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Topical active vitamin D3 analogs (VD3A) are one of the most commonly used therapeutic tools for psoriasis and have strong evidence for efficacy in treating psoriasis.1 Three different topical VD3A compounds, namely tacalcitol (Bon-Alfa and Bon-Alfa high; Teijin Pharma, Tokyo, Japan), calcipotriol (Dovonex; Torii Pharmaceutical, Tokyo, Japan) and maxacalcitol (Oxarol; Maruho, Osaka, Japan), are available in Japan. The clinical effects, action mechanisms, adverse effects as well as the costs of the three reagents are considered similar based on domestic clinical trial results.2–5 The differences among the reagents are that high-concentration tacalcitol requires application once a day, while the other reagents require application twice a day. VD3A have been shown to have long-term clinical effects in various clinical studies,6–8 although a gradual decline of clinical efficacy is occasionally experienced in the treatment of chronic plaque-type psoriasis with VD3A. This “loss of effect” phenomenon is considered to be more likely to arise through deterioration of the patients’ adherence to treatment than through pharmacological tachyphylaxis.9

In this study, we assessed whether switching of one topical VD3 reagent to another reagent improves the symptoms of psoriasis. This study was conducted at Fukuoka University Hospital and 11 affiliated clinics. Patients with plaque-type psoriasis who provided informed consent were enrolled in this study. Patients using tacalcitol or maxacalcitol for more than 1 month without satisfactory results were switched to calcipotriol ointment. Patients using calcipotriol were changed to tacalcitol or maxacalcitol assigned alternately at each facility. Topical steroids in use at the time of enrollment in the study were allowed to be used continuously with the condition that the products were not changed during the observation period. Patients’ visits and examinations were scheduled at 4 and 8 weeks. The clinical effects were evaluated by the body surface area, erythema, induration, scale, itching and skin atrophy based on four grades (0, none; 1, slight; 2, moderate; 3, severe). The results were analyzed statistically by Wilcoxon rank sum test, and values of P < 0.05 were considered statistically significant. Questionnaires were anonymously taken before and after the 8-week trial. Patients were asked about the changes in their clinical symptoms, whether they had followed their doctors’ directions, whether they were pleased with changing their VD3 reagent and whether their quality of life had improved. This study was approved by the Ethical Committee of Fukuoka University and written consent were obtained from all the enrolled patients. A total of 48 patients were enrolled in this study (Table 1). Before the study, maxacalcitol, tacalcitol and calcipotriol were used in 30, 11 and seven patients, respectively. After the study, maxacalcitol, tacalcitol and calcipotriol were used in two, five and 41 patients, respectively. Topical corticosteroids were used in 38 (79%) patients. Patients were divided into two groups, namely patients switched from tacalcitol or maxacalcitol to calcipotriol (group I), and those switched from calcipotriol to others (group II). Because the number of the patients originally prescribed with calcipotriol was small, inequality in numbers were observed between two groups. The data for the skin symptoms are shown in Figure 1. The mean erythema score was significantly reduced from 2.22 before the trial to 1.59 and 1.44 after 4 and 8 weeks in group I, respectively. The mean erythema score was significantly reduced from 2.29 to 1.43 and 1.29 after 4 and 8 weeks in group II, respectively. The mean induration score was significantly reduced from 1.95 before the trial to 1.27 and 1.03 after 4 and 8 weeks in group I, respectively. The mean induration score was significantly reduced from 2.14 to 1.29 and 0.86 after 4 and 8 weeks in group II, respectively. The mean scale score was significantly reduced from 1.87 before the trial to 1.17 and 1.03 after 4 and 8 weeks in group I, respectively. The mean scale score was significantly reduced from 2.57 to 1.57 and 1.14 after 4 and 8 weeks in group II, respectively. The mean body surface area score was significantly reduced from 2.70 before the trial to 2.35 in group I and from 3.14 to 2.57 in group II after 4 weeks, and 2.06 and 2.29 after 8 weeks, respectively. The mean itching score was significantly reduced from 2.17 before the trial to 1.80 and 1.61 after 4 and 8 weeks in group I, respectively. The mean itching score was significantly reduced from 2.29 to 1.71 and 1.33 after 4 and 8 weeks in group II, respectively. The mean atrophy score was not changed from 1.22 before the trial to 1.22 and 1.17 after 4 and 8 weeks in group I, respectively. The mean atrophy score was not changed from 1.00 before and after 4 and 8 weeks in group II. There were no significant differences between the mean scores of the two groups in all items examined except the scale score at the beginning of the trial (0 weeks). The questionnaire results were as follows. Before the trial, 37% (17/46) of patients answered that they are reluctant to use topical agents. Also, 37% (17/46) of patients answered that they are not following the physicians’ instruction for the usage of topical reagents. After 8 weeks, 58% of the patients answered that their skin symptoms were improved; 33% (13/40) answered they had improved their application habits and adhered to the rules provided by their physicians and 58% answered that changing VD3 reagents was profitable for them. Topical therapy is the most essential therapeutic modality for mild to moderate psoriasis. Topical therapy is also useful in patients who are reluctant to receive systemic therapy because of various side-effects such as hypertension, immunosuppression or liver damage.10 Topical application is easy, only affects the lesions, works quickly and is safe with very few serious side-effects. However, dermatological clinics occasionally encounter difficulty in treating patients with a long history of psoriasis using topical reagents. Some patients seem to become tired of the repetition of the topical treatment. Indeed, topical treatment has been shown to be one of the most negative aspects of psoriasis.11

Table 1. Table 1. Profiles of the patients enrolled in the study
GroupIII
  1. *P < 0.05.

No. of patients41 (28 men, 13 women)7 (6 men, 1 woman)
Age, years (range)Mean 62.3 (35–84)Mean 64.3 (44–84)
Disease duration, years
  <100
  1–5103
  6–1031
  11–20152
  >20111
  Unknown20
Skin score* (mean ± standard error)6.00 ± 0.837.00 ± 0.53
ComorbiditiesYes, 20Yes, 3
Diabetes mellitus, 5; hypertension, 6; hyperlipidemia, 2; others, 15.Diabetes mellitus, 1; others, 3
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Figure 1.  Objective measures of psoriasis after switching to a new vitamin D3 topical reagent. *P < 0.05 and **0.01, respectively, between each observation day (4 and 8 weeks) and 0 weeks of each group. Comparison between the groups were all insignificant except the scale score at 0 weeks. BSA, body surface area; n.s., not significant.

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Exacerbation of psoriasis, even when it is merely caused by neglecting the daily topical application, allows physicians to choose more potent and expensive modalities such as cyclosporin or anti-tumor necrosis factor-α antibodies, which may be associated with more difficulty in controlling adverse events. Therefore, raising patients’ motivation as well as their actual topical application habits is important.

Topical VD3 is an excellent therapeutic tool with sufficient efficacy evidence and safety profile.1,6–8 Although monotherapy is relatively mild and slow, combinations with topical corticosteroids have been shown to bring about better results than each single application.12 VD3 has also been shown to be useful for reducing the amounts of corticosteroids required.13 In Japan, VD3 is available in three different forms, namely tacalcitol, calcipotriol and maxacalcitol. These three reagents have similar efficacies and side-effects.2–4 We planned to switch a VD3 reagent to an analogous VD3 reagent in patients who had suffered from unsuccessful clinical results with long-term topical application of the same VD3 reagent. Our study showed that switching one VD3 reagent to another VD3 reagent could improve the objective scores of the psoriasis symptoms. It was surprising that switching to calcipotriol or other reagents improved the eruption in a similar way. This could possibly be explained by patients’ improved adherence based on the very similar results of the clinical trials. When switching reagents, the patients may anticipate the effects of a new drug. In addition, the physicians reconfirmed the general rules for how to use the VD3 reagents to the patients. These detailed explanations should be the most important point for subsequent therapeutic effects. Feldman et al.14 showed that frequent office visits improved the adherence of patients. Although the pharmacological efficacies of the three reagents do not differ much, VD3 rotation therapy may be a way to encourage patients with psoriasis who do not have high motivation to maintain sufficient adherence to the necessary long-term application to adhere to topical application again. We plan to look into more effective ways to maintain the clinical improvement obtained by this rotation therapy.

References

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