Dermatology Online Journal

Efficacy of high-concentration tacalcitol ointment in psoriasis vulgaris after changing from other high-concentration vitamin D3 ointments
Masatoshi Abe MD, Tomoko Syuto MD, Hirohisa Ishibuchi MD, Yoko Sogabe MD, Yoko Yokoyama MD, Osamu Ishikawa MD
Dermatology Online Journal 14 (2): 2

Department of Dermatology, Gunma University Graduate School of Medicine, Japan. masaabe@med.gunma-u.ac.jp

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Abstract

Three high-concentration vitamin D3 ointments are currently available in Japan for the treatment of psoriasis. The aim of the present study is to investigate the efficacy of high-concentration tacalcitol in patients with psoriasis vulgaris who have already been treated with another high-concentration vitamin D3 ointment, calcipotriol or maxacalcitol. The psoriasis area and severity index score was improved in more than half the patients after changing to the tacalcitol ointment. Many patients treated with maxacalcitol once a day achieved greater clinical improvement by changing to high-concentration tacalcitol. In contrast, some patients who had responded to a high-concentration tacalcitol ointment showed exacerbation after changing to maxacalcitol once a day. Interviews with 50 patients (including the 34 patients enrolled in the present study) indicated that high-concentration tacalcitol ointment was an acceptable therapy in terms of the number of daily applications and drug cost. The results of this clinical study suggest that high-concentration tacalcitol ointment meets the preference of many patients who wish to use an ointment once a day.

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Tacalcitol ointment is the first active vitamin D3 analog ointment approved for clinical use in Japan [1, 2, 3, 4], and recently a high-concentration tacalcitol ointment has also been released. The new tacalcitol ointment contains 20 μg/mg of tacalcitol, ten times more than conventional tacalcitol ointment (2 μg/mg). Other active vitamin D3 analogs have also been developed as high-concentration ointments [4]. These ointments are approved for twice daily use. The number of daily applications and the cost of drug are important factors affecting the acceptability of treatments.

The new high-concentration tacalcitol ointment is approved for once daily application, and this advantage may contribute to patients' quality of life and compliance with treatment. Our preliminary survey revealed that 83 percent of patients preferred once a day application to twice daily use (data not shown). The high-concentration tacalcitol ointment is relatively expensive as compared with the other vitamin D3 ointments based on the price per gram, however, the high-concentration tacalcitol ointment may be cost effective considering it is applied only once a day. In the present study, we investigated the efficacy of high-concentration tacalcitol in patients with psoriasis vulgaris who had been treated with other high-concentration vitamin D3 ointments, calcipotriol or maxacalcitol. We also interviewed patients to determine their preference in choosing vitamin D3 ointments.

Methods

After obtaining informed consent, 34 patients with psoriasis vulgaris treated at our department were enrolled in this study. The patients had been treated with calcipotriol (n=16) or maxacalcitol (n=18), achieved some improvement, but the improvement reached a plateau. The psoriasis area and severity index (PASI) scores of the patients were constant for more than 4 weeks. Patients were then switched to the high-concentration tacalcitol ointment (Fig. 1). The last PASI score of calcipotriol or maxacalcitol therapy was compared with the PASI score after 4 weeks of high-concentration tacalcitol therapy. We also conducted a similar study on 6 patients who had been treated with high-concentration tacalcitol and then changed to maxacalcitol. Stable concomitant therapy was allowed, but patients concomitant therapies were not changed during the study period. PASI scores of each patient were graded as follows:

Percent change of PASI score = (PASI score of the latter therapy / PASI score of the former therapy) × 100 (%)

• Improved: Percent change of PASI score＜70 percent
• No changed: 70 percent≦percent change of PASI score≦130 percent
• Deteriorated: Percent change of PASI score＞130 percent

To investigate the factors influencing patients' attitude in their choice of drug, we conducted interviews regarding their preference of vitamin D3 ointments. To obtain a larger sample size, 16 psoriasis patients were further included to the original patient group.

Figure 1	Figure 2
Figure 1. Study design of the present investigation Figure 2. A patient who "improved" by changing from calcipotriol to high-concentration tacalcitol (patient #6). Left: pre-treatment Center: before changing from calcipotriol Right: after changing to high-concentration tacalcitol

Results

Calcipotriol changed to high-concentration tacalcitol

Eleven out of 16 patients were "improved" after changing to high-concentration tacalcitol, 5 patients showed "no change," and no patient "deteriorated" (see Table 1). Four patients had noted skin irritation with calcipotriol. In these patients, however, this adverse symptom abated after starting treatment with high-concentration tacalcitol. Of 6 patients who had applied calcipotriol once a day, 5 patients obtained improvement after changing to high-concentration tacalcitol. A representative patient is shown in Fig. 2 (patient #6).

Maxacalcitol changed to high-concentration tacalcitol

Seven out of 18 patients were "improved" after changing to high-concentration tacalcitol, 9 patients had "no change", and 2 patients "deteriorated" (see Table 2). Two "deteriorated" patients had high serum calcium concentrations during maxacalcitol treatment, but normal serum calcium concentrations were maintained throughout the period of high-concentration tacalcitol treatment. Of 9 patients who had used maxacalcitol once a day, 5 patients improved by changing to high-concentration tacalcitol. A representative case is shown in Fig. 3 (patient #4).

High-concentration tacalcitol was changed to maxacalcitol

Of 10 patient whose symptoms improved after changing from maxacalcitol to high-concentration tacalcitol, 6 patients changed to the treatment with maxacalcitol once a day in order to evaluate the difference in efficacies of once a day use of maxacalcitol or high-concentration tacalcitol. One patient "improved," 2 patients showed "no change," and 3 patients "deteriorated" in PASI score (see Table 3).

Figure 3	Figure 4
Figure 3. A patient who "improved" by changing from maxacalcitol to high-concentration tacalcitol (patient #4). Left: pre-treatment. Center: before changing from maxacalcitol. Right: after changing to high-concentration tacalcitol. Figure 4. Results of interview with patients (n=50). a) the number of applications, b) drug cost, c) final evaluation by patients. The question are as follows: a) Which do you think is more convenient for you, once a day application or a twice a day application? b) The once a day application is two times as expensive as twice a day application, but you need only the half quantity for the once a day use as compared to twice a day use. Namely, the cost per day is same. In this situation, which is better for you? c) Which ointment do you want to continue, the former one (calcipotriol, maxacalcitol) or the current one (high-concentration tacalcitol)?

Number of applications

For the first question, "Which do you think is more convenient for you, once a day application or a twice a day application?" 29 patients (58%) answered "once a day application is better," 12 patients (24%) responded "twice a day application is better," and the remaining 9 patients (18%) reported "I can't decide" (Fig. 4a).

Drug cost

For the question, "Once a day application is two times as expensive as twice a day application, but you need only half the quantity for once a day use as compared to twice a day use. Namely, the cost per day is same. In this situation, which is better for you?" 27 patients (54%) answered, "both are acceptable," 14 patients (28%) said "twice a day use is better," and 9 patients (18%) said "Once a day use is better" (Figure 4b).

Final evaluation by patients

For the question "Which ointment do you want to continue, the former one (calcipotriol or maxacalcitol) or the current one (high-concentration tacalcitol)?" 21 patients (42%) answered "the current ointment," 16 patients (32%) "the former ointment," and 13 patients (26%) "both are acceptable" (Fig. 4c).

Discussion

Active vitamin D3 ointments are a first line therapy for psoriasis vulgaris [1, 2, 3, 4]. Three kinds of high-concentration vitamin D3 ointments are currently available in Japan. Since all three drugs have good efficacy, there may be a tendency to think the three ointments yield the same consequence. However, these ointments may have different properties. For example, their efficacies differ for various skin diseases other than psoriasis vulgaris [5]. Also the potential adverse effects such as skin irritation and elevated serum calcium are different among them [6, 7, 8]. When different high-concentration ointments are applied to different sides (right and left) of the body in the same patient, the clinical effects are often different (data not shown). Therefore, establishment of the appropriate rationale to choose among vitamin D3 ointments may provide tactics to use these drugs more effectively.

When choosing an ointment, patients' preferences are also of great importance. In the current study, patients tend to prefer the ointment that requires less frequent application. In this respect, the application of high-concentration tacalcitol ointment once a day application may be most convenient for patients [9, 10].

In the present study, many patients achieved greater improvement by changing to high-concentration tacalcitol. This suggests that there is difference in the potency among vitamin D3 ointments. In patients for whom the ointment was changed from calcipotriol to high-concentration tacalcitol, two-thirds of the patients were "improved" in PASI score and no patient was "deteriorated." In patients in whom the ointment was changed from maxacalcitol to high-concentration tacalcitol, many patients showed "no change," but only a few patients were "improved." Interestingly, many of patients treated with maxacalcitol once a day improved by changing their ointment to high-concentration tacalcitol once a day. In addition, many patients who had responded well to high-concentration tacalcitol deteriorated after changing their treatment to once a day use of calcipotriol. These facts may suggest that high-concentration tacalcitol is most effective in treating psoriasis vulgaris when used once a day. Some studies comparing calcipotriol ointment and maxacalcitol ointment reported that there were no statistical differences in the efficacy of these ointments, however, maxacalcitol ointment was more efficient [11]. In the study comparing maxacalcitol ointment with high-concentration tacalcitol ointment, maxacalcitol ointment used twice daily was more effective than high-concentration tacalcitol ointment used once daily, but high-concentration tacalcitol ointment was superior when both drugs were used once daily [12]. That observation agrees with our results.

The interviews revealed that patients tend to prefer once a day application over twice a day. The price per package (10 g) of high-concentration tacalcitol is twice as expensive as that of maxacalcitol or calcipotriol. However, it can be used once a day and therefore, the cost per day is almost the same in the three ointments. The higher per gram cost of high-concentration tacalcitol seems to be accepted by patients.

In conclusion, many patients with psoriasis vulgaris who were already treated with calcipotriol or maxacalcitol could achieve further improvement by changing to high-concentration tacalcitol. Also, interviews with patients indicated that high-concentration tacalcitol was an acceptable therapy in terms of the number of application and drug cost. High-concentration tacalcitol ointment meets the preference of patients, and may be a good option for patients who desire to use an ointment once a day.

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