Miralex Skin Cream

No. S000294
Vancouver Registry

IN THE SUPREME COURT OF BRITISH COLUMBIA

BETWEEN:

STEPHEN ALAN HEAD
PLAINTIFF

AND:

MIRALEX HEALTH CARE INC. AND HUESON PHARMACEUTICAL CORP.
DEFENDANTS

BROUGHT PURSUANT TO THE CLASS PROCEEDINGS ACT R.S.B.C. 1996, c.50

AFFIDAVIT OF DR. STUART MADDIN

I, Dr. Stuart Maddin, physician, of 835 West 10th Avenue, Vancouver, B.C., MAKE OATH AND SAY THAT:

QUALIFICATIONS

I am the Emeritus Clinical Professor of the Division of Dermatology, Faculty of Medicine, at the University of British Columbia. Attached as Exhibit "A" is a copy of my curriculum vitae.

USE OF MIRALEX SKIN CREAM

Although I do not know exactly who used the Miralex Skin Cream, the marketing literature that I have reviewed for the product suggests that it was directed towards persons sufferring from psoriasis. Patients with dry scaling skin conditions such as eczema may also have been attracted to this product.

PSORIASIS

Psoriasis is a common skin disorder that usually presents as a pinkish-red skin lesions covered with silvery white scale. This most common type of psoriasis is called "plaque psoriasis."

The degrees of severity of psoriasis are divided into three categories: mild, moderate and severe.

Psoriasis presents in several different clinical variants along with varying degrees of severity. The difficult and sometimes dangerous variants display blisters (pustular psoriasis), and extensive involvement with severe pruritus and red indurated skin (erythrodermic psoriasis). Other common psoriatic variants exhibit rain-drop like lesions (guttate psoriasis) and flat pinkish-red lesions involving skin folds such as axillae, breasts, inner thighs and gluteal cleft (inverse psoriasis).

CAUSES OF PSORIASIS

No one knows what causes psoriasis, though it is now generally accepted that it reflects both a genetic component as well as immunologic defect. One in three people report a family history of psoriasis, but there is no regular pattern of inheritance. There are cases in which patients with no apparent family history of the disease will develop psoriasis.

The pathophysiologic mechanism of psoriasis has not yet been established, but recent reports suggest that superantigans may play a part by activating T-cells which through a cascade of events produce skin lesions.

Whether a person actually develops psoriasis may depend on something "triggering" its appearance. Some "trigger factors" that can result in a flare-up are systemic infections such as sore throat, minor injury to the skin (the Koebner phenomenon), vaccinations, and medications such as lithium or corticosteroids.

Once something triggers a person's genetic tendency to develop psoriasis, the immune system responds with excessive skin cell reproduction.

THE PSORIASIS CYCLE

The growth of the skin cells are specifically programmed. With normal growth, skin cells are created in the basal cell layer, and then move up through the epidermis to the stratum corneum, the outermost layer of the skin. Dead cells are shed from the skin at about the same rate as new cells are produced, maintaining a balance. This normal process takes about 28 days from cell birth to death.

In the case of psoriasis, skin cells are produced at a much faster rate. Such changes are accompanied by increased blood supply and localized inflammation. These changes result in the production of the typical psoriatic lesion.

When a patient has psoriasis, the cells are pushed to the surface from the underlying basal cell layer in as little as 2-4 days, and the skin cannot shed the cells fast enough. The excessive skin cells build up and form elevated, scaly lesions. The white scale (called "plaque") that usually covers the lesion is composed of dead skin cells, and the redness of the lesion is caused by increased blood supply to the area of rapidly dividing skin cells.

Attached as Exhibit "B" is an excerpt from my text Current Dermatological Therapy discussing psoriasis generally.

LIVING WITH PSORIASIS

The well-known author John Updike has described in graphic detail what it is like to live with psoriasis. Attached as Exhibit "C" is an article quoting Mr. Updike.The pain is more than skin deep. The emotions suffer as well. It presents people with physical limitations and disfiguration. Further, its tedious daily care always demands too much time. Embarrassment, frustration, fear, and depression are common. In extreme cases, a loss of self-esteem results in a complete withdrawal from society. Hence the quest on the part of patients for anything which might ease their suffering.

TREATMENT OPTIONS

It is very common for people with psoriasis to be under the care of a physician. Generally people with psoriasis should be under the care of a physician unless their psoriasis is quite minimal.

There are a number of antipsoriatic therapeutic drugs and physical devices available which, when properly used, provide varying degrees of success depending upon the type and severity of the disease. Generally these treatments must be prescribed and monitored by a physician. The treatment options currently available are outlined below.

Sunshine

Apart from the photodamaging potential, natural sunlight can significantly improve, or clear, psoriasis. Regular daily doses of sunlight taken in short exposures are frequently recommended. This natural approach to treating psoriasis is referred to as climatotherapy.

Tar

Treating psoriasis with crude tar is a very old remedy. Tar preparations are available over-the- counter or as prescription items when combined with other antipsoriatic compounds. The tar often stains and stinks.

Anthralin

Anthralin (Dithrinol) is a topical formulation which has been used to treat psoriasis for many years. It is prescribed in a range of concentrations.

Vitamin D3

Calcipotriol (Dovonex), a synthetic vitamin D3 analog, is used to treat mild to moderate psoriasis. It is a prescription medication with few side effects. Calcipotriol is available in several dosage forms as an odorless, non-staining ointment, cream and scalp solution.

Phototherapy UVB (Broad band) and UVB (Narrow Band)

Medically supervised administration of ultraviolet light B (UVB) is used to control widespread or localized areas of stubborn and unmanageable psoriasis lesions. It is used when topical treatments have failed, or it is used in combination with topical treatments.

Photochemotherapy (PUVA)

PUVA (an acronym for the combination of the drug psoralen with UltraViolet A light) is used to treat moderate to severe psoriasis, as well as disabling psoriasis that cannot be controlled by other means. The drug psoralen is activated by the skin's exposure to ultraviolet light (UVA). PUVA can be used to treat the whole body or specific skin sites such as the hands and feet. It can also be combined with other antipsoriatic agents including topical and systemic therapies. PUVA is recommended for people who have moderate to severe psoriasis, or for those who have not improved on other therapies.

Methotrexate

Methotrexate (MTX) is an antimetabolite which is usually given orally for psoriasis or psoriatic arthritis. MTX can be very effective for clearing stubborn psoriatic lesions or alleviating the symptoms of psoriatic arthritis. Its use must be carefully monitored by a physician. It is used for the most serious and extensive cases.

Retinoids

The retinoid family of drugs is related to vitamin A. Etretinate (Tegison), which was the first oral retinoid to treat severe psoriasis, was phased out in 1998 in favor of acitretin (Soriatane). Acitretin is reserved to treat severe psoriasis. The U.S. Food and Drug Administration and Health Canada approved tazarotene (Tazorac) in 1997 and 1998. It was the first topical retinoid approved for the treatment of mild to moderate psoriasis. It is a water-based emollient gel.

Cyclosporin

Cyclosporin microemulsion (Neoral) is a new oral formulation of an older drug. It is effective in bringing about clearing of lesions for people who have severe psoriasis. When patients are placed on cyclosporin they must be carefully monitored.

Corticosteroids

Corticosteroids used to treat skin disease are most commonly available as a cream, ointment or solution.

It is important for the patient and their physician to be aware that the patient is using a corticosteroid product, and to carefully monitor such usage. The physician will also need to consider what type of treatment has or has not been of benefit in the past. In particular, the physician should determine what type of corticosteroids have been used previously and how long the patient used them.

Attached as Exhibit "D" is an excerpt from the USP/DI 1999 edition discussing corticosteroids. I am on the panel that developed and reviewed this monograph dealing with corticosteroids.

As a working rule, the patient should be advised by the physician to use as little corticosteroid as possible to bring about a reduction in the clinical signs and symptoms.

The topical application of corticosteroids brings about an alteration in function of the pituitary-adrenal axis. The corticosteroid diffuses across cell membranes and complexes with the cytoplasmic receptors. These complexes then enter the cell nucleus, bind to the DNA, and stimulate transcription of messenger RNA and subsequent protein synthesis of various inhibitory enzymes.

The side-effects of corticosteroids are well-documented.

Steroid-containing products applied to the skin can cause systematic absorption, flare-ups, cutaneous atrophy and stretch mark (striae) formation, thinning of the skin, and dilation of blood vessels (telangiectasia).

The very young and the elderly are particularly predisposed to increased absorption of topical corticosteroids because of less efficient adrenal reserve capacity and thinner skin, and in babies a high surface area to body volume.

Corticosteroids can cause changes to sleep patterns, bring about mood changes, and an increase in appetite. Excessive application of corticosteroids often result in suppression of the pituitary-adrenal axis, which translates in reduced adrenal activity and an inability on the part of the body to tolerate stress.

Corticosteroids can cause acne or increased hair growth to appear on the face or elsewhere.

Perioral dermatitis or rosacea may develop after the application of a topical steroid to the face.

Corticosteroids should not be used by pregnant women because of possible fetal abnormalities.

Corticosteroids should not be used around the eyes, or eyelids because of the risk of creating increased intra-ocular pressure/glaucoma.

Topical application of corticosteroid can suppress the body's ability to produce its own hormones which are needed to fight infection or deal with traumatic injury. As such, use of corticosteroids can cause or exacerbate certain types of infections.

The use of corticosteroid may cause the more common form of plaque psoriasis to convert to pustular psoriasis. Such a change may necessitate hospitalization and may be life-threatening.

Other untoward systemic side effects of using a corticosteroid include: skin pigmentary changes, increased blood pressure, Cushing's syndrome, folliculitis, furunculosis, the worsening or unmasking of diabetes, osteoporosis, impaired wound healing, allergic contact dermatitis, muscular wasting, and behavioral changes such as mania and psychosis.

Side effects increase with: (1) the potency of the corticosteroid, (2) length of treatment, (3) the amount used, and (4) the amount of body surface to which the drug is applied.

Continued use of a corticosteroid product frequently results in a tachyphylactic effect, in which the skin needs more and more of the product to achieve the same result.

Adverse effects can become apparent and even progress after the discontinuation of corticosteroid treatment.

To suddenly stop using a corticosteroid-containing product frequently causes other serious clinical sequelae. The most common and distressing problem is a "rebound" flare-up or an extension of the psoriasis.

CLOBETASOL

Of the twenty-three topical corticosteroids available, clobetasol is classified by the key rating systems as having a very high potency.

Clobetasol, being a very high potency corticosteroid, should only be used in small amounts, in localized areas, for a short period of time.

The regulatory agencies give the following skin diseases as their official labelled indications for use of clobetasol: (1) thick chronic lesions, (2) lichen simplex chronicus, and (3) discoid lupus erythematosus.

The use of clobetasol is contraindicated for use on children under 12 years old.

The leading national regulatory agencies - U.S. Food and Drug Administration, Medical Control Agency (London) and the Health Protection Branch (Ottawa)- only recommend dosage of clobetasol of 0.05%.

Good clinical practice would suggest that treatment with clobetasol be in the range of a week to 10 days. If the patient does not improve within a week, the patient should check with their doctor. These stringent advisories are to protect the patient from adverse systemic effects due to absorption and from skin atrophy.

Attached as Exhibit "E" is an excerpt discussing corticosteroids and clobetasol from a draft text manuscript entitled Drug Therapy and The Skin by Maddin, Ho, McLean and Rivers. This text is expected to be published in 2001.

PAYMENT FOR TREATMENT

If prescribed by a physician, the cost of such medications are usually covered by the patient's provincial or private plan. Other agents for treating psoriasis are classified as OTC (over the counter) and are purchased by the patient. If the patient seeks treatment that is not prescribed by a physician, they will usually be require to pay for same out of their own pocket.

MIRALEX SKIN CREAM

Attached as Exhibits "F" are marketing material and website extracts produced by the Defendants.

Attached as Exhibit "G" is a package of material produced by Health Canada. I am informed by Mr. Branch that this material was obtained pursuant to an access to information request. As can be seen from this documentation, Health Canada issued a warning and border alert in relation to the Miralex Skin Cream on November 18, 1999.

The documentation produced by Health Canada states that their testing revealed the presence of clobetasol at 0.095% in the Miralex Skin Cream. As noted above, the potency of the prescription medicine containing clobetasol is 0.05%. A cream containing clobestasol at 0.095% poses a serious health risk to users.

CLASS SIZE

The overall prevalence of psoriasis in the population is 1-3%. I have no personal knowledge of the number of persons who used the Miralex Skin Cream. However, attached as Exhibit "H" is a release from the U.S. National Psoriasis Foundation which quotes a Health Canada official as estimating that 4000 sales occurred since 1996, with 10% of these going to the United States and other countries.

______________________________
STUART MADDIN

SWORN BEFORE ME at the City of Vancouver, in the Province of British Columbia, this __________ day of May, 2000

______________________________
A Commissioner for taking Affidavits for British Columbia