Guidelines on Calcipotriol With or Without Betamethasone Dipropionate for Psoriasis Treatment

New evidence-based guidelines for the use of calcipotriol with or without betamethasone dipropionate in mild to moderate psoriasis treatment were recently published in the Journal of Dermatology.

Investigators conducted a systemic review, searching PubMed, Embase and MEDLINE as well as Chinese, Japanese, Korean, and Latin American databases for English-language publications from database inception until December 3, 2018. Clinical trials and observational studies of patients with psoriasis vulgaris treated either with 50 µg/g topical calcipotriol (Cal) or with a fixed-dose combination of 50 µg/g Cal and 500 µg/g betamethasone dipropionate (BD) ointment, gel and/or cream were included in the review. Investigators also used real-world evidence from noninterventional studies to help elucidate long-term disease control using Cal and Cal/BD. Based on a critical review of the published evidence and expert opinion, investigators formulated recommendations for clinical practice.

The systemic review included 37 publications, 28 of which were randomized controlled trials; 54.1% of the trials were conducted in Europe or North America. Most studies only evaluated psoriasis on the body rather than the scalp, and most were only concerned with adults. There was a wide range in grading criteria for disease severity across the publications; for example, mean Psoriasis Area and Severity Index (PASI) score ranged from 3 to 39. A consistent global endpoint for all trials was not found.

Studies with an induction phase had fixed-schedule dosing up to 12 weeks, such as once or twice daily. The continued treatment phases had a wide variety of dosing schedules. There were only 10 studies (27%) with a treatment duration longer than 12 weeks, ranging from 26 to 64 weeks.

All Cal and Cal/BD treatments improved psoriasis compared with baseline during the induction phase. In all 6 trials evaluating both Cal and Cal/BD, Cal/BD consistently led to greater clinical improvement than Cal alone during the induction phase. Cal/BD was also more effective than Cal alone during continued treatment phases.

Few studies directly compared the effectiveness of different dosing schedules of the same topical treatment; in studies that did, there was greater treatment success with more frequent Cal/BD application vs less frequent Cal/BD application. A study reported reduced recurrence with Cal when patients applied it to the entire area of the original lesion, even as the skin healed, and not limiting Cal application to the unhealed skin as the lesion got smaller.

Most studies collected data on adverse events and reported that treatments were generally “well tolerated,” and 4 studies reported that patients treated with Cal/BD displayed greater tolerance than those patients treated with Cal alone. In a study that the authors highlighted as “the most rigorous evidence,” 37.9% of patients treated with Cal alone for 48 weeks after 4 weeks of Cal/BD reported adverse events compared with 21.7% and 29.6% of patients on 2 different types of Cal/BD regimens (P <.001). The most common adverse events were burning, pruritus, and erythema.

Enhanced patient education on topical treatment application and offering telephone/email helpdesks and reminders led to greater response rates after 8 weeks vs standard of care (36.3% vs 31.3%, P =.0267).

There were several knowledge gaps due to limited data on the efficacy and safety of fixed daily regimens longer than 12 weeks, the safety and efficacy of Cal/BD or Cal in children, optimal treatment for non-responders to Cal/BD, and the efficacy of psoriasis evaluation instruments.

Based on the evidence available from the systemic review, the study authors were able to recommend the following guidelines for adults, not limited to issues affecting specific geographic or ethnic populations:

1. Treatment with Cal/BD up to 16 weeks on a fixed-treatment regimen, and up to 1 year on as “as needed” basis, is well tolerated and efficacious.

2. Treatment with Cal alone up to 20 weeks on a fixed-treatment regimen, and up to 52 weeks on as “as needed” basis, is well tolerated and efficacious.

3. The safety and efficacy profile of Cal/BD is more favorable than Cal alone when used on an “as needed” basis for up to 1 year.

4. Patients should be seen regularly by a dermatologist or primary care provider to assess their psoriasis and adjust their treatment as necessary.

5. Healthcare providers and patients should agree on a specific treatment goal when topical treatment is initiated, in order to determine when to begin long-term treatment or change the treatment regimen.

6. Healthcare providers and patients should agree on the application frequency of topical treatment during the continued-treatment phase, with consideration of the patient’s wishes and treatment expectations.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Zhao Y, Asahina A, Asawanonda P, et al. Systematic review and practical guidance on the use of topical calcipotriol and topical calcipotriol with betamethasone dipropionate as long-term therapy for mild-to-moderate plaque psoriasis. J Dermatol. 2021;48(7):940-960. doi:10.1111/1346-8138.15806