Psoriatic Arthritis Improves with New Treatment | Arthritis Information

In a 12-week randomized phase II trial, 42% of patients given the agent met ACR20 criteria for improvement versus 14% of a placebo group (P=0.0002), reported Alice Gottlieb, M.D., of Tufts Medical Center, and colleagues online in The Lancet.

With the more stringent ACR50 criteria as an endpoint, 25% of patients given ustekinumab reached the target compared with 7% of the placebo controls (P=0.0038).

Some 11% of patients in the ustekinumab group and none taking placebo met ACR70 criteria (P=0.0055).

There was no difference between groups in total and serious adverse events, the researchers found.

On the basis of these results, Dr. Gottlieb and colleagues wrote, "the efficacy and safety of two or four doses of ustekinumab compare favorably with available biologic agents for this disorder."

Ustekinumab has been approved in Europe for psoriasis. An application for U.S. marketing in psoriasis is pending.

Unlike most other monoclonal antibody drugs, which require IV infusion, ustekinumab is generally delivered subcutaneously.

The agent blocks interleukins 12 and 23 by binding to the P40 protein subunit that is a component of both. Previous studies have shown that this action disrupts the inflammatory cascade that is downstream of these interleukins, which plays an important role in psoriasis.

The phase II study was conducted at 24 sites in North American and Europe.

Dr. Gottlieb and colleagues randomized 146 patients to the two treatment groups. Mean duration of psoriatic arthritis was about five years, and patients had mean tender and swollen joint counts of about 17 and 8.5, respectively.

Mean Psoriasis Area and Severity Index scores at baseline were about 9.1.

Injections were given every week for the first four weeks. After twelve weeks, the study included a cross-over phase in which participants received two additional injections, at study weeks 12 and 16.

Those originally assigned to ustekinumab were given placebo during the cross-over phase, and those initially taking placebo then received the active drug. Patients were followed out to week 36.

The effects of ustekinumab appeared to be highly durable. During the cross-over period, the proportion of patients meeting ACR20 criteria -- the study's primary endpoint -- declined only slightly by week 36, to about 35%.

In the original placebo group, the fraction meeting ACR20 criteria jumped to more than 40% at week 16 and remained at that level through the remainder of the cross-over phase.

ACR50 and ACR70 responses did not last quite that long, but the proportion of patients meeting them stayed near levels for about 14 weeks after the last ustekinumab dose.

Thirteen patients in the placebo group and four assigned initially to ustekinumab discontinued treatment before week 12, primarily because of adverse events or inadequate therapeutic effect.

Most patients in the study had some kind of adverse event, but they were similar in number and kind between groups.

Even injection-site reactions were rare, with 4% of the ustekinumab group and none with placebo.

The most common events were upper respiratory tract infections and nasopharyngitis.

Dr. Gottlieb and colleagues urged that larger and longer-term studies be conducted.

In an accompanying editorial, Raquel Cuchacovich, M.D., and Luis Espinoza, M.D., both of Louisiana State University in New Orleans, said the study indicated that ustekinumab is "an attractive option for psoriatic arthritis."

However, they noted that the inflammatory pathways involved with psoriasis are complicated and not fully understood. They suggested that clinicians not take the safety findings in the current study totally at face value.

"We should . . . remain vigilant for potential complications due to the complex nature of cytokine pathways that are downregulated," they wrote.

They also pointed out that, as with any biologic agent, attention must be paid to "pharmacoeconomic issues" with ustekinumab.