PsoriasisNet Article
News from the Psoriasis Research Pipeline

Visitors to this Web site often ask, “What is happening in psoriasis research?” Given recent scientific advances, this is not surprising. Genes
that can trigger psoriasis have been identified, and we now know that the immune system plays a key role. This discovery led to the much-publicized biologics research. What people may not know is that researchers continue to study other therapies. This article highlights other therapies in the research pipeline.

Topical Medications
Corticosteriods (also known as steroids, cortisones, glucocorticoids, and glucocorticosteriods) remain the most frequently prescribed treatment for mild to moderate psoriasis. Potent corticosteroids have the potential to clear or nearly clear psoriatic plaques more effectively than other topical therapies. Long-term use, however, can lead to irreversible thinning of the skin and decreasing effectiveness. Additionally, corticosteroids cannot be used around the eyes due to the risk of developing glaucoma.

Research continues to look for steroid-free alternatives. Recent studies show that two topical medications, calcitriol and tacrolimus, may hold promise.

Calcitriol. This topical form of vitamin D is used in some countries to treat psoriasis. One European study¹ concluded that calcitriol is almost as effective as the topical corticosteroid, betamethasone dipropionate, in clearing chronic plaque psoriasis. This study also found that patients treated with calcitriol experienced longer periods of remission than the patients treated with betamethasone dipropionate.

Several other studies have shown that calcitriol can effectively treat mild to moderate plaque psoriasis on sensitive areas, such as the face, hairline, and body folds. In one European study, patients said the redness, swelling, and stinging/burning were significantly less with topical calcitriol than with topical calcipotriene,² a synthetic form of vitamin D that is approved for treatment of psoriasis in the United States. Calcitriol has not been approved for use in the United States due to its potential to raise calcium levels in the blood. Raised calcium levels can cause kidney disease and other serious medical conditions.

Since calcitriol appears to be effective for treating sensitive areas and a topical medication that can effectively treat sensitive areas without causing irritation would greatly benefit patients, synthetic forms of calcitriol are being developed and tested. Synthetic forms have the potential to lessen serious side effects. Some patients with mild to moderate plaque psoriasis are finding calcitriol helpful.³

Tacrolimus. In pill form, this medication is a potent immunosuppressant that is used to prevent organ-transplant rejection. Oral tacrolimus also can effectively treat severe plaque-type psoriasis that does not respond to other treatment. Due to its ability to suppress the immune system, oral tacrolimus is reserved for treating severe psoriasis that is not helped by other therapy.

Tacrolimus ointment, while not yet approved for this use, is effective in treating inverse psoriasis and psoriasis on the face. Recently, an exploratory study⁴ was conducted to find out if tacrolimus ointment could effectively treat plaque psoriasis found on other areas of the body when combined with 6% salicylic acid gel. Salicylic acid can help topical medication penetrate the skin. The study found that combining 0.1% tacrolimus ointment and 6% salicyclic acid gel, which helps remove scale, proves effective and is well-tolerated. A total of 24 adults with plaque-type psoriasis completed the 12-week study. There was greater clearance of plaques treated with salicylic acid plus tacrolimus than those treated with salicylic acid alone.

This was a very small, short-term study. More research is needed to determine if tacrolimus ointment can be used safely and effectively to treat mild to moderate plaque psoriasis.

Systemic
Topical medications and phototherapy target psoriasis lesions from the outside. Systemic medications, which are swallowed or injected, provide more powerful psoriasis treatment. However, side effects from systemic medications used to treat psoriasis often require that a medication not be used long term. The search continues for an effective and safer systemic medication that can be used long term.

Most of this research now focuses on the biologics. However, clinical trials continue to study other systemic medications. A medication known as fumaric acid esters is being studied.

Fumaric acid esters. This medication has been used in Germany since 1959 to treat psoriasis.⁵ Today, a few other European countries use this medication. Reports indicate that fumaric acid esters improve psoriasis for the majority of patients prescribed this treatment.⁶

However, many patients quit taking this medication due to common side effects that include flushing, diarrhea, nausea, and stomach pain. A less common, but more severe, side effect is the potential for kidney damage. For this reason, patients must be closely monitored, and usage is usually restricted to people with severe psoriasis who have not been helped by other treatments. Despite these side effects, some patients have successfully taken this medication for as long as 14 years.

Recent clinical trials conducted in Europe studied a new formulation, currently called BG00012, which is much less likely to cause diarrhea, nausea, and stomach pain. A phase II study⁷ — the phase in which the safety and effectiveness are studied in volunteers who have the condition — concluded at the end of the 24-week trial that BG00012 consistently improves psoriasis and is tolerable.

A total of 144 patients with plaque, guttate, erythrodermic, palmoplantar, or pustular psoriasis were enrolled in this study. Each patient had psoriasis for at least one year. Improvement was seen as early as two weeks. At week 12, 64% of patients taking 240 milligrams achieved a 50% improvement and 42% experienced a 75% improvement as measured by the Psoriasis Area and Severity Index (PASI), which measures improvements in severity. By comparison, 50% of the patients taking 120 milligrams spaced evenly throughout the day scored a PASI 50.

Common side effects were flushing and inflammation of the nasal passage and pharynx. These were mild and disappeared without treatment. The gastrointestinal side effects — diarrhea, nausea, and stomach pain — that are common in other formulations were reported in only one patient.
These finings indicate that BG00012 may be effective and less toxic than other currently approved systemic medications. Phase 3 studies are underway. One phase III trial⁸ is looking at the safety and effectiveness of BG00012 in patients with chronic plaque psoriasis.

Systemic Plus Topical
Research also is beginning to investigate the effects of combining biologics with other psoriasis treatments. Recently, a study looked at treating lesions with topical calcipotriol, a synthetic form of vitamin D approved to treat psoriasis, when a patient is receiving the biologic, alefacept.

Alefacept plus topical calcipotriol. A total of seven patients with moderate to severe plaque psoriasis participated in this study designed to find out if there was improved clearance when patients applied the topical medication, calcipotriol, to their lesions while receiving the biologic, alefacept.⁹ Each patient received alefacept once a week for 12 weeks. During these 12 weeks, each patient was instructed to apply calcipotriol cream every other day to all but one lesion.

During the first 12 weeks, adding calcipotriol resulted in faster improvement. When the psoriasis required additional treatment with alefacept, the patients again treated all but one lesion with topical calcipotriol. During the second 12-week period, calcipotriol did not cause faster clearing.


References:
¹ Camarasa JM et al. “Calcitriol shows greater persistence in treatment effect than betamethasone dipropionate in topical psoriasis therapy.” Journal of Dermatologic Treatment, 2003 January;14(1):8-13.

² Ortonne JP et al. “Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas.” British Journal of Dermatology. 2003 February;148(2):326-33.

³ Lebwohl, M. “Psoriasis: New Developments.” Presented at the 63^nd Annual Meeting of the American Academy of Dermatology: Symposium 302. February 2005: New Orleans.

⁴ Carroll, CL et al. “Topical tacrolimus ointment combined with 6% salicylic acid gel for plaque psoriasis treatment.” Archives of Dermatology. 2005 January;141(1):43-6.

⁵ Mrowietz U et al. “Dimethylfumarate for psoriasis: more than a dietary curiosity.” Trends in Molecular Medicine. 2005 January;11(1):43-8.

⁶ Lebwohl M et al. “Treatment of psoriasis. Part 2. Systemic therapies. Journal of the American Academy of Dermatology. 2001 November;45(5):649-61.

⁷ Langner A et al. “Results of a phase 2 dose-ranging and safety extension study of a novel oral fumarate, BG00012, in patients with severe psoriasis.” Presented at the 63^rd Annual Meeting of the American Academy of Dermatology: Poster P2787. February 2005: New Orleans.

⁸ Mrowietz U et al. “A novel formulation of an oral fumarate, BG00012, in patients with moderate to severe plaque psoriasis: a phase 3 study.”  Presented at the 63^rd Annual Meeting of the American Academy of Dermatology: Poster P2743. February 2005: New Orleans.

⁹ van Duijinhoven MWFM et al. “Effects of alefacept and alefacept in combination with calcipotriol on epidermal cell populations in psoriatic lesions.” Poster presented at the 63^rd Annual Meeting of the American Academy of Dermatology: Poster P2742. February 2005: New Orleans.

An educational program brought to you by the American Academy of Dermatology.

For an overview, visit the AAD pamphlet Psoriasis and Psoriatic Arthritis.