Treatment of Psoriasis With Calcipotriene Plus Psoralen–UV-A–Bath Therapy

Oral photochemotherapy with psoralen (methoxsalen) plus UV-A irradiation (PUVA) and PUVA-bath therapy are highly effective for the treatment of moderate to severe psoriasis. Compared with the commonly used oral application of methoxsalen, bath water delivery has an equal or superior therapeutic efficiency and causes fewer adverse effects than oral delivery, particularly systemic adverse effects, owing to a virtual absence of systemic resorption. In addition, skin photosensitization is considerably shorter compared with that caused by orally administered methoxsalen, and significantly lower doses of UV-A radiation are necessary to clear skin lesions than when using oral PUVA therapy.^{1 - 2}

The cholecalciferol analog calcipotriene, alone and in combination with UV-B and systemic PUVA therapy, has been shown to have good therapeutic effects in treating psoriasis.^{3 - 4} We now report the superior effect of once-daily applications of calcipotriene ointment on the response of psoriasis to PUVA-bath therapy.

Twelve patients (7 men and 5 women; age range, 22-68 years) with moderate to severe chronic, stable, plaque-type psoriasis were enrolled in this study. Patients had received no systemic antipsoriatric drug therapy or phototherapy for at least 2 months and no topical treatment for at least 2 weeks before the study. The severity of the psoriasis was assessed by a modified Psoriasis Area Severity Index. Patients receiving scores of 8 to 15 were included in the study. No additional therapy was permitted for the study period of 10 weeks.

Patients soaked 4 times a week (Monday, Tuesday, Thursday, and Friday) for 20 minutes in a bath solution of 0.5 mg of methoxsalen per liter of water at 37°C, and were treated immediately afterward with UV-A irradiation (UVA 7000; Waldmann, Villigen-Schwenningen, Germany). The irradiance at a distance of 22 cm from the bulbs was approximately 10 to 15 mW/cm². The initial UV-A dose was 20% to 30% of the individual minimum phototoxic dose. The UV-A doses were gradually increased at each third treatment up to a maximum single UV-A dose of 3.5 J/cm².

In each patient, psoriatic plaques on the right side of the body were treated with topical calcipotriene, 50 µg/g, while lesions on the left side of the body were treated with emollient cream. Patients were advised to wash their hands after application of the calcipotriene ointment to prevent its transfer to the left side of the body. Topical treatment was applied once daily in the evening (at least 8 hours after phototherapy).

Clinical responses, including improved scores on the modified Psoriasis Area Severity Index, time to clearance, and cumulative UV-A doses needed for clearance of psoriatric plaques, were evaluated weekly by the same physician, who was blinded to which side of the body had received which treatment.

Both treatment modalities notably reduced Psoriasis Area Severity Index scores after 3 weeks. In 9 patients, scores were significantly lower in skin areas treated by PUVA-bath and calcipotriene than in areas treated with PUVA-bath therapy alone. Complete clearance was achieved in 9 of 11 patients who received both treatment protocols. However, plaques treated with the combination of PUVA-bath and calcipotriene cleared in a significantly shorter time (mean±SD time to clearance, 3.3±0/9 weeks; range, 2-5 weeks) than those treated with PUVA-bath monotherapy (mean±SD time to clearance, 5.3±1.1 weeks; range 4-7 weeks) (Figure 1). The mean±SD cumulative UV-A dose for all patients was 17.8±12.6 J/cm²(range, 4.2-39.4 J/cm²) for the lesions treated with calcipotriene plus PUVA-bath, and 31.8±8.0 J/cm² (range, 23.1-47.8 J/cm²) for the lesions treated with PUVA-bath alone (Figure 2).

These data indicate that calcipotriene in combination with PUVA-bath is superior to PUVA-bath therapy alone. Several studies have demonstrated that systemic PUVA therapy in combination with calcipotriene improved psoriasis more rapidly than systemic PUVA therapy alone. In addition, cumulative UV-A doses necessary for clearance of psoriasis were significantly lower than cumulative UV-A doses reached after oral PUVA therapy alone.^{3 - 4}

We found that the combination of topical calcipotriene with PUVA-bath therapy was more effective and cleared psoriatric plaques more rapidly than PUVA-bath therapy alone. Patients treated with combination therapy needed fewer irradiation sessions than those receiving PUVA-bath monotherapy. Therefore, cumulative UV-A doses needed for complete clearance were significantly lower.

The major long-term risk of photochemotherapy is the development of cutaneous malignancies. Little is known about the long-term risks of PUVA-bath therapy using methoxsalen as a photosensitizing agent. Lindelöf et al⁵ analyzed the relative risk of skin cancer in patients with psoriasis treated with different modes of PUVA therapy and found an increased frequency of skin cancer in patients treated with oral PUVA therapy vs patients treated with PUVA-bath therapy. However, in these studies trioxsalen was used for PUVA-bath therapy. Long-term data on the relative risk of skin cancer in patients treated with methoxsalen bath are not available. Thus, if a therapeutic agent used in combination with PUVA-bath therapy reduces the UV-A dose required for clearance of psoriasis, the long-term risk of cutaneous malignancy may be reduced. In addition, an improved response to combination treatment might benefit those patients whose lesions fail to clear with PUVA-bath therapy alone.