Mild-to-Moderate Psoriasis - part 7 pot

but safer for long-term use. In sequential therapy, ‘‘rabbits’’ and ‘‘turtles’’ are paired in specific sequences to maximize both efficacy and safety. Sequential therapy embraces the value of providing rapid symptomatic relief to suffering patients while also emphasizing the importance of providing a strategy for safe, long-term control of their disease. This is typically accomplished in three phases: the clearing phase (Phase 1), which employs a rapid-acting or ‘‘quick fix’’ agent for fast relief; the transition pha se (Phase 2), the most challenging phase in which one attempts carefully, patiently, and creatively to have the ‘‘turtle’’ successfully take over from the ‘‘rabbit’’ without inciting worsening of psoriasis; and the maintenance phase (Phase 3), the goal of which is l ong-term c ontrol with minimal side e ffects ( Table 1). As the cleari ng phase agent i s usually a superpotent topical steroid, t here is a risk of rebound of psoriatic l esions while transitioning to the safer, less potent maintenance phase agent. The skillful combinational use of therapeutic agents and optimal timing of regimen changes during the transition phase can significantly reduce this risk and is essential to a success ful therapeutic course. With all of the therapeutic modalities currently available for psoriasis, the possibilities for sequential therapy schemes are endless and include systemic sequential therapy involv ing the newer biological agents as well as various phototherapy options. This chapter will only focus on the concept of sequential therapy using topical agents. The most common topical sequential therapy scheme in practice today will be described and used to illustrate the principles that guide clinicians in choosing among existing schemes as well as creating new schemes. The concept of sequential therapy using s ystemic or phototherapy modalities a re addressed in other publications. TOPICAL SEQUENTIAL THERAPY: CALCIPOTRIENE AND HALOBETASOL PROPIONATE The most commonly practiced topical sequential therapy scheme for psoriasis in the United States involves halobetasol propionate (Ultravate 1 ) ointment, a superpotent topical corticosteroid, and calcipotriene (Dovonex 1 ) ointment, a vitamin D analog (Table 2). The sequence entails application of halobetasol propionate once daily in the morning and calcipotriene once daily at bedtime for approximately one month (Phase 1, clearing phase), then calcipotriene twice daily on weekdays and halobetasol propionate twice daily on weekends for one month or longer (Phase 2, transition phase), and finally, calcipotriene twice daily until psoriasis completely resolves, at which time therapy can be tapered off (Phase 3, maintenance phase). This particular Table 1 Sequential Therapy Phase 1: Clearing phase !Phase 2: Transition phase !Phase 3: Maintenance phase 164 Koo and Colaco scheme has been chosen to illustrate the idea of topical sequential therapy because it is the only scheme in which the merit of each step has been validated by double-blind, randomized clinical trials directly comparing the various options. Calcipotriene has been shown through well-controlled studies to be a safe and effective treatment for psoriasis (1–5). For example, calcipotriene ointment was found in a double-blind, multicenter study to be superior to fluocinonide (Lidex 1 ) ointment, both in rate of improvement and degree of efficacy (6). It is not surprising that the frequency of calcipotriene and other vitamin D analogs used in the treatment of psoriasis falls second only to higher-strength topical corticosteroids. However, there are a significant number of dermatologists in the United States who question the effectiveness of calcipotriene after experiencing somewhat disappointing results with the medication when it was first introduced. This less than expected ‘‘real- life’’ efficacy of calcipotriene may stem from a few issues. First, it was not realized until years after introduction that the efficacy of calcipotriene is essentially halved and it has an even slower onset of action when it is used only once daily instead of twice daily (7). Unfortunately, most patients were using calcipotriene once daily at bedtime, as it was initially only available in an ointment formulation, which is less conducive to morning application. Interestingly, the efficacy of once-daily calcipotriene use approaches that of twice-daily use if it is continued for eight weeks. However, most patients (and their physicians) were disappointed by the slow onset of action, which is especially true of once daily use, and concluded that calcipotriene was not a useful medication long before eight weeks had passed. Second, a random string of calcipotriene nonresponders may have biased some dermatologists’ clinical impression of this medication. Third, calcipotriene could have caused disappointment when used to abruptly replace a superpotent topical steroid Table 2 Example of Topical Sequential Therapy Phase 1: halobetasol propionate qam, calcipotriene qhs Phase 2: pulse therapy, calcipotriene bid on weekdays, halobetasol propionate bid on weekends Phase 3: calcipotriene bid, then taper off Phase 1: clobetasol foam and calcipotriene bid Phase 2: pulse therapy, calcipotriene bid on weekdays, clobetasol foam and calcipotriene bid on weekends Phase 3: calcipotriene bid, then taper off Approximately 1 month Approximately 1 month Until psoriasis resolves completely !! Topical Sequential Therapy of Psoriasis 165 only to result in rebound of psoriatic lesions. Finally, the use of calcipotriene as monotherapy is associated with a 2% to 3% incidence of significant lesional and perilesional irritation, which is bothersome enough to patients that they discont inue use (8,9). The sequential use of calcipotriene and halobetasol propionate as described previously provides a solution to many of the aforementioned concerns. While superpotent topical steroids such as halobetasol propionate work very well, the combined use of topical steroids and calcipotriene appears to work even better. In fact, the two medications seem to be ideal partners. A double-blind, randomized, multicenter study found that, after only 14 days of therapy, the use of calcipotriene ointment in the morning and halobetasol propionate ointment in the evening was significantly more effective when compared to twice-daily monotherapy with either agent and also resulted in a lower incidence of irritation from calcipotriene (10). Addi- tional double-blind, randomized studies have also supported the finding that calcipotriene and corticosteroids work synergistically to enhance efficacy and result in fewer side effects than treatment with either agent alone (11). Moreover, the use of halobetasol propionate at the start of therapy can compensate for calcipotriene’s slow onset of action and cover patients who might be calcipotriene-slow or nonresponders. Finally, using calcipotriene in conjunction with halobetasol propionate may decrease the incidence of skin thinning from topical steroid use (12). Similar results were found using a combination of calcitriol, another vitamin D analog, and betamethasone valerate, another topica l steroid (13). The side effect profile of superpotent topical steroids makes them a poor choice for long-term control of psoriasis. This well-known fact is the rationale for the ‘‘weekday–weekend’’ regimen of the transition phase (Phase 2). The first regimen of this kind was introduced in the late 1980s by which the patient applies a potent topical steroid daily until flattening of the plaque occurs and then uses the steroid on weekends only (14). It has since been modified to include calcipotrien e after Lebwohl et al. (15) found that the addition of calcipotriene oin tment twice daily on weekdays to the use of halobetasol ointment twice daily on weekends resulted in nearly twice as many patients achieving a six-month remission and a decreased incidence of side effects associated with long-term topical steroid use. The use of this type of intermittent pulse dosing during Phase 2 allows clinicians to safely extend treatment of psoriasis with superpotent topical steroids. Pulse therapy also minimizes the risk of rebound by allowing superpotent topical steroids to be gradually tapered off rather than abruptly discontinued once psoriatic plaques have become macular. During the maintenance phase (Phase 3), the twice-daily application of calcipotriene alone (Phase 3) can be init iated once lesions have not only flattened but also the degree of erythema has decreased from red to pink. This calcipotriene dose may be gradually decreased to once daily, then once 166 Koo and Colaco every other day, and, ultimately, when psoriasis is no longer visible, all pre- scription medications can be discontinued. Of note, the calcipotriene molecule is relatively unstable and can be inactivated when combined with some topical medications, especially if an acidic environment is created (16). In the aforementioned study that demon- strated the superiority of using once-daily calcipotriene and halobetasol propionate to twice-daily monotherapy with either agent, the once-daily calcipotriene and halobetasol propionate ointments were applied separately, morning and night, in order to prevent inactivation of either agent (10). This is also true of the Phase 1 regimen presented in Table 2. Halobetasol propionate ointment and cream have since been found to be among the medications that are compatible with calcipotriene (17). Therefore, as calcipotriene and halobetasol propionate are individually known to have better efficacy when applied twice a day compared to once a day, the best theoretical regimen would be to use both calcipotriene and halobetasol propionate twice daily. The author recommends mixing the agents in one palm just prior to each application instead of premixing agents, as inactivation can begin as soon as 50 hours after mixing (17). Similarly, calcipotriene can be continued on weekends during Phase 2 pulse therapy, with halobetasol propionate applied in addition to calcipotriene. From common clinical experience, the simultaneous use of the two medications appears to work well, although clinical studies have yet to be performed. Recommending that patients mix calcipotriene and halobetasol propionate creams for morning application and the two ointment formulations for nighttime application may increase compliance. OPTIMAL TIMING TO PROCEED DOWN SEQUENTIAL THERAPY SCHEME The issue of timin g of each treatment phase can be approached i n two different ways. The first is to establish approximate timeframes for the individual treatment phases b ased on clinica l experience and p rior studies. Generally speaking, Phase 1 takes three to four weeks, Phase 2 t akes another m onth, and P hase 3 goes on ind efinitely or until psoriasis has completely resolved. Needless to say, patients’ lesions need to be assessed intermittently to ensure that th e ma jor ity of lesions are responding appropriately to treatment. If the patients’ lesions are improving faster or slower than the predicted timeframes, then transitioning between phases must be adjusted accordingly. For example, some patients with chronically active lesions may require indefinite pulse therapy (Phase 2). Fortunately, this ‘‘weekday–weekend’’ regimen appears to be remarkably safe. In my experience, patients do not have any significant skin atrophy on this r egimen as long as superpotent topical steroids are n ot applied more than two days per week or to the patient’s face, axilla, groin, and other sensitive areas. Adrenal suppression should not be a concern when topical steroids are used only two days per week. Topical Sequential Therapy of Psoriasis 167 The second approach to the issue of timing is more sophisticated but also seems to be more effective. Patients are instructed to transition therapy from Phase 1 to Phase 2 for plaques that have flattened and from Phase 2 to Phase 3 for flattened lesions in which the degree of erythema has decreased from red to pink. With this approach, treatment is individualized so that faster-responding lesions move quickly along the sequence and thick, recalcitrant plaques stay in Phase 1 for more time (w here induration obviates the concern for skin atrophy). SEQUENTIAL THERAPY AS A FLEXIBLE THERAPEUTIC STRATEGY The activity of psoriatic lesions is often unpredictable and therapeutic goals range from maintenance of long-term remission, control of acute flares, or even a period of treatment cessation if the severity of psoriasis decreases. Patients with this chronic disease can certainly benefit from individualized treatment plans. The advantage of sequential therapy is that the intensity of treatment can be easily adjusted to the level of activity of psoriasis. As their psoriasis improves, patients transition to the next phase, or if their psoriasis worsens (for example, during winter months), they can regress to an earlier treatment phase. Not only do patients appear to have better clinical outcomes with this flexible therapeutic strategy but they also appreciate the greater sense of control they feel ov er a disease that is known to unpre- dictably fluctuate in severity during its chronic course. SEQUENTIAL THERAPY WITH NEW TOPICAL STEROID FORMULATIONS One of the new, innovative formulations of topical steroids uses a foam vehicle to deliver medication. Foam is thermolabile and breaks down on contact with human skin. The result is drug delivery with minimal residue, quick absorption, and increased convenience of application. Furthermore, several in vitro studies have indicated that the foam formulation is a more efficient vehicle for topical drug delivery in comparison to traditional creams, ointments, and solutions (18–22). Clobetasol propionate (Olux 1 foam) is one of the topical steroids now available in a foam formulation. Clobetasol propionate foam, like other foam formulations, is quickly absorbed and leaves minimal residue, which makes it ideal for use in combination with other topical agents, such as calcipotriene. The foam vehicle is absorbed so quickly that there is no theoretical concern for dilution or incompatibility when combined with other therapeutic agents. The efficacy of clobetasol propionate foam and calcipotriene ointment when used in a topical sequential therapy scheme was recently evaluated in a clinical study (23,24). The first part of the study evaluated the 168 Koo and Colaco twice-daily use of clobetasol propionate foam and calcipotriene ointment as the clearing phase regimen (23). Eighty-six subjects were randomized to three groups: twice-daily monotherapy with clobetasol propionate foam, monotherapy with calcipotriene ointment, or combination therapy. Subj ects in the combination group were directed to apply calcipotriene ointment immediately after the clobetasol prop ionate foam was absorbed. After two weeks of treatment, reductions in psoriasis severity scores for the target lesions were significantly greater in the combination therapy group compared to either monotherapy group [clobetasol alone: p ¼ 0.0017 (trunk lesions) and p < 0.0001 (extremity lesions); calcipotriene alone: p < 0.0001 (both trunk and extremity lesions)]. With respect to the trunk psoriatic lesions, the combination therapy group achieved a 69.3% mean reduction in psoriasis severity scores, compared to 48.1% with clobetasol propionate foam alone and 36.6% with calcipotriene ointment alone. A similar pattern was seen with extremity lesions. The results also support in vitro data, as described earlier, suggesting that calcipotriene inactivation does not occur when it is applied immediately after a topical steroid foam (25). The results of the second phase of this sequential therapy study were reported at the 2005 Annual American Academy of Dermatology meeting (24). The second phase involved 38 subjects who achieved at least a 50% reduction in their target lesion severity score during part one. Patients were randomized to one of two groups: twice-daily calcipotriene ointment on weekdays plus twice-daily clobetasol propionate foam or placebo on weekends. Treatment groups were compared using intent-to-treat analysis. After six months of treatment, the combination therapy group showed a consistent trend toward longer maintenance of remission compared to the monotherapy group . Although the data were not found to be statistically significant, this same trend continued throughout all study assessments. The data led the authors to suggest that there might be a positive effect associated with using clobetasol propionate foam and calcipotriene ointment in pulse therapy. Given the consistency of these trends, it is probable that the results would have been statistically significant if a greater number of subjects were enrolled in the study. The above results strongly suggest that there is an advantage to using foam vehicles for drug delivery in combination sequential therapy. Once again, the foam vehicle is absorbed so quickly that calcipotriene can be applied soon thereafter without concern for dilution and incompatibility with other med ications. TOPICAL SEQUENTIAL THERAPY POSSIBILITIES BEYOND CALCIPOTRIENE The idea of sequential therapy can be applied to the combined use of any topical agents with ‘‘rabbit’’ (quick fix) characteristics and ‘‘turtle’’ (safe long- term) characteristics. For example, once-daily tazarotene (Tazorac 1 )0.1% Topical Sequential Therapy of Psoriasis 169 gel, used in combination with mometasone furoate (Elocon 1 )0.1%cream, was recently shown in clinical trials to be more efficacious than twice-daily treatment with either agent alone (26,27). These two medications appear to work synergistically and could possibly be used in a sequential mode. The more traditional topical agents such as tar or anthralin might also be more effective in combination with topical steroids in a sequential therapy scheme. The possibilities with respect to topical sequential therapy in the treatment of psoriasis are limited only by the skill and creativity of the der- matologist. Development of sequential therapy schemes using new agents such a s combined calcipotriol and betamethasone dipropionate (Dovobet 1 ) promises increased rate of initial improvement relative to calcipotriene alone and minimized long-term side effects if used in a sequential scheme, and may make the treatment of this chronic disease more convenient. REFERENCES 1. Kragballe K, Gjertsen BT, de Hoop D, et al. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991; 337:193–196. 2. Cunliffe WJ, Berth-Jones J, Claudy A, et al. Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris. J Am Acad Dermatol 1992; 26:736–743. 3. Berth-Jones J, Chu AC, Dodd WAH, et al. A multi-centre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis. Br J Dermatol 1992; 127:266–271. 4. Ellis JP, Griffiths WAD, Klaber MR. Long-term treatment of chronic plaque psoriasis with calcipotriol ointment in patients unresponsive to short-contact dithranol. Eur J Clin Res 1995; 7:247–257. 5. Ramsay CA, Berth-Jones J, Brundin G, et al. Long-term use of topical calcipotriol in chronic plaque psoriasis. Dermatology 1994; 189:260–264. 6. Bruce S, Epinette W, Funicella T, Ison A, Johns EL, Loss R. Comparative study of calcipotriene (MC903) ointment and fluocinonide ointment in the treatment of psoriasis. J Am Acad Dermatol 1994; 31:755–799. 7. In the files at Westwood-Squibb Pharmaceutical Corporation. 8. Mason J, Mason AR, Cork MJ. Topical preparations for the treatment of psoriasis: a systematic review. Br J Dermatol 2002; 146:351–364. 9. Bruner CR, Feldman SR, Ventrapragada M, Fleischer AB. A systematic review of adverse effects associated with topical treatments for psoriasis. Dermatol Online J 2003; 9:2. 10. Lebwohl M, Siskin SB, Epinette W, et al. A multicenter trial of calcipotriene ointment with halobetasol ointment compared with either agent alone for the treatment of psoriasis. J Am Acad Dermatol 1996; 35:268–269. 11. Lamba S, Lebwohl M. Combination therapy with vitamin D analogues. Br J Dermatol 2001; 144:27–32. 12. Lebwohl M. Topical application of calcipotriene and corticosteroids: combination regimens. J Am Acad Dermatol 1997; 37(3 Pt 2):S55–S58. 170 Koo and Colaco 13. Kowalzik L. Clinical experience with topical calcitriol (1,25 dihydroxyvitamin D 3 ) in psoriasis. Br J Dermatol 2001; 144:21–25. 14. Katz HI, Hien NT, Prawer SE, et al. Betamethasone dipropionate in optimized vehicle: intermittent pulse dosing for extended maintenance treatment of psoriasis. Arch Dermatol 1987; 123:1308–1311. 15. Lebwohl M, Siskin SB, Epinette W, et al. Calcipotriene ointment and halobetasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement. J Am Acad Dermatol 1998; 39:447–450. 16. Kragballe K. Vitamin D3 analogues. Dermatol Clin 1995; 13:835–839. 17. Patel B, Siskin S, Krazmien R, et al. Compatibility of calcipotriene with other topical medications. J Am Acad Dermatol 1998; 38:1010–1011. 18. Lenn J, Tanojo H, Huang X. Anatomical region variations on the in vitro skin permeation of clobetasol propionate formulations. Presented at 62nd annual meeting of the Academy of Dermatology, Washington, D.C., 2004. 19. Huang X, Tanojo H, Lenn J, Deng CH, Krochmal L. A novel foam vehicle for delivery of topical corticosteroids. J Am Acad Dermatol 2005; 53(1 suppl 1): S26–S38. 20. Lenn J, Madlambayan L, Huang X, Tanojo H. Comparison of clobetasol propionate skin permeation and drug distribution in vitro from various topical drug delivery vehicles (foam, lotion, and wash-off shampoo). Presented at summer meeting of the American Academy of Dermatology, New York, NY, 2004–2005. 21. Deng H, Tanojo H, Lenn J, Cuesico C, Huang X. Foam as a novel vehicle in topical therapy. Presented at 62nd annual meeting of the American Academy of Dermatology, Washington, D.C., 2004. 22. Huang X, Tanojo H, Lenn J, Cuesico C, Deng H. Impact of vehicle on clobetasol propionate skin permeation and drug distribution in vitro. Presented at 62nd annual meeting of the American Academy of Dermatology, Washington, D.C., 2004. 23. Blum R, Stern D, Lebwohl M, Bandow G, Koo J, Cheplo K. A multi-center study of calcipotriene 0.005% ointment and clobetasol propionate 0.05% foam in the sequential treatment of localized plaque-type psoriasis. Presented at summer meeting of the American Academy of Dermatology, New York, NY, 2004. 24. Koo J, Blum R, Lebwohl M, Stern D, Bandow G, Cheplo K. A 2-part, multi-center study of calcipotriene ointment, 0.005% and clobetasol propionate foam 0.05% in the sequential treatment of localized plaque-type psoriasis: long-term outcomes. Presented at 63rd annual meeting of the American Academy of Dermatology, New Orleans, LA., 2005. 25. Franz T, Lehman P, Spellman M. Calcipotriene stability in the presence of steroid foam. Presented at 60th annual meeting of the American Academy of Dermatology, New Orleans, LA., 2002. 26. Green L, Sadoff W. A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid-high-potency corticosteroid, in patients with stable plaque psoriasis. J Cutan Med Surg 2002; 6(2):95–102. 27. Koo JY, Martin 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. Int J Dermatol 2001; 40(3):210–212. Topical Sequential Therapy of Psoriasis 171 14 New Developments in Topical Psoriasis Therapy Chai Sue Lee Department of Dermatology, University of California Davis Medical Center, Sacramento, California, U.S.A. John Y. M. Koo and Shanthi M. Colaco Department of Dermatology, Psoriasis and Skin Treatment Center, University of California San Francisco Medical Center, San Francisco, California, U.S.A. INTRODUCTION There have not been many new developments in topical therapies for psoriasis in the past few years. One of the few new topical agents that was recently approved by the United States Food and Drug Administration is a fixed- dose formulation of 0.064% betamethasone dipropionate and 0.005% calcipotriene ointment (Taclonex). This fixed-dose combination therapy is discussed separately in Chapter 7. In this chapter, we will discuss other new topical psoriatic therapies including a new spray formulation of clobetasol propionate 0.05% (Clobex Spray) and two other formulations of clobetasol propionate 0.05%, a shampoo (Clobex Shampoo), and lotion (Clobex Lotion) as well as Hydrogel patch. 173 [...]... Dermatol 2003; 120(4):6 27 632 Palmoplantar Psoriasis 193 6 Volden G Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing Acta Derm Venereol 1992; 72 (1): 69 71 7 Thiers BH The use of topical calcipotriene/calcipotriol in conditions other than plaque-type psoriasis J Am Acad Dermatol 19 97; 37( 3 Pt 2):S69–S71; 5 8 Duweb GA, Abuzariba O, Rahim M, al... treatment of psoriasis Arch Dermatol 1981; 1 17: 770 77 4 13 Fisher LB, Maibach HI Physical occlusion controlling epidermal mitosis J Invest Dermatol 1 972 ; 59:106–108 14 Friedman SJ Management of psoriasis vulgaris with a hydrocolloid occlusive dressing Arch Dermatol 19 87; 123:1046–1052 182 Lee et al 15 Zaghloul SS, Goodfield JJ Objective assessment of compliance with psoriasis treatment Arch Dermatol 2004;... 15(2): 47 51 15 Davis MD, McEvoy MT, el Azhary RA Topical psoralen–ultraviolet A therapy for palmoplantar dermatoses: experience with 35 consecutive patients Mayo Clin Proc 1998; 73 (5):4 07 411 16 Grundmann-Kollmann M, Behrens S, Peter RU, Kerscher M Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy Photodermatol Photoimmunol Photomed 1999; 15(2): 87 89... 1999; 15(2): 87 89 17 Hawk JL, Grice PL The efficacy of localized PUVA therapy for chronic hand and foot dermatoses Clin Exp Dermatol 1994; 19(6): 479 –482 18 Layton AM, Sheehan-Dare R, Cunliffe WJ A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis Br J Dermatol 1991; 124(6):581–584 19 Schiener R, Gottlober P, Muller B, et al PUVA-gel vs PUVA-bath therapy for... but could be of potential therapeutic benefit PHOTOTHERAPY Ultraviolet B Therapy Ultraviolet B (UVB) phototherapy has been a standard therapy for psoriasis for decades More recently, narrowband UVB (NB-UVB) treatment has come into common usage Like other treatments for palmoplantar psoriasis, however, data on its effectiveness are limited In one open-label prospective study of of NB-UVB therapy, 9 of... experience rather than evidence-based approaches REFERENCES 1 Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice J Am Acad Dermatol 2003; 49(2): 271 – 275 2 Kumar B, Saraswat A, Kaur I Palmoplantar lesions in psoriasis: a study of 3065 patients... convenient alternative to current methods of occlusion in psoriasis and may significantly enhance topical therapy of psoriasis New Developments in Topical Psoriasis Therapy 181 CONCLUSIONS Psoriasis is a chronic disease and therefore requires long-term treatment However, only 60% of patients are compliant with their therapy (15) There are several reasons why psoriasis patients are not compliant with their treatments... Most studies of therapy for psoriasis have been concentrated on the most common form of the disease, chronic plaque disease Studies of topical therapy, phototherapy, and systemic therapy for palmoplantar psoriasis are often performed after the primary investigations of plaque psoriasis These studies may not be well-designed, placebo-controlled trials and are fraught with other potential confounding factors... small series in the literature (7) There have, however, been no reported placebo-controlled trials In one randomized trial, calcipotriol used twice weekly under occlusion was compared to twice a day application in a six-week period (8) In this small study, occlusive therapy was equivalent to twice-daily treatment (26% and 25% improvement in clinical score, respectively), potentially allowing for a tolerable... severe plaque psoriasis affecting up to 20% body surface area in 18-year old patients or older The total dosage should not exceed 50 g/wk Two multicenter, randomized, double-blind, vehicle-controlled phase III studies have shown consistent rapid reduction in overall disease severity with twice daily clobetasol propionate spray in patients aged 18 years and older with moderate to severe plaque psoriasis . calcipotriol (MC 903) ointment and betamethasone 1 7- valerate ointment in patients with psoriasis vulgaris. J Am Acad Dermatol 1992; 26 :73 6 74 3. 3. Berth-Jones J, Chu AC, Dodd WAH, et al. A multi-centre,. parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis. Br J Dermatol 1992; 1 27: 266– 271 . 4. Ellis JP, Griffiths WAD, Klaber MR. Long-term. chronic plaque psoriasis with calcipotriol ointment in patients unresponsive to short-contact dithranol. Eur J Clin Res 1995; 7: 2 47 2 57. 5. Ramsay CA, Berth-Jones J, Brundin G, et al. Long-term use

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