Betamethasone

Abstract

A combination of multiple agents is often required to achieve treatment success for plaque-type psoriasis. We report a case series of 10 patients that were treated with betamethasone valerate foam (0.12%) in the morning and topical tazarotene cream (0.1%) in the evening for a total of 12 weeks or until plaques cleared. Erythema, scale, and thickness along with an aggregate severity score were determined at weeks 4, 8, and 12. One patient was lost to follow-up. Eight of the other 9 patients experienced improvement in their disease by week 12. Two patients were clear of their psoriasis at week 4 and 4 were clear at week 8. No adverse events, including irritation were reported; the use of the corticosteroid foam may protect against potential local irritation reported with tazarotene. The combination of tazarotene cream and betamethasone valerate foam is an effective combination approach to treating localized plaque-type psoriasis.

**********

Introduction

Tazarotene (Tazorac[R]) is a topical acetylenic retinoid that was FDA approved for the treatment of plaque psoriasis in 1997. Tazarotene is available in two vehicles, cream and gel, and comes in two concentrations, 0.1% and 0.05% and is effective for the treatment of mild-to-moderate plaque-type psoriasis. (1,2) Although its mode of action is still uncertain, tazarotene is believed to exert its effect through reduction of keratinocyte hyperproliferation, stabilization of atypical keratinocyte differentiation, as well as inhibition of pro-inflammatory markers. (3) The most common adverse events related to the use of tazarotene products include reversible skin irritation (ie, burning, erythema, and pruritus). (4) In addition, women of childbearing age should be alerted about the teratogenic potential of retinoids; thus, its use is contraindicated in pregnant women.

Betamethasone valerate (BMV) foam, 0.12% (Luxiq[R]) is a mid-potency topical corticosteroid effective for scalp and non-scalp psoriasis. (5) Its formulation as a foam vehicle lends cosmetic appeal. Compliance with topical regimens is an important factor for treatment success and many people prefer foams to ointments. (6,7) As with long-term use of any corticosteroid, there is the risk of skin atrophy and, if used in large quantities, suppression of hypothalamic-pituitary-adrenal axis.

Combining multiple topical medications is a common approach to psoriasis therapy. Combination therapy may enhance efficacy as well as safety. Tazarotene is effective as monotherapy as well in combination regimens with other treatment modalities. (8-10) BMV foam, to our knowledge, has only been reported as monotherapy; it is expected that the combination BMV foam and tazarotene will have efficacy in treating localized plaque psoriasis. The application of the BMV could help to prevent or limit the irritation seen when tazarotene is used as monotherapy. We present a case series of ten patients who had localized plaque psoriasis and demonstrated improvement in their disease while using a combination of tazarotene cream, 0.1%, and BMV foam.

[FIGURE 1 OMITTED]

Methods

Ten patients with stable, localized plaque-type psoriasis involving either a knee or an elbow were examined, treated, and evaluated in a private dermatology office by one author (SD); there was no control population. Patients were excluded if they had been previously using any agent other that topical emollients. The patients were treated with tazarotene cream once daily in the morning and BMV foam once daily in the evening. Evaluations occurred at weeks 4, 8, and 12 and consisted of the assessment of individual plaque characteristics of erythema, thickness, and scale and were graded on a 0 to 4 scale (0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = extreme). An aggregate severity score (the sum of the erythema, thickness, and scale) was calculated for each patient at each evaluation point. A reduction of 2 points in one of the individual plaque characteristics or 4 points in the aggregate score was considered clinically significant. Treatment continued until week 12 or clearance of the plaque was obtained. During that period the exposure to therapeutic doses of ultraviolet light and use of other anti-psoriatic medication was prohibited. Topical emollients were allowed.

Results

Ten patients initiated treatment; one patient was lost to follow-up; two patients missed their fourth week follow-up appointment. The tazarotene cream/BMV foam combination did not produce any adverse effects during the treatment course; specifically, there were no complaints of skin irritation, burning, pruritus, or erythema.

After 4 weeks of treatment 3/9 (33%) had experienced significant improvement in aggregate severity scores; 5 additional patients had significant improvement by week 8. There was no significant worsening of aggregate scores during the study interval as 8 of 9 patients (89%) had significant improvement at the study's end compared to baseline (figure 1). One patient did not have any improvement in aggregate or individual scores. Regarding individual plaque characteristics, scale and plaque thickness improved more than erythema as seen in a significant reduction in mean scores of both these parameters by week 8, which was maintained at week 12 (figure 1). Two patients had complete clearance of the treated lesions after only 4 weeks of therapy; 4 patients were clear at week 8, and 4 patients were clear at week 12. One of the patients who achieved clearance by week 4 maintained clearance at week 12. Two patients who achieved complete clearance at week 4 or 8 had slight worsening at week 12, but did not relapse to 50% of their baseline scores.

Discussion

Both of the topical agents investigated in this study, tazarotene (11) and BMV foam (12) are effective for the treatment of plaque psoriasis. The theory behind using betamethasone foam in combination with tazarotene for psoriasis is manifold: minimize the potential for skin irritation and atrophy and enhance efficacy by 1) using two drugs with differing mechanisms and 2) improving compliance. Tazarotene was found to be chemically compatible with a range of topical corticosteroids, which curtails a concern about its potential inactivation. (13)

There is a common belief that in order to control psoriasis, ointments lacking cosmetic appeal have to be used. It is also commonly believed that although topical retinoids may be effective for psoriasis, they must be applied in tandem with greasy ointments to avoid excessive dryness and skin irritation. The use of corticosteroid foam with tazarotene has not been previously documented and is a novel approach to combination therapy. Our data shows that the combination of tazarotene cream with betamethasone foam is effective. It is important to note that moisturizing with greasy ointments is not required to reduce the irritation linked with topical retinoids; most likely the anti-inflammatory effect of the BMV foam protected against this. The BMV foam is thought to have superb compliance as seen in patients' willingness to apply the foam regularly. (14) The cosmetic appeal of the BMV foam/tazarotene combination and the lack of irritation perhaps played a key role in fostering compliance with the resultant high efficacy that was seen.

There was excellent clinical response to the regimen used in this study although interpretation of case series data is obviously limited by the lack of a control group. There was also no blinding and there is the potential for investigator bias. Certainly a 12-week case series is not powered to adequately detect uncommon adverse events; however, irritation is commonly seen when topical tazarotene is used by itself, and this common event was not detected in our study. The authors recognize the need for a controlled trial to determine the full utility of the tazarotene/BMV foam regimen. An effective and pleasant combination regimen that uses a non-greasy corticosteroid foam along with a topical retinoid would certainly be appreciated by more that a few frustrated psoriasis patients.

Disclosure: This study was supported by a grant from Connetics Corporation. Dr. Feldman has received research, speaking and/or consulting support from Connetics.

References

1. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol. 1997;37:85-92.

2. Krueger GG, Drake LA, Elias PM, et al. The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis. Arch Dermatol. 1998;134:57-60.

3. Duvic M, Asano AT, Hager C, Mays S. The pathogenesis of psoriasis and the mechanism of action of tazarotene. J Am Acad Dermatol. 1998;39:S129-S133.

4. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol. 1997;37:85-92.

5. Franz TJ, Parsell DA, Halualani RM, Hannigan JF, Kalbach JP, Harkonen WS. Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and efficacy. Int J Dermatol. 1999;38:628-32.

6. Feldman S, Housman T. Patients' vehicle preference for corticosteroid treatments of scalp psoriasis. Am J Clin Dermatol. 2003;4:221-4.

7. Housman TS, Mellen BG, Rapp SR, Fleischer AB Jr, Feldman SR. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis. 2002;70:327-32.

8. Bowman PH, Maloney JE, Koo JY. Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel versus clobetasol ointment in the treatment of plaque psoriasis: a pilot study. J Am Acad Dermatol. 2002;46:907-13.

9. Gollnick H, Menter A. Combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis. Br J Dermatol. 1999;140 Suppl 54:18-23.

10. Lebwohl M, Poulin Y. Tazarotene in combination with topical corticosteroids. J Am Acad Dermatol. 1998;39:S139-S143.

11. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol. 1997;37:85-92.

12. Stein LF, Sherr A, Solodkina G, Gottlieb AB, Chaudhari U. Betamethasone valerate foam for the treatment of nonscalp psoriasis. J Cutan Med Surg. 2001;5:303-7.

13. Hecker D, Worsley J, Yueh G, Lebwohl M. In vitro compatibility of tazarotene with other topical treatments of psoriasis [In Process Citation]. J Am Acad Dermatol. 2000;42:1008-11.

14. Gottleib AB, Ford RO, Spellman MC. The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions. J Cutan Med Surg. 2003;7:185-92.

Sunil S. Dhawan MD, (a) Marianna L. Blyumin MD, (b) Daniel J. Pearce MD, (b) Steven R. Feldman, MD (b,c,d)

a. Department of Dermatology, Stanford University School of Medicine

b. Department of Dermatology, Wake Forest University School of Medicine

c. Department of Pathology, Wake Forest University School of Medicine

d. Department of Public Health Sciences, Wake Forest University School of Medicine

Address for Correspondence

Steven Feldman, MD, PhD

Wake Forest University School of Medicine

Department of Dermatology

Medical Center Boulevard

Winston-Salem, NC 27157-1071

Phone: 336-716-2768

Fax: 336-716-7732

e-mail: sfeldman@wfubmc.edu

COPYRIGHT 2005 Journal of Drugs in Dermatology, Inc.
COPYRIGHT 2005 Gale Group