Treatment of eczema with Elidel® could reduce asthma risk by halting "atopic march"

Main Category: Respiratory / Asthma
Article Date: 21 Nov 2004 - 0:00 PDT

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A groundbreaking study now under way will establish whether effective treatment of atopic eczema in infancy could modify the course of atopic eczema and reduce the risk of developing asthma later in childhood. The ongoing study, details of which were presented today at the congress of the European Academy of Dermatology and Venereology in Italy, is at the forefront of new research to investigate potential benefits of long-term treatment using Elidel® (pimecrolimus) cream 1%.

It is estimated that up to 80% of children who suffer from the chronic skin condition atopic eczema subsequently go on to develop other related diseases such as allergic asthma and rhinitis (or 'hay fever')1 - a sequence known as the "atopic march". This widely-recognized disease progression is being investigated in a clinical trial called SAM (Study of the Atopic March), involving 1,100 infants aged 3-18 months who are currently being recruited at 20 centers in the US.

For the first 36 months of treatment in this study, investigators will assess the effect of long-term treatment with Elidel on the natural course of atopic eczema. Following this randomized, double-blind phase of the study, eligible participants will receive the non-steroid cream for a further 33 months on an open-label basis. On completion of the study, efficacy will be assessed in terms of the diagnosis and time of onset of asthma. Other signs of allergic sensitivity such as food allergies, allergic rhinitis, allergic conjunctivitis, and levels of the immune antibody IgE will also be evaluated.

The SAM study explores the hypothesis that Elidel-based long-term management of atopic eczema, starting in infants at the first manifestation of the disease, provides control of eczema, maintains integrity of the skin barrier function, and reduces penetration of allergens through the upper layers of the epidermis. This intervention is expected to normalize the exposure of immune-competent cells in the deeper layers of the epidermis, reducing their ability to mount an atopic immune response that could affect the development of atopic inflammation in other organs, such as asthma in the lungs (the so-called "atopic march").

Prof. Johannes Ring of the Department of Dermatology and Allergy, Biederstein, Technical University Munich, Germany, who presented details of the study design at EADV, said: "The aim is to determine whether use of topical calcineurin inhibitors at the first diagnosis of eczema reduces the incidence of asthma by the age of six. We know that atopic eczema is often the earliest manifestation of the atopic disposition, and it is important to investigate whether this type of early intervention may provide benefits not just by controlling atopic eczema through flare prevention, but also by offering the potential for disease modification - in effect, halting the atopic march in its tracks."

Elidel and the quest for long-term control

The Study of the Atopic March builds on growing evidence from clinical trials and clinical experience that treatment with Elidel can help to control eczema and reduce the painful and distressing cycle of flare-ups that characterize the disease.

The need for long-term treatment strategies to control eczema is highlighted by the findings of ISOLATE, the International Study Of Life with ATopic Eczema,2 involving 2,000 patients and caregivers in eight countries. The results, revealed for the first time today at EADV, show that 75% of respondents believed that being able to control their eczema effectively would be the single most important improvement to their quality of life. In addition, 67% of patients and caregivers said that their preferred treatment option was to apply a non-steroid medication as early as possible to prevent flare-ups.

Evidence from clinical trials indicates that when applied at the first signs and symptoms of atopic eczema, Elidel prevents the progression to a full-blown flare-up and prolongs flare-free time, allowing topical corticosteroids to be reserved for use as rescue therapy in severe 'breakthrough' flare-ups.

Another aspect of long-term treatment is being explored through an innovative clinical trial which aims to shed more light on a paradoxical aspect of the flare cycle - namely that even after a flare-up has subsided and the skin appears normal, underlying inflammation is still present in patients with atopic eczema. The multi-center, double-blind study called PARADIGM will identify cellular and molecular changes in the post-lesional phase of eczema and assess the effect of Elidel. Skin biopsies will be taken from cleared or 'normal' skin of 70 adult patients with mild or moderate atopic eczema, previously treated with either Elidel or a control, and compared with skin from non-atopic volunteers.

Prof. Giampiero Girolomoni of the Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy, said: "It is clear that pre-emptive, long-term steroid-sparing strategies for the management of atopic eczema are long overdue. Given the opportunity, patients would welcome a new treatment approach in which their eczema - and in particular, their flares-ups - are controlled and occur at more extended intervals. Historically, physicians have relied on short-term 'reactive' therapy involving topical steroids, but patients deserve a more proactive strategy that enables them to apply topical non-steroid treatment at the very first signs or symptoms of an eczema flare-up and control their disease in the longer-term."

About Elidel

Elidel (pimecrolimus) cream 1% is licensed for the short-term and intermittent long-term treatment of mild to moderate atopic dermatitis (AD), to prevent the progression of flares in both children and adults. Elidel is the only non-steroid treatment for atopic dermatitis that is clinically proven to prevent flare progression and improve disease control, without the side effects associated with conventional treatment using topical steroids.

Elidel may be used on all skin surfaces, including delicate areas such as the face, neck and skin folds, with no limits on duration or volume of use. The active ingredient is pimecrolimus, which is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var. ascomyceticus. Pimecrolimus selectively blocks the production and release of cytokines from T-cells. These cytokines in the skin cause the inflammation, redness and itching associated with eczema.

Elidel, developed and marketed by Novartis, was first launched in 2002 and is now registered in around 90 countries.

This release contains certain forward-looking statements that can be identified by the use of forward-looking terminology, such as "could reduce", "will", "is expected", "aim", or similar expressions, or by express or implied discussions regarding potential additional marketing approvals or future sales of Elidel. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause the actual results with Elidel to be materially different from any future results, performance, or achievements expressed or implied by such statements. There can be no guarantee that Elidel will receive any additional marketing approvals in any other countries, or that it will reach any particular sales levels. Any such results can be affected by, among other things, uncertainties relating to clinical trials, including uncertainties as to the results of the ongoing SAM trial, regulatory actions or delays or government regulation generally, the ability to obtain or maintain patent or other proprietary intellectual property protection, competition in general, government, industry, and general public pricing pressures, as well as factors discussed in the Company's Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 80,000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

References

1 ISOLATE (International Study Of Life with ATopic Eczema). Data on file
2 Eichenfield L et al. Pediatrics 2003;111:608-616

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