflammation?
It has undoubtedly shown its effect in other types of diseases caused by type 2 inflammation. It is approved for the treatment of chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis, as well as for the skin disease prurigo nodularis, where both clinical and statistically significant improvements in pruritus and skin lesions have been demonstrated.
How does dupilumab stand in terms of ease of administration?
For adult patients with AD, the recommended initial dose is 600 mg, followed by a dose of 300 mg every other week.
For adolescents aged 12 to 17 years weighing up to 60 kg, the recommended dose is 400 mg, followed by 200 mg doses at the same interval as adults. For adolescents weighing 60 kg or more, the recommended initial and subsequent dose and administration intervals are the same as adults.
For children aged 6 to 11 years weighing up to 60 kg, the recommended initial dose is 300 mg, with another 300 mg after 2 weeks, and subsequently at 4-week intervals (starting 4 weeks after the second dose). Based on a physician's assessment, the dose can be increased to 200 mg every two weeks. For patients weighing 60 kg or more, the recommended initial and subsequent doses and intervals are the same as for adults.
For smaller children aged 6 months to 5 years weighing up to 15 kg (but at least 5 kg), the recommended initial dose is 200 mg, followed by 200 mg every 4 weeks. For children weighing between 15 and 30 kg, the initial dose is 300 mg, followed by 300 mg every 4 weeks.
Dupilumab can be used alongside topical corticosteroids or without them. However, if no therapeutic response is observed after 16 weeks of treatment, discontinuation should be considered.
How soon can the definitive onset of dupilumab effect generally be observed?
Improvement defined by EASI 75 score can be observed in nearly 70% of patients within 4 months of starting therapy. A significant decline in the subcomponents of the SCORAD system (oozing, crust formation, lichenification, skin dryness, erythema, etc.) was recorded by the 52nd week of treatment.
How about long-term administration of this substance and monitoring patients on the treatment?
Dupilumab can be administered long-term, with patients monitored focusing on skin inflammatory changes and factors impacting their quality of life. Monitoring should also consider eye conditions and the potential occurrence of viral infections (mainly those caused by herpes simplex and varicella zoster viruses).
Do all the effects of dupilumab mentioned also apply to children and adolescents?
Yes, the conclusions regarding its effectiveness and benefits in improving the quality of life for patients with AD can also be extended to children and adolescents.
Your colleague, MUDr. Michaela Nováková from the Dermatovenerology Clinic at the Second Faculty of Medicine of Charles University and the University Hospital Bulovka, mentioned in an interview with us that patients with moderate to severe atopic dermatitis often experience delayed referral to centers for the initiation of biological treatment. Her hypothesis or explanation for this is that the alternating flares and remissions might “lull” outpatient dermatologists and reinforce the belief that biological treatment is not yet necessary. Can you confirm this, or do you have a different experience?
We have a similar experience at our clinic. Of course, part of the issue can be attributed to the chronicity of the disease with its typical alternating acute flares and remissions. However, it's not certain whether this is the only factor. Economic factors and possibly limited awareness of the effective therapeutic interventions available for this clinical entity may also play a role. We encounter delayed initiation of biological therapy in many other diagnoses for which it is currently indicated.
Kristýna Poulová
editorial team proLékaře.cz
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