The FINANCIAL — Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease that affects many children and adults, often significantly compromising their quality of life.
"Treatment success, therefore, should be considered not only from a clinical point of view but also from the patient’s perspective. An Intendis-sponsored satellite symposium held during the European Academy of Dermatology and Venerology (EADV) Congress in Paris, made clear that treatment success factors that make a difference in the management of AD today often go beyond a proven efficacy and favorable tolerability profile to include the tailoring of convenient treatments to patients’ needs and to enhance compliance." Bayer reports.
Wide formulation range and unique once daily application
“Especially in AD,” Professor Thomas Ruzicka, Munich, Germany, told delegates, “we need to work with our patients to find the solution to the attainment of long-term compliance.” As every patient is different, he explained, the key is to accurately diagnose the type of AD a patient presents and then to match it not only to the right drug but also to the correct formulation of that drug so that the patient receives the benefits they need in an acceptable treatment protocol.(1)
Thus, drugs that effectively treat AD and have excellent safety profiles, such as the modern glucocorticosteroid (GC) MPA (methylprednisolone aceponate, a non-halogenated, diester corticosteroid; Advantan), need to be available in a broad range of formulations that suit all skin types and all levels of AD. Having a wide range of formulations available, including cream, ointment, fatty ointment, milk and solution, also allows tailoring and adjustment of the treatment choice to the patient’s skin condition and location of skin lesions without having to switch active ingredient. MPA, which requires a single, daily application to be effective, also offers just such a broad range of formulations. Together, these features may aid compliance by giving patients a choice of topical agents to make their treatment more acceptable.
Proven efficacy
Once absorbed into damaged and inflamed skin, MPA exhibits a fast onset of action that is accelerated by rapid, local metabolism of MPA into its active metabolite, methylprednisolone 17-propionate (MPP), by the skin’s own enzymes (esterases). Following systemic absorption, MPP is rapidly inactivated and excreted. MPA’s local metabolism is believed to contribute to the prompt relief of the symptoms of AD while its rapid inactivation reduces the potential for systemic side effects.(1)
Treatment benefits: children and adolescents
MPA has been compared with drugs that are also currently used to treat AD. For example, once daily MPA 0.1% ointment and twice daily tacrolimus 0.03% ointment were compared in children and adolescents with acute severe to very severe AD.(2) MPA and tacrolimus were equally effective when assessed using the Investigator’s Global Assessment (IGA). However, when the eczema area and severity index (EASI), intensity of itch and quality of sleep were considered, significant advantages of MPA were observed.
New findings underscore high safety profile
Since GCs were first introduced, newer GCs with improved benefit-to-risk ratios or ‘therapeutic indices’ have been developed, including compounds such as MPA and mometasone furoate (MMF). Like MPA, MMF has a high therapeutic index. Professor Thomas Luger, Münster, Germany, outlined a recent investigation,(3) which indicates that MPA displays higher specificity in nuclear receptor binding compared with MMF. Extrapolating these findings to the clinical situation, the study investigators predict that MPA will be less likely than MMF to induce unwanted side-effects. Support for this prediction comes from an experimental study in animals(3) and a study of healthy volunteers(4) where, after 6 weeks’ occlusive application, atrophy and telangiectasia were significantly less pronounced with MPA than with MMF (p<0.001). Indeed, atrophy and telangiectasia were rated as ‘pronounced or very pronounced’ in most volunteers receiving MMF; side-effects were rated as slight to moderate after 6 weeks treatment in volunteers receiving MPA.
Effective maintenance treatments
The prolongation of the symptom-free periods is the goal of every patient with chronic AD, which often recurs as flares. The results of a recent study demonstrate that MPA cream, once daily, effectively stabilized AD flare in 89% of more severely affected patients.(5) Furthermore, MPA twice weekly plus emollient also proved to be an effective maintenance treatment regimen to control AD.(5)
As Professor Ruzicka told delegates, “The latest generation of GCs allows physicians to really focus on the patient's needs, focusing not only on efficacy and safety, but also on enhancing convenience and compliance. This is an important development in clinical practice that will continue in the future.”
Next generation continues the trend
Indeed, many additional therapeutic agents are being investigated to improve further the future management of this condition, explained Professor Thomas Schwarz, Kiel. Currently, great effort has been targeted into developing new GC receptor ligands.(6) These ligands, called Selective Glucocorticoid Receptor Agonists (SEGRAs), represent a new class of anti-inflammatory compounds. It is anticipated that agents exhibiting such properties would show improved therapeutic indices beyond those of currently available GCs.
References:
(1) Ruzicka T. Int J Clin Practice 2006;60:85-92.
(2) Bieber T et al. Allergy 2007;62:184-9.
(3) Mirshahpanah P et al. Exp Dermatol 2007;16:753-61.
(4) Kecskés A et al. J Am Acad Dermatol 1993;29:576-80.
(5) Peserico A et al. Br J Dermatol 2008;158:801-7.
(6) Schäcke H et al. Mol Cell Endocrinol 2007;275:109-17.
