Mild-to-Moderate Psoriasis - part 4 doc

54. Mortensen L, Kragballe K, Wegmann E, et al. Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism: a randomized, double-blind, placebo-controlled study. Acta Derm Venereol 1993; 73:300–304. 55. Berth-Jones J, Bourke JF, Iqbal SJ, et al. Urine calcium excretion during treat- ment of psoriasis with topical calcipotriol. Br J Dermatol 1993; 129:411–414. 56. Gumowski-Sunek D, Rizzoli R, Saurat J-H. Effects of topical calcipotriol on cal- cium metabolism in psoriatic patients: comparison with oral calcitriol. Dermato- logica 1991; 183:275–279. 57. Berth-Jones J, Bourke JF, Elouzi H, et al. Immediate and long term effects of topical calcipotriol on calcium homeostasis during treatment of psoriasis. Br J Dermatol 1992; 127(suppl 40):17–18. 58. Saurat J-H, Gumowski-Sunek D, Rizzoli R. Topical calcipotriol and hypercal- caemia [letter]. Lancet 1991; 337:1287. 59. Gumowski-Sunek D, Rizzoli R, Saurat J-H. Calcium tolerance test in patients with extended body surface psoriasis and treated with calcipotriol. Dermatology 1992; 185(3):229–230. 60. Gawkrodger DJ. Current management of psoriasis. Audit Subcommittee of the British Association of Dermatologists. J Dermatol Treat 1997; 8:27–55. 74 Lee and Koo 7 Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy Chai Sue Lee Department of Dermatology, University of California Davis Medical Center, Sacramento, California, U.S.A. John Y. M. Koo Department of Dermatology, Psoriasis and Skin Treatment Center, University of California San Francisco Medical Center, San Francisco, California, U.S.A. Recent advances in psoriatic therapy have predominantly revolved around the development of biologics for the treatment of moderate-to-severe psori- asis and the use of targeted phototherapy. However, the majority of patients with mild to moderate disease are still managed with topical therapy (1). The two most widely prescribed topical therapies for psoriasis are corticosteroids and vitamin D 3 analogs. In a survey of 650 patients from an academic der- matology practice in the United States, 79% of patients were prescribed topical steroids (2). In Europe, the most widely prescribed topical therapy is reported to be the vitamin D 3 analog calcipotriene (calcipotriol) (3). Unfortunately, there have not been many new topical therapies for psoriasis developed in the past few years. Despite their widespread use and demonstrated efficacy, the chronic use of topical corticosteroids or vitamin D 3 analogs is associated with safety and efficacy concerns. Potential side effects from topical corticosteroids 75 include cutaneous atrophy, striae, and, suppression of the hypothalamic- pituitary-adrenal axis. The efficacy of long-term topical corticosteroid therapy may be compromised by tachyphylaxis (4). Although this issue is unresolved at this time, potential explanations include inability of topical corticosteroid monotherapy to completely clear lesions, exacerbation unrelated to the topi- cal steroid, and impaired compliance. The most common side effect of topical vitamin D 3 analogs is irritation of the lesions and/or the surrounding skin (5) In addition, topical calcipotriene in excess of 100 to 200 g/wk has been asso- ciated with hypercalcemia (6). COMBINATION CORTICOSTEROID/CALCIPOTRIENE THERAPY To maximize the benefits of topical therapy, topical corticosteroids are often administered in combination with a second topical agent such as calcipo- triene. Potential benefits of combination therapy include improved disease control and decreased adverse events. Benefits of combination therapy are derived from differing mechanisms of action and less overall exposure to the individual components. For example, the combination of a topical cor- ticosteroid plus topical calcipotriene is reported to be particularly effective at clearing psoriatic lesions without significant cutaneous irritation from the latter or skin atrophy from the former. In fact, combination topical ther- apy with calcipotriene in the morning and corticosteroid in the evening has been demonstrated to be more effective than either agent applied b.i.d. as monotherapy (7–9). Unfortunately, combination therapy has its own pit- falls. For example, stacking or combining different agents may inactivate one or both products or require complicated dosing schedules. These issues may negatively impact compliance because of lack of anticipated efficacy or difficulties with compliance. A fixed-dose corticosteroid/calcipotriene ointment has been available in Europe and Canada (Dovobet 1 , Daivobet 1 ) for a few years and recently was approved by the U.S. Food and Drug Administration (Taclonex 1 ). It is one of the few new topical agents to become available. The product is a fixed-dose formulation of 0.064% betamethasone dipropionate (equivalent to 0.5 mcg of betamethasone dipropionate), a class II high-potency (U.S.A. classification) synthetic fluorinated corticosteroid, and 0.005% calcipotriene ointment (equivalent to 50 mcg of calcipotriene), a syn- thetic 1,24-dihydroxyvitamin D 3 analog. A stable formulation of the two active agents was achieved by mixing them in a novel anhydrous vehicle. The atro- phogenic potential and bioavailability of betamethasone dipropionate in the two-drug combination appears equal to that in betamethasone dipropionate (Diprosone 1 ) ointment (10,11). Moreover, the biologic activity of calcipo- triene in the combination is the same as it is in calcipotriene (Dovonex 1 , Daivonex 1 ) ointment (12). 76 Lee and Koo CLINICAL TRIALS AND ANALYSES OF FIXED-COMBINATION FORMULATION OF BETAMETHASONE DIPROPIONATE/CALCIPOTRIENE Topical fixed-dose betamethasone dipropionate/calcipotriene has been evalu- ated in seven large international trials involving more than 7000 patients with psoriasis involving 10% to 30% of total body surface area. In all trials, psoriasis severity was assessed at baseline, during, and at the end of treatment using the Psoriasis Area and Severity Index (PASI). All seven trials demonstrated consis- tent reduction in PASI of approximately 40% after one week and 70% after four weeks of betamethasone diprop ionate/calcipotriene thera py (13). THE FIXED-DOSE COMBINATION IS MORE EFFECTIVE THAN STEROID OR CALCIPOTRIENE MONOTHERAPY In a four-week, double-blind study, 1106 patients were randomized into one of three groups: (i) b.i.d. betamethasone dipropionate/calcipotriene ointment, (ii) b.i.d. betamethasone dipropionate ointment, and (iii) b.i.d. calcipotriene ointment (13). The four-week, double-blind phase of the trial was followed by an open-label phase in which patients were treated with calcipotriene oint- ment b.i.d. for four weeks. The baseline PASI scores were 10.8, 10.5, and 10.9 for the combination, betamethasone dipropionate, and calcipotriene groups, respectively. The mean percentage changes in PASI at one week were 47.4%, 39.8%, and 31.0% for the combination, betamethasone dipropionate, and cal- cipotriene groups, respectively; mean percentage changes in PASI at the end of the four-week, double-blind phase were 74.4%, 61.3%, and 55.3% for the combination, betamethasone dipropionate, and calcipotriene groups, respec- tively. Overall, the mean reduction in PASI observed with the combination was significantly greater (p < 0.001) than that elicited by the individual components. The percentages of patients with at least 75% improvement in their PASI at the end of the double-blind phase were 68.0%, 46.6%, and 38.9% for the combination, betamethasone dipropionate, and calcipotriene groups, respectively. The percentages of patients with lesional/perilesional adverse reactions during the four-week, double-blind phase (i.e., after only four weeks of therapy) were 8.1%, 4.7%, and 12.0% for the combination, betamethasone dipropionate, and calcipotriene groups, respectively. THE FIXED-DOSE COMBINATION B.I.D. ACHIEVES GREATER PASI REDUCTION WITHIN ONE WEEK VS. STEROID MONOTHERAPY In a double-blind, four-week study, 1040 patients with psoriasis (mean PASI on inclusion: 10.8) were randomized into one offour groups: (i) b .i.d. betametha- sone dipropionate/calcipotriene in the n ew vehicle, (ii) b.i.d. betamethasone Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy 77 dipropionate in the new vehicle, (iii) b.i.d. calcipotriene in the new vehicle, and (iv) b.i.d. with the new vehicle alone (14). The mean decrease in PASI at one week for the combination group was 48.1%, which already was statistically signifi- cantly greater ( p < 0.001) than the decreases observed in the betamethasone dipropionate, calcipotriene, and vehicle groups (41.4%, 28.4%, and 21.5%, res- pectively). The mean decreases in PASI after four weeks were 73.2%, 63.1%, 48.8%, and 28.8%, respectively for the combination, betamethasone dipropio- nate, calcipotriene, and vehicle groups with the decrease in patients receiving the combination significantly greater ( p < 0.001) than inthe comparator groups. Lesional/perilesional adverse events were reported in 9.9%, 8.6%, 17.2%, and 15.7% of patients, respectively for the combination, betamethasone dipropio- nate, calcipotriene, and vehicle groups. There were significantly more adverse events in the calcipotriene-only group than in the other groups ( p ¼ 0.023). Both of the above studies show the combination to be well tolerated, more effective, and with a more rapid onset of action than either active agent used alone. ONCE-DAILY FIXED-DOSE COMBINATION IS SAFE AND EFFECTIVE In another double-blind, four-week study, 1603 patients were randomized into one of four groups: (i) once-daily betamethasone dipropionate/calcipo- triene ointment, (ii) once-daily betamethasone dipropionate ointment in the same anhydrous vehicle, (iii) once-daily calcipotriene ointment in the same anhydrous vehicle, and (iv) the vehicle alone (15). Baseline PASI scores were 9.9, 9.8, 10.4, and 9.5 for the combination, betamethasone dipropionate, calcipotriene, and vehicle-only groups, respectively. After one week of treat- ment, the mean percentage changes in PASI were 39.2%, 33.3%, 23.4%, and 18.1% for the combination, betamethasone dipropionate, calcipotriene, and vehicle-only groups, respectively (Fig. 1). The mean difference in PASI reduction was significantly greater (p < 0.001) for the combination group than for the comparator groups. The mean percentage changes in PASI after four weeks were 71.3%, 57.2%, 46.1%, and 22.7% for the combination, betametha- sone dipropionate, calcipotriene, and vehicle-only groups, respectively (15). The percentages of patients having controlled disease (classified as having ‘‘absence of disease’’ or ‘‘very mild disease’’) as determined by using the Inves- tigators’ Global Assessment (IGA) were 56.3%, 37.0%, 22.3%, and 10.2% for the combination, betamethasone dipropionate, calcipotriene, and vehicle- only groups, respectively (Fig. 2). The odds ratio of having controlled disease was significantly greater (p < 0.001) in patients treated with the combination. The percentages of patients with lesional/perilesional adverse reactions were 6.0%, 4.9%, 11.4%, and 13.6% for the combination, betamethasone dipropio- nate, calcipotriene, and vehicle-only groups, respectively. The rates of adverse reactions were similar between the betamethasone dipropionate/calcipotriene combination and betamethasone dipropionate ointment, while calcipotriene 78 Lee and Koo ointment and even the vehicle alone had significantly higher rates of adverse reactions compared with the betamethasone dipropionate/calcipotriene com- bination. Thus, this study confirmed that once-daily use of the fixed-dose combination could produce rapid and sustained clearance of psoriatic lesions. In addition, more patients treated with the formulation achieved disease con- trol than those randomized to monotherapy. Figure 1 Once-daily fixed-dose combination therapy versus monotherapy. Once- daily fixed-dose combination therapy achieves greater and more rapid improvement in psoriasis area and severity index scores than monotherapy. Figure 2 Once-daily fixed-dose combination therapy versus monotherapy. More patients achieve disease control with fixed-dose combination therapy. Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy 79 ONCE-DAILY FIXED-DOSE COMBINATION IS AS SAFE AND EFFECTIVE AS B.I.D. THERAPY A four-week study addressed the efficacy of once-daily versus b.i.d. therapy (16). In this study, 828 patients were randomized to four groups: (i) once- daily betamethasone dipropionate/calcipotriene ointment and once-daily vehicle, (ii) b.i.d. betamethasone dipropionate/calcipotriene ointment, (iii) b.i.d. calcipotriene ointment, and (iv) b.i.d. vehicle. Mean PASI at entry was 9.9, 10.6, 10.8, and 10.4 for the q.d. combination, b.i.d. combination, b.i.d. calcipotriene, and b.i.d. vehicle groups, respectively. After one week, the average reductions in PASI were 45.5%, 47.6%, 33.6%, and 20.0% for the q.d. combination , b.i.d. combination, b.i.d. calcipotriene, and b.i.d. vehicle groups, respectively. The differences in PASI from baseline in the patients treated with either b.i.d. or q.d. combination were significantly greater (p < 0.001) than the calcipotriene and vehicle groups. There was no statisti- cal difference in PASI between the q.d. and b.i.d. combination group (Fig. 3). After four weeks, the mean reductions in PASI were 68.6%, 73.8%, 58.8% , and 26.6% for the q.d. combination, b.i.d. combination, b.i.d. calcipotri- ene, and b.i.d. vehicle groups, respectively. Similar to results observed after one week, the reduction in PASI elicited by either combination regimen was significantly greater (p < 0.001) than that of the other treat ments. Similar efficacy is seen with once-daily versus b.i.d. treatment with betamethasone dipropionate/calcipotriene ointment. The pe rcentages of patients with at least 75% impr ovement were 73.5%, 63.3%, 50.7%, and 9.2% for the b.i.d. combination, q.d. combination, b.i.d. calcipotriene, and b.i.d. vehicle groups, Figure 3 Once-daily versus twice-daily fixed-dose combination therapy. There was no statistical difference in psoriasis area and severity index between once-daily and twice-daily combination groups. 80 Lee and Koo respectively. Lesional/perilesional adverse events were reported in 10.6%, 9.9%, 19.8%, and 12.5% of patients for the b.i.d. combination, q.d. combina- tion,b.i.d.calcipotriene, andb.i.d. vehiclegroups,respectively. Theproportion of patients who experienced adverse reactions was lower in the combined for- mulation groups than in the calcipotriene group (p < 0.01). Therefore, the efficacy of once-daily application was not shown to be different from that of b.i.d. use, and once-daily combination was shown to be more effective and better tolerated than b.i.d. calcipotriene ointment. ONCE-DAILY FIXED-DOSE THERAPY ACHIEVES HIGHER CLEARANCE AND FEWER ADVERSE EVENTS VS. MONOTHERAPY In an investigator-blinded study involving 972 patients, two different regi- mens involving betamethasone dipropionate/c alcipotriene ointment were compared with eight weeks of b.i.d. calcipotriene ointment therapy (17). In one group, betamethasone dipropionate/c alcipotriene ointment was applied daily for eight weeks; in the second group, it was applied daily for four weeks followed by four weeks of intermittent therapy (betamethasone dipropionate/calcipotriene ointment once daily on Saturday and Su nday, and calcipotriene ointment once daily on weekdays). Mean PASI at baseline was 10.3, 10.4, and 10.9 for the combination-only, combination weekend/calcipo- triene weekday, and calcipotriene-only groups, respectively. At eight weeks, the mean percentage reductions in PASI were 73.3% in the once-daily beta- methasone dipropionate/calcipotriene group, 68.2% in the weekday–weekend betamethasone dipropionate/calcipotriene group, and 64.1% in the calcipo- triene group. Significantly greater improvement (p < 0.001) was noted after eight weeks of once-daily betamethasone dipropionate/calcipotriene therapy compared with four weeks of weekday–weekend therapy, but there was a pla- teau in the effect at five weeks. Lesional/perilesional adverse events were reported in 10.9%, 11.5%, and 22.3% of patients for once-daily betamethasone dipropionate/calcipotriene group, weekday–weekend betamethasone dipro- pionate/calcipotriene group, and the calcipotriene group, resp ectively, with sig- nificantly fewer (p < 0.001) adverse events occurring in the groups receiving combination therapy compared with calcipotriene alone. ONCE-DAILY FIXED-DOSE THERAPY IS EFFECTIVE FOR PATIENTS WITH MILD , MODERATE, AND SEVERE PSORI ASIS Menter et al. (18) reported the results of a pooled analysis of six randomized, double-blind, vehicle- and/or active-controlled studies using the fixed-dose betamethasone dipropionate/calcipotriene combination in patients with mild (PASI 6), moderate (PASI 6.1– 12), and severe (PASI >12) psoriasis. Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy 81 Although the analysis was somewhat limited by use of a correlation between the IGA and imputed PASI scores and by the failure of all investigators to report both IGA and PASI scores, it demonstrated that the fixed-dose com- bination used once-daily produced consistent efficacy across all degrees of disease severi ty (Fig. 4). At the end of one, two, and four weeks, the mean percent PASI reduction from baseline with the fixed-drug combination was 38.7%, 56.7%, and 67.6%, respectively, in mild disease; 37.8%, 55.3%, and 68.1%, respectively, in moderate disease; and 41.2%, 59.5%, and 71.5%, respectively, in severe disease. Thus, the combination had a more rapid onset of action than the comparators and demonstrated efficacy in patients with a spectrum of disease severities. INVESTIGATORS AND PATIENTS’ ASSESSMENTS OF ONCE-DAILY FIXED-DOSED THERAPY AGREE In this study, the investigators randomized 501 patients with stable psoriasis to receive either the combination for four weeks followed by calcipotriene for four weeks or tacalcitol only for eight weeks (19). The mean PASI at baseline for all patients was 9.7 for the combination/calcipotriene group and 9.9 for the tacalcitol group. Treatment with the combination followed by calcipotriene was significantly more effective than tacalcitol monother- apy in terms of mean percentage PASI reduction (65.0% vs. 33.3% at week 4 and 59.0% vs. 38.4% at week 8; p < 0.001 for both). During the first four weeks, the number of patients experiencing lesional or perilesional irritation was greater in the tacalcitol group (11.8%) than in the combination/calcipo- triene group (2.9%; p < 0.001). Figure 4 Psoriasis activity and severity index reduction with once-daily fixed-dose combinationtherapyin mild, moderate, and severe psoriasis. Once-daily fixed-dose com- bination therapy produces consistent efficacy across all degrees of disease severity. 82 Lee and Koo LONG-TERM, ONCE-DAILY FIXED-DOSE THERAPY IS SAFE AND EFFECTIVE Kragballe et al. completed a study designed to investigate the efficacy and safety of three treatment regimens involving use of the fixed-dose combina- tion for up to 52 weeks (20). In this study, 634 patients were randomized to once-daily treatment with 52 weeks of the fixed-do se combination, or 52 weeks of alternating four-week periods of the combination agent and calci- potriene, or four weeks of the fixed-dose combination agent followed by 48 weeks of calcipotriene ointment. All treatments were used once-daily, inter- mittently, on an as-needed basis. Patients were instructed to use as much of their assigned experimental drug as necessary to relieve symptoms an d pro- mote clearance. The clinical response observed in the initial four-week period when all patients received the combination reflected what was seen in the short-term studies reviewed above—rapid onset of action and reliable lesion clearance. These clinical benefits were best maintained in the group using the combination agent only (Fig. 5). Importantly, there was no appar- ent loss of efficacy or perceived tachyphylaxis in the fixed-dose combination arm. About 76.9% of the patients using the fixed-dose combination as needed for 52 weeks were clear or almost clear. The group that alternated between the combination agent and c alcipotriene ointment ‘‘flip-flopped’’ back and forth between better- and lesser control with better control periods affected by the use of the combination agent. Finally, the group that mostly used calcipotrien e showed more loss of efficacy than the other two groups when they were switched from the combination agent to calcipotriene at four weeks of study. This group did least well of the three groups and Figure 5 Efficacy of once-daily fixed-dose combination therapy up to 52 weeks. Once-daily fixed-dose combination therapy produces consistent long-term efficacy. Fixed-Dose Corticosteroid/Calcipotriene Combination Therapy 83 [...]... multicenter placebo-controlled study J Am Acad Dermatol 19 94; 31(1):68– 74 Zaghloul SS, Goodfield JJ Objective assessment of compliance with psoriasis treatment Arch Dermatol 20 04; 140 (4) :40 8 41 4 Krueger G, Koo J, Lebwohl M, et al The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey Arch Dermatol 2001; 137(3):280–2 84 Guenther LC Fixed-dose combination... (0.12%) for plaque-type psoriasis J Drug Dermatol 2005; 4( 2):228–230 21 Poulin YP Tazarotene 0.01% gel in combination with mometasone furoate in plaque psoriasis: a photographic tracking study Cutis 1999; 63 :41 48 22 Kaiddbey K, Kopper SC, Sefton J, et al A pilot study to determine the effect of tazarotene 0.1% gel on steroid-induced epidermal atrophy Int J Dermatol 2001; 40 :46 8 47 1 23 Hecker D, Worsley... 48 :760–767 12 Lebwohl M, Aste E, Callen J, et al Once-daily tazarotene gel versus twice-daily floucinonide cream in the treatment of plaque psoriasis J Am Acad Dermatol 1998; 38:705–711 13 Lebwohl M Strategies to optimize efficacy, duration of remission and safety in the treatment of plaque psoriasis by using tazarotene in combination with corticosteroid J Am Acad Dermatol 2000; 43 (2 Pt 3):S43–S46 14. .. tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis Br J Dermatol 1999; 140 (suppl 54) :18–23 19 Green L, Sadoff W, The Tazarotene Plus High-Potency or Mid-Potency Steroid Study Group 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 20 Dhawan S, Blyumin... the long-term treatment of psoriasis: effects on the duration of improvement J Am Acad Dermatol 1998; 39 :44 7 45 0 Frapazz A, Thivolet J Calcipotriol in combination with PUVA: a randomized double blind placebo study in severe psoriasis Eur J Dermatol 1993; 3:351–3 54 Gossman RM, Thivolet J, Claudy A, et al A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose... required to improve psoriasis The median cumulative BB-UVB dose was 390 mJ/cm2 in the combined tazarotene and BB-UVB group, while it was approximately four times higher (i.e., 1 644 mJ/cm2) in BB-UVB monotherapy To evaluate the efficacy of topical tazarotene in combination with NB-UVB, a total of 10 patients were treated with 0.05% tazarotene once daily to one side of the body and NB-UVB five times a week... 29 30 31 32 33 34 35 36 37 103 0.005% ointment twice daily in the treatment of plaque psoriasis Clin Ther 2000; 22(10):1225–1238 Lowe NJ Optimizing therapy: tazarotene in combination with phototherapy Br J Dermatol 1999; 140 (suppl 54) :8–11 Koo JY, Lowe NJ, Lew-Kaya DA Tazarotene plus UVB phototherapy in the treatment of psoriasis J Am Acad Dermatol 2000; 43 :821–828 Behrens S, Grundmann-Kollamn M, Schiener... Schiener R, et al Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel J Am Acad Dermatol 2000; 42 (3) :49 3 49 5 Schiener R, Behrens-Williams SC, Pillekamp H, et al Calcipotriol versus tazarotene as combination therapy with narrowband ultraviolet B (311 nm): efficacy in patients with severe psoriasis Br J Dermatol 2000; 143 :1275–1278 Hecker D, Worsley J, Yueh G,... Acad Dermatol 1999; 41 (6):927–930 Tzaneva S, Seebar A, Honigsmann A A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis Br J Dermatol 2002; 147 : 748 –753 Scher RK, Stiller M, Zhu YI Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study Cutis... Corticosteroid/Calcipotriene Combination Therapy 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 89 dipropionate or calcipotriol in psoriasis vulgaris Acta Derm Venereol 2002; 82(2):131–135 Papp KA, Guenther L, Boyden B, et al Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis J Am Acad Dermatol 2003; 48 (1) :48 – 54 Kauffmann R, Bibby AJ, Bissonnette . Arch Dermatol 20 04; 140 (4) :40 8 41 4. 27. Krueger G, Koo J, Lebwohl M, et al. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. Arch. combination/calcipo- triene group (2.9%; p < 0.001). Figure 4 Psoriasis activity and severity index reduction with once-daily fixed-dose combinationtherapyin mild, moderate, and severe psoriasis. Once-daily. Calcipotriene ointment and halobe- tasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement. J Am Acad Dermatol 1998; 39 :44 7 45 0. 24. Frapazz A, Thivolet J. Calcipotriol