Provisional Patent Application Serial No. 60/049,385, filed on June 11, 1997, in the name of John Sefton and Deborah A. Lew-Kaya.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method of treating psoriasis in humans with Tazarotene, preferably a gel comprising 0.1%, Tazarotene by weight, and phototherapy, i.e. UVB phototherapy. The Tazarotene gel may be topically administered followed by UVB phototherapy at the rate of three treatments per week.

2. Description of Related Art Psoriasis is a chronic skin disease which is known to be difficult to treat. Psoriasis is characterized by discrete and confluent, reddish, silvery-scaled maculopapules. These psoriatic lesions occur most often on the elbows, knees, trunk and scalp. Current treatment for psoriasis include the use of agents such as anthralin (dihydroxyanthralin), azarabine, colchicine, fluorouracil, methorexate, methoxsalen (8- methoxypsoralen), resorcinol, retinoids (for example, retinoic acid), corticosteroids (for example, clobetasol

propionate, trimcinolone acetonicde and the like), cyclosporin, iodochlorhydroxyquin, salicyclic acid, vitamin D, dapsone, somoatostatin, sulfur, tars and zinc oxide. Ultra-violet light treatment, alone or in combination with other agents such as psoralen (i.e., PWA treatment), is also used to treat psoriasis.

It is also known to treat skin diseases such as psoriasis, seborrheic dermatitis and eczema with sunlight baths or ultraviolet (W) baths with lesions painted with a solution of coal tar, anthralin or/psoralens (See U.S. Patent Numbers 5,681,593 and 5,122,514). Other references suggesting photo therapeutic treatment of proliferative skin diseases, such as psoriasis, include U.S. Patent 4,753,958, wherein W light is utilized in combination with phototoxic derivatives of hematoporphyrin. See also U.S. Patent 5,556,612 wherein optical radiation is combined with a topical sunscreen to provide preferential photoprotection in phototherapy, photochemotherapy and photodynamic therapy.

Various devices for providing W radiation for treating skin diseases such as psoriasis are disclosed in U.S. Patents 4,177,384; 4,287,554; 4,370,595 and 4,560,883 which are hereby incorporated by reference in their entirety to disclose devices which may be used to carry out the method of the present invention.

The safety, efficacy, and patient acceptability of tazarotene 0. 1 k and 0.05 k gels when used in the treatment of psoriasis were evaluated in two phase 3 clinical research studies. Based on promising results from these studies, Allergan, Inc. filed a new drug application for tazarotene in June, 1995 which was approved by the Food and Drug Administration (FDA).

BRIEF SUMMARY OF THE INVENTION The present invention provides a method for treating psoriasis in a human subject by topically applying to the psoriasis of said subject an effective amount of tazarotene and an effective amount of WB radiation.

Preferably, in the method of the invention, tazarotene is applied as a 0.05% or 0.1k by weight, gel.

In the preferred method of the invention, tazarotene is administered once daily in the evening.

Preferably, the UVB phototherapy is administered by means of a Houva 11 UVB Box, which is available from National Biological Corporation.

BRIEF DESCRIPTION OF THE DRAWING FIGURES Figure 1 compares the reduction in plaque achieved by the method of the present invention, i.e. the combination of treatment with tazarotene and WB radiation, and WB radiation treatment, alone.

Figure 2 compares the reduction in scaling achieved by the method of the present invention, i.e. the combination of treatment with tazarotene and WB radiation, and WB radiation treatment, alone.

Figure 3 compares the reduction in erythema achieved by the method of the present invention, i.e.

the combination of treatment with tazarotene and WB radiation, and WB radiation treatment, alone.

Figure 4 compares the treatment success rate achieved by the method of the present invention and WB radiation treatment, alone.

Figure 5 compares the reduction in plaque achieved by the method of the present invention and WB radiation treatment, alone, and UVB radiation treatment in combination with placebo, i.e. the tazarotene vehicle.

Figure 6 compares the reduction in scaling achieved by the method of the present invention and WB radiation treatment, alone, and UVB radiation treatment in combination with placebo, i.e. the tazarotene vehicle.

Figure 7 compares the reduction in erythema achieved by the method of the present invention and UVB radiation treatment, alone, and WB radiation treatment in combination with placebo, i.e. the tazarotene vehicle.

Figure 8 compares treatment success rate achieved by the method of the present invention and WB radiation treatment, alone, and UVB radiation treatment in combination with placebo, i.e. the tazarotene vehicle.

DETAILED DESCRIPTION OF THE INVENTION The preferred tazarotene gel for use in the method of this invention is disclosed in U.S. Patent Application Serial No. 623,184, which is entitled "Stable Gel Formulation for Topical Treatment of Skin Conditions", which was filed on March 28, 1996, in the name of Prakash Charu and is hereby incorporated by reference in its entirety. (Said preferred gel is also described in published PCT Application No.

PCT/US95/07338 or WO 95/33489.) A method for preparation of a gel formulation of tazarotene for topical treatment of psoriasis comprises the steps of: 1) mixing purified water, edetate disodium, ascorbic acid and Carbomer 934P i.e. a polymer of

acrylic acid crosslinked with allyl ethers of sucrose, until the carbomer is dispersed to form a part I; 2) mixing purified water, Poloxamer 407, i.e. a- <BR> <BR> <BR> <BR> Hydro-co -hydroxypoly ( oxyethylene ) .-poly (oxopropyl ene ) b <BR> <BR> <BR> <BR> <BR> poly(oxyethylene) a block polymer, wherein the average value of a is 101 and the average value of b is 56, to form a part II; 3) adding part II to part I and homogenizing part I and Part II; 4) mixing polyethylene glycol, Polysorbate 40, i.e. polyoxyethylene 20 sorbitan monopalmitate, hexylene glycol, butylated hydroxytoluene and butylated hydroxyanisole and heating to dissolve same; 5) cooling the mixture of step 4) to room temperature and adding benzyl alcohol and tazarotene thereto to form a part III; 6) mixing purified water and tromethamine to form part IV; 7) adding part III to parts I and II while stirring and thereafter adding part IV with mixing until homogeneous.

Both the 0.05% and the 0.1%, by weight, tazarotene gel formulations are available from Allergan, Inc. of Irvine, CA under the brand name Tazorac.

DESCRIPTION OF THE PREFERRED EMBODIMENT The hypothesis for the study described below was that Tazarotene plus UVB, as compared to WB plus vehicle or UVB alone would work faster, have higher success rate, require less WB exposure and be well tolerated. The Study objective was to assess safety and efficacy of pre-treatment with Tazarotene 0.1k gel and UVB phototherapy in comparison with the Tazarotene

vehicle (placebo) and WB phototherapy and WB phototherapy, alone, for 10 weeks. During WB phototherapy, topical agents were applied three times weekly to the target lesion by the phototherapy nurse.

The study was a multicenter, investigator-masked study including 60 subjects and 120 target lesions. During the two-week pre-WB phototherapy period the patients were randomly assigned to receive two of the following treatments: Tazarotene 0.1% gel once a day; vehicle gel once a day; or no treatment. The topical agents were applied once daily. Prior to WB therapy, the minimal erythemal dose (MED) was assessed using a range of 20 mJoules/cm2 up to 100 mJoules/cm2. Initial starting WB dose is 25% of MED. If MED is immeasurable, starting dose is 25 mJoules/cm2. During the ten-week WB phototherapy period the patients were treated with WB therapy three times a week and topical therapy three times weekly (0.1% Tazarotene gel, vehicle gel, or no treatment) administered by the phototherapy nurse after UVB exposure. Study population was as follows: male or non-reproductive female; 18 years or older; stable plaque psoriasis; two bilaterally symmetrical plaques accessible to phototherapy; not exceeding 50% of TBS; baseline plaque elevation of at least four (moderate, in 0-8 scoring system); no oral retinoid within two months; no excessive vitamin A intake; no oral psoriatic therapy (other than retinoid) or PWA within one month; no WB within two weeks; no significant systemic disease or immunosuppression. The WB exposure was increased until either improvement in psoriasis was noted or MED was reached. If one target lesion reached MED earlier than the other, a photo-opaque covering was applied to the former so the latter site could still be treated with a higher dose of WB irradiation. If both target lesions

cleared, WB was discontinued. If one target lesion cleared and the other shows 2 75% improvement, WB was discontinued.

The following evaluation criteria was used: Efficacy Variable Plaque elevation, scaling, erythema: Grading Scale 0 = none, 2= mild, 4=moderate, 6=severe, 8=very severe (with whole-point increments (1, 3, 5, 7) serving as mid-points) Global response to treatment Total cumulative WB exposure (mJoules/cm2) Global Response to Treatment Treatment success is defined as moderate response or better.

0: Completely cleared 1: Almost cleared about 90% improvement 2: Marked response about 70% improvement 3: Moderate response about 50% improvement 4: Slight Response about 25% improvement 5: Condition Unchanged 6: Condition Worsened 10 patients were enrolled in the study. The patients that we used in the study had the following demographic constitution: Ten male patients Mean Ranee Age (years) 48 27-67 Weight (kg) 91 61-134 Height (cm) 180 173-193

Race Caucasian 8 Black 1 Hispanic 1 Nine patients completed the study. One was discontinued due to WB burn, not as a result of the topical- treatment.

The results are reported in the following figures.

The reduction in plaque, scaling and erythema are reported in Figures 1 through 3, respectively. Note, in each case Tazarotene in combination with treatment with WB was more effective than WB treatment alone.

As shown in Figure 4, the treatment success rate with Tazarotene and WB phototherapy was 100% by day 81.

At the same time, WB phototherapy, alone, showed only about a 60% success rate.

In Figures 5 through 8, the reductions in plaque, scaling and erythema, respectively, are greater with Tazarotene and WB treatment, than with either WB, alone, or WB with vehicle (placebo).

In Figure 8 both Tazarotene and WB treatment and vehicle and WB treatment show a 100% success rate at 81 days. However, the treatment with Tazarotene and WB achieves a successful treatment more quickly than vehicle and WB treatment. For example, at day 53, about 90% success is achieved with Tazarotene and WB, while about 30% success is achieved with vehicle and WB.

The following adverse events were reported during the study: Tazarotene Vehicle Perilesional irritation 2 0 Perilesional tenderness 0 1 Lesional irritation 0 1 Burning sensation 1 0 Itching 1 0 All were mild in severity In conclusion, treating psoriasis in humans with a combination of Tazarotene and WB phototherapy is more effective than a combination of the Tazarotene vehicle and WB phototherapy or WB phototherapy, alone.

The following conclusions were reached in this study. Reductions in plaque elevation and scaling were generally greater for plaques treated with WB plus Tazarotene 0.1% gel. Less time was required to reach treatment success for plaques treated with WB plus Tazarotene 0.1% gel. Combination therapy was well tolerated and no significant WB-Tazarotene phototoxicity noted.

While particular embodiments of the invention have been described it will be understood of course that the invention is not limited thereto since many obvious modifications can be made and it is intended to include within this invention any such modifications as will fall within the scope of the appended claims.