PHOENIX trials bring new hope for treatment of psoriasis

Medical Tribune July 2008 P10
David Brill

Ustekinumab seems to be an effective long-term treatment for patients with moderate-to-severe psoriasis, according to two randomized double-blind trials published last month in The Lancet.

The studies, named PHOENIX 1 and 2, found that more than three quarters of patients experienced a 75 percent improvement in symptoms at 12 weeks, following treatment with 90 mg ustekinumab given by subcutaneous injection at weeks 0 and 4. Furthermore, continued dosing every 12 weeks maintained the response up to a year in the majority of patients.

“These results are very impressive and are better than most of the current systemic treatments available and comparable to infliximab,” said Dr. Colin Theng, a consultant dermatologist at the National Skin Centre in Singapore.

Moreover, he added, the 12-weekly dosing schedule offers an advantage over other drugs which need to be taken more frequently.

Ustekinumab is a human monoclonal antibody which targets interleukins 12 and 23. The apparent success of the drug supports the theory that these proteins play a crucial role in the development of psoriasis, the authors say.

Theng, who is also president of the Psoriasis Association of Singapore, said that the drug was “a
very promising treatment for psoriasis.”

“Based on its efficacy and ease of use, it could certainly potentially be used in routine clinical practice. However, the drawbacks of this medication will include the longterm safety profile as this is a relatively new drug and the long-term side effects are unknown,” he said.

“There is also a risk of increased susceptibility of infections and the cost is likely to be prohibitive for its use as a first line treatment in psoriasis.”

PHOENIX 1 involved 766 patients. After 12 weeks, 67.1 percent of those taking ustekinumab had achieved a psoriasis area and severity index (PASI) score of 75 or higher, compared to only 3.1 percent of those who took placebo.

Those whose response continued up to 40 weeks were then randomized to maintenance therapy or withdrawal. At 1 year, those still taking ustekinumab had a significantly better maintenance of the PASI 75 response, according to the log-rank test (P<.0001).

The second trial, comprising 1,230 patients, found that PASI 75 at week 12 was achieved by 75.7 percent of patients taking 45 mg ustekinumab, 66.7 percent of those taking 90 mg ustekinumab, and 3.7 percent of those taking placebo. Those who had responded only partially to treatment at week 28 were re-randomized, either to continue their dosage every 12 weeks or escalate it to 90 mg every 8 weeks. By week 52, 68.8 percent of those in the dose escalation group had an improved response, compared to 33.3 percent of those whose therapy had remained unchanged.