New Treatments for Psoriasis

New Treatments for Psoriasis

New Treatments for Psoriasis

For years, the mainstays of psoriasis treatment have been steroid creams, coal tar preparations, and moisturizers. For mild rashes, these have been sufficient. For severe psoriasis, people have resorted to immunosuppressive chemotherapy, such as methotrexate and cyclosporin, which are usually effective but have severe short-term and long-term side effects.

Here are some of the exciting recent developments:

The Vitamin D Family

Complete remission of psoriasis came as an unexpected side effect when a form of oral vitamin D3, called calcitriol, was used to treat osteoporosis (Medical Journal of Osaka University, 1985; 35:51-54). Its use was limited, though, because of its tendency to raise calcium levels too high, causing side effects such as kidney stones.

Next, topical treatment with calcitriol was tried, with 84% reporting complete clearance or marked improvement (British Journal of Dermatology, 1986; 115:421-429). This topical form could be quite irritating to the skin and, when used in large amounts, still raised calcium levels in the body. Researchers tried several variations to achieve less topical irritation and fewer oral side effects. Now several new forms are available, including calcipotriol, tacalcitol, and KH1060.

Of the three, calcipotriol (also called MC903, calcipotriene, and Dovonex) is the most widely used. Calcipotriol is 100 to 200 times less likely than calcitriol to cause side effects (Pharmacology and Toxicology, 1995; 77:241-246).

Calcipotriol has been proven safe and effective in children aged 2 to 14 years (Journal of the American Academy of Dermatology, 1997; 36:203-208). It now looks like tacalcitol will be even better tolerated than calcipotriol.

The Vitamin A Family

Topical retinoic acids were a great breakthrough in acne treatments, but when they were tried on patients with psoriasis, the early results were disappointing. Effective oral forms for psoriasis were later developed (similar to Accutane), but they had the disadvantage of high levels of toxicity. Recently, fourth-generation retinoids, including AGN190168 (also called tazarotene, Tazorac, and Zorac), have been shown to be effective topical therapies for psoriasis.

Tazarotene gel administered once or twice daily results in significant improvement as quickly as 1 week (Archives of Dermatology, 1998; 134:57-60). Importantly, the improvement was maintained for 8 to 12 weeks after stopping treatment. When used as a single agent, it is the most cost-effective way to achieve a disease-free period (Clinical Therapeutics, 1998; 20:851-869). Systemic absorption of tazarotene appears to be very low, leading to no systemic side effects.

Tonsillectomy?!?!

For children whose psoriasis is triggered by throat infections or made worse following strep or impetigo, tonsillectomy and adenoidectomy may be an option. One recent article reports complete freedom from rash during the 16-month follow-up after this simple surgery to remove lymph tissue (Ear Nose and Throat Journal, 1999; 78:155-158).

Ultraviolet Radiation

Natural sun exposure helps in psoriasis. This led to several attempts to improve on this effect. PUVA, a form of ultraviolet radiation, has been used for 25 years in psoriasis treatment and is one of the most common procedures today in dermatology (Journal of Dermatological Science, 1999; 19:78-88). Recent refinements in PUVA regimens have improved the results (British Journal of Dermatology, 1999; 140:661-666). Unfortunately, PUVA is generally not considered safe for children.

Even better results have now been achieved with narrow-band UVB phototherapy. In half of those treated, psoriasis cleared totally within 8 to 10 weeks (Photodermatology, Photoimmunology, and Photomedicine, 1999; 15:81-84). UVB phototherapy is approved for use in children (Pediatric Dermatology, 1996; 13:406-409).

People who bathe in the salt water of the Dead Sea in natural sunlight have been noted to have dramatic, complete improvement of their psoriasis (British Journal of Dermatology, 1998; 139:1012-1019). Trips to the beach or saltwater in the bathtub followed by sunbathing can be a pleasant addition to psoriasis therapy. Use sufficient sunscreen to prevent burning.

Immunosuppressives

Cyclosporin is a powerful immunosuppressive drug originally used to make heart, liver, and kidney transplants possible. The dramatic effect of oral cyclosporin in psoriasis was initially discovered in 1979 (New England Journal of Medicine, 1979; 301:555). Because of the side effects associated with cyclosporin use, treatment is usually reserved for patients with severe, widespread psoriasis. In most patients, remission of psoriasis is usually achieved within 8 weeks of treatment.

Topical cyclosporin is almost completely ineffective, probably due to the large size of the cyclosporin molecules.

FK506 (also called tacrolimus and Prograf) is a new immunosuppressive that is very similar to cyclosporin. Oral use has similar dramatic results for psoriasis and similar toxicity.

The FDA has recently approved topical FK506. The preliminary studies on severe eczema, showing that the topical form works spectacularly, are very exciting (New England Journal of Medicine, 1997; 337:816-821). The long-term side effects are still unknown, but this may be a great choice for those with psoriasis.

Three other similar topical compounds, SDZ281240, SDZASM981, and A86281, are also generating excitement, as are several other topical formulations that work by different mechanisms (Drug Discovery Today, 1999; 4:222-231).

Recently, new classes of biologic agents that have immunosuppressive action have been used to treat patients with moderate to severe psoriasis. A review of the literature published in July 2008 found that Infliximab, an immunosuppressive agent, was significantly superior to all other interventions (including the other immunosuppressives such as adalimumab, efalizumab, etanercept, and cyclosporine). Patients on Infliximab had a 77% improvement compared to patients on no therapy (Br J Dermatol. 2008 Jul 4).

Antibodies

Another interesting approach is to administer antibodies that specifically target the overactive molecules in psoriatic skin. Injections of OKTcdr4a every other day for a total of three injections resulted in significant improvement that lasted for a month (Journal of Autoimmunity, 1998; 11:53-62). Another antibody, ABX-IL8, is currently in a placebo-controlled trial for treatment of patients with moderate to severe psoriasis (Drug Discovery Today, 1999; 4:222-231).

Calcipotriol and tazarotene are ready to go as easy-to-use gels. Both of these have set new directions in psoriasis research, so that even better vitamin D3-based and vitamin A-based medicines are likely to be available soon. Topical FK-506 is also now available. And, as we’ve discussed, whole new types of psoriasis medicines are in the pipeline.

So far, we’ve been looking at single agents.

Combination treatment will offer the best solutions. We already know that when tazarotene is used with topical steroids, the combination is much more powerful and has fewer side effects than when used alone (Cutis, 1999; 63:41-48). When used with phototherapy, tazarotene makes UVB treatment even more effective (Journal of the American Academy of Dermatology, 1998; 39[suppl]:144-148).

Work closely with psoriasis experts to select the best combination for your child. I strongly recommend that anyone with more than mild psoriasis connect with the National Psoriasis Foundation, a nonprofit group of people with psoriasis, their families and friends, and medical professionals.

Reviewed by: Khanh-Van Le-Bucklin, Rebecca Hicks
Last reviewed: August 28, 2008
Dr. Alan Greene

Article written by

Dr. Greene is the founder of DrGreene.com (cited by the AMA as “the pioneer physician Web site”), a practicing pediatrician, father of four, & author of Raising Baby Green & Feeding Baby Green. He appears frequently in the media including such venues as the The New York Times, the TODAY Show, Good Morning America, & the Dr. Oz Show.

 

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