Feature: Treating Psoriasis Patients: A Topical Therapy Update - By John Y. Koo, M.D., and Khanh D. Nguyen, M.S. A look at recent developments in topical therapies for psoriasis. I n recent years, there have been a number of new treatment modalities developed to better treat psoriasis — especially moderate to severe cases. Many new uses for existing topical therapies have been developed, and there’s new data to support new combination therapies. Here, these experts take a look at what topical therapies are at your disposal to help psoriasis sufferers. Calcipotriene (Dovonex). In the United States, Europe and Canada, calcipotriene/calcipotriol (Dovonex) remains the most prescribed single agent for the treatment of psoriasis. This agent is primarily used in combination or sequential therapy, especially with halobetasol propionate (Ultravate). In the United States, the FDA has now approved the following: • the sequential therapy of psoriasis using the com- bination of halobetasol propionate in step one (“clearing phase”) or as weekday-weekend “pulse” therapy in step two (“transitional phase”) and as monotherapy in step three (“maintenance phase”).1 New data demonstrate that calcipotriene cream can help reduce the frequency of UVB phototherapy required to attain a defined level of improvement.2 The study, a multi-center, double-blind study conducted in Canada, followed 164 patients. The study assessed the effectiveness of calcipotriene cream in conjunction with UVB therapy. During the study, the arms of 80 patients underwent a combination of UVB three times per week and a placebo cream consisting of the vehicle of calcipotriene. The results from these patients were compared with 84 others who received UVB twice a week and calcipotriene cream twice a day. After 12 weeks of treatment, the clinical outcome was essentially similar between the two groups — despite the significantly decreased cumulative exposure to UVB phototherapy among the patients who received active cream as compared to the placebo cream (1,570 mJ/cm2 in the former group as compared to the 5,430 mJ/cm2 in the control group). The clinical implications of this finding are not trivial because many patients are active and working, making it difficult to have phototherapy three times per week. Patients also using calcipotriene cream may receive adequate therapeutic benefit, even if they only undergo UVB phototherapy two times per week. Psoriasis Patient 1 Enhancing Systemic Agents Calcipotriene has also proven beneficial for enhancing the efficacy of two other drugs. In previous double-blind, randomized studies, calcipotriene ointment showed clear benefits over placebo ointment in enhancing the effectiveness of ecitretin (Soriatane) and low-dose cyclosporine (Neoral).3,4 Recently, data from the Netherlands attested to the benefit of adding calcipotriene ointment over placebo ointment in enhancing the efficacy of methotrexate.5 The same study also showed that continued use of calcipotriene ointment is more effective in preventing relapse than the continued use of the placebo ointment after methotrexate was discontinued. In the first stage of this study, 98 psoriatic patients were randomly divided into two groups. One group of patients received calcipotriene ointment twice a day — the other received a placebo ointment. All patients were given doses of methotrexate that were adjusted to obtain marked improvement of their psoriasis. The group that received the calcipotriene ointment required an average dosage of methotrexate of only 6.5 mg per week to achieve marked improvement or clearance of psoriasis whereas the placebo group required, on average, 10.5 mg per week of methotrexate to get similar results. Once patients achieved marked improvement or clearance, methotrexate was abruptly discontinued and they were maintained on respective topical agents. After 6 months, fewer patients who received the active agent suffered no relapses — 30.8% compared with only 8.7% of those who received the placebo ointment. The relapse was defined as the point in time when the psoriasis severity score doubled after methotrexate was discontinued. Combination Therapy with Tazarotene (Tazorac) Tazarotene is probably underutilized because many of us became discouraged by its irritation potential and its limited efficacy as a monotherapy. However, the combination of tazarotene with mometasone furoate (Elocon) cream has greater efficacy than tazarotene 0.1% gel alone.6 A multi-center study compared tazarotene 0.1% gel in combination with mometasone cream to the use of mometasone cream twice a day and found that the combination was not only more efficacious, but resulted in longer remission.7 For this study, 73 patients were randomly broken into two sections. The first group received a combination of tazarotene and mometasone cream once a day. The second group received mometasone cream twice a day. During the 12-week treatment period, the combination therapy showed a statistically significant favorable advantage. During the post-treatment, follow-up phase, patients had significantly fewer incidences of relapse when treated with the combination. Four weeks after treatment ended, 68% of the patients had used mometasone cream twice a day dropped out of the study because of psoriasis flare while only 12% of the combination group discontinued due to disease flare. This difference was significant at p<0.001 level. Sidebar 1 How to Decrease the Irritation Potential of Tazarotene To decrease irritation risk while maintaining efficacy with tazarotene therapy, you may need to use “short-contact” tazarotene therapy. Initially, apply tazarotene 0.1% gel to psoriatic plaques for as little as 1 minute. Gradually increase the duration of application by 1 minute up to several minutes. A series of clinical case studies has shown that this short-contact approach appears to retain much of the efficacy while minimizing irritation.8 In the short-contact application, advise patients to apply the cream to the thickest plaques first and the thinnest plaques last, so that the thicker plaques experience longer exposure than the thinner ones. Combining Tazarotene and Calcipotriene Using these two drugs has been shown to be well tolerated and possibly synergistic in an open- labeled, bilateral comparison study involving 15 patients.9 In this study, calcipotriene ointment was applied twice a day on one side along with the application of tazarotene 0.1% gel once a day. In one of the applications, both agents were applied together. The other side received clobetasol ointment twice a day. In this 2-week study, the overall efficacy proved to be essentially identical, even though the side that was treated with clobetasol ointment demonstrated faster resolution of erythema than the side that was treated with the two non-steroids. In this limited study, only mild perilesional irritation was noted on the side that was treated with the two non-steroids. The fact that overall efficacy was essentially equivalent to clobetasol ointment strongly suggests that calcipotriene and tazarotene are both compatible and synergistic when applied together. More Effective Phototherapy Tazarotene 0.1% gel also appears to significantly enhance the efficacy of UVB phototherapy that is performed three times per week, according to an article published in the Journal of American Academy of Dermatology.10 The article highlighted results from a multi-center, randomized trial in which three treatment scenarios were tested. The first group of patients applied tazarotene 0.1% gel to psoriatic plaques on one of their arms and underwent UVB phototherapy three times a week. For the second group, lesions were treated with UVB three times per week with the vehicle of tazarotene gel. In the third group, patients’ plaques were treated with UVB phototherapy alone. During the 2 weeks prior to starting UVB phototherapy, patients’ lesions were treated with tazarotene 0.1% vehicle gel or nothing. This was followed by 10 weeks of aggressive UVB phototherapy conducted three times per week. Topical agents were applied once a day during the pre-UVB phototherapy time period, but only three times per week during the 10 weeks UVB phototherapy. Patients who underwent UVB phototherapy with tazarotene 0.1% gel showed greater improvement than the groups that received treatment with UVB phototherapy plus vehicle or UVB phototherapy alone. The difference between the results with the combination group and UVB-only group was statistically significant at p<0.05 level. In addition, the accumulative UVB exposure required to reach treatment success, defined as a 50% improvement in psoriatic plaques, was much less in the combination group. These patients needed only 390 mJ/cm2 to achieve success, compared with 1,394 mJ/cm2 for the patients who received UVB therapy plus a vehicle group and 1,644 mJ/cm2 for patients who underwent UVB phototherapy alone. No unusual photosensitivity was observed in any of the combination patients. Because aggressive three-times per week UVB phototherapy was conducted, in comparison to the earlier study with calcipotriene and UVB phototherapy, the result of this study suggests that tazarotene enhances UVB phototherapies better than calcipotriene cream. Lastly, tazarotene is now available in cream formulation, which has proven to have efficacy as good as the gel formulation, a much better emollient base and a tendency toward less irritation. In addition, the cream showed a better remission rate than the gel in a clinical trial with a 12-week treatment phase and 12-week post treatment observation phase. Based on these results, I’d recommend avoiding the gel formulation of tazarotene to treat psoriasis, except possibly for scalp and nail applications. Psoriasis Patient 2 Continued Advances These developments have proven to be effective in better treating psoriasis patients. It’s important to continue to investigate new and better treatment options in the future so that we can continue to serve our patients with the most up-to-date expertise and skills in the fight against psoriasis. 1.Koo, J.Y.M., How and why to use sequential therapy for psoriasis. Skin Aging, 1998. 6(10): p. 42-6. 2.Ramsay CA, Schwartz BE, Lowson D, Papp K, Bolduc a, Gilbert M, Calcipotriol cream combined with twice weekly broad band UVB phototherapy: a safe, effective and UVB-sparing antipsoriatric combination treatment. Dermatology, 2000. 200: p. 17-24. 3.Van de Kerdhof PCM, Cambazard F, Hutchinson PE, Haneke W, Wong E, Souteyrand P, Damstra RJ, Combemale P, Neumann MH, Chalmers RJ, Olsen L, Revuz J., The effect of the addition of calcipotriol ointment (50 m/g) to acitretin therapy in psoriasis. Br J Dermatol, 1998. 138: p. 84-9. 4.Grossman RM, Thivolet J, Claudy A, Souteyrand T, Guihou JJ, Thomas P, et al., A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: Results of a multi-center placebo-controlled study. J Am Acad of Dermatol, 1994. 31: p. 68-74. 5.Elke MC, De-jong J, Department of Dermatology University Hospital Nijmegen, Netherlands. 6.Lebwohl MG, Breneman DL, Goffe BS, et al., Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis. J Am Acad of Dermatol, 1998. 39: p. 590-6. 7.Koo J, Martine D, Investigator-masked comparison of tazarotene gel q.d. plus mometasone furoate cream q.d. vs. mometasone furoate cream b.i.d. in the treatment of plaque psoriasis. International J of Dermatol, 2001. 40: p. 210-215. 8.Persaud A, Bershad S, Lamba S, Lebwohl M., Short-contact tazarotene therapy for psoriasis. Poster presented at the Academy 2000 meeting of the American Academy of Dermatology, Nashville, Tennessee, 2000. 9.Bowman P , Koo J, J Am Acad of Dermatol, in press. 10.Koo John, Lowe NJ, Lew-Kaya DA, Alexandra, Vasilopoulos I, Lue JC, SeftonJ, and Gibson JR., Tazarotene plus UVB phototherapy in the treatment of psoriasis. J Am Acad of Dermatol, 2000. 43(5): p. 821-8. 11.Koo J and Lebwohl M, Duration of remission of psoriasis therapies. J Am Acad of Dermatol, 1999. 41: p. 51-9. 12. Menter A, Cram DL, The Goeckerman regimen in two psoriasis day care centers. J Am Acad of Dermatol, 1983. 9: p. 59-65. 13.Collins P, Wainwright NF, Amorin I, LakshmipathiT,Ferguson J., 8-MOP PUVA for psoriasis: a comparison of minimal phototoxic dose-based regimen with a skin-type approach. Br J Dermatol, 1996. 135: p. 248-54. 14.Stern RS, Armstrong RB, Anderson TF, Bickers DR, Lowe NJ, Harber L, Voorhees J, Parrish FA, Effect of continued ultraviolet B phototherapy on the duration of remission of psoriasis: a randomized study. J Am Acad of Dermatol, 1986. 15: p. 546-52. 15.Kaplan RP, Russell DH, Lowe NJ, Etretinate therapy for psoriasis: clinical responses. J Am Acad of Dermatol, 1983. 8: p. 95-102. 16.Van Dooren-Breebe RJ, Kuijpers AL, Mulder J, De Boo T, Van de Derdhof PC, Interruption of long-term methotrexate treatment in psoriasis: evaluation of clinical course and laboratory parameters after discontinuation and reintroduction of weekly oral methotrexate. Acta Derm Venereol (Stockh), 1994. 75: p. 393-6. 17.Finzi AF, Mozzanica N, Pigatto PD, Cattanco A, Ippolito F, Carducci G, et al, Cyclosporine versus etretinate: Italian multi-center comparative trial in severe plaque-form psoriasis. Dermatology, 1993. 187(suppl 1): p. 8-18. 18.Ellis CN, Fradin MS, Messaria JM, Brown MD, Siegel MT, Hartley AH, et al, Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med, 1991. 324: p. 277-84. 19.Ellis CN, Fradin MS, Hamilton TA, Voorhees JJ, Duration of remission during maintenance cyclosporine therapy for psoriasis: relationship to maintenance dose and degree of improvement during initial therapy. Arch Dermatol, 1995. 131: p. 791-5. 20.Lebwohl MG, Ast E, Callen JP., Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis. J Am Acad of Dermatol, 1998. 38: p. 705-11. 21.Giannotti B, Carli P, Varotti C, et al., Treatment of psoriasis with calcipotriol: time onset and healing of relapses. Eur J Dermatol, 1997. 7: p. 275-8. Skin & Aging - ISSN: 1096-0120 - Volume 10 - Issue 3 - March 2002 - Pages: 35 - 39