BOSTON, Massachusetts—Ustekinumab (CNTO 1275), a new monoclonal antibody that blocks interleukin (IL)-12 and IL-23 (IL-23), may help thwart the pain, swelling and lesions of psoriatic arthritis (PsA).The new Phase 2 study, which appears in The Lancet,¹ found that the new drug reduces signs and symptoms of PsA and clears up lesions when compared with placebo.

"This is a positive development for patients living with the joint pain and swelling that characterizes the disease, even as more research is needed to further test the efficacy of this treatment in psoriatic arthritis," said lead researcher Alice Gottlieb, MD, the chairperson of the department of dermatology at Tufts Medical Center in Boston, in a press release. Ustekinumab is also being studied for treatment of moderate-to-severe plaque psoriasis.

Ustekinumab Phase 2 crossover PsA data look good

At week 12 of the new study, 42% of patients given 63 or 90 mg of ustekinumab at weeks 0, 1, 2, and 3 showed significant improvement in their pain, stiffness and other symptoms defined by the American College of Rheumatology (ACR20) score, compared with 14% of patients who received placebo at the same time points.

By week 36, 33 weeks after their last dose, approximately three-quarters of patients who had achieved ACR 20 sustained the improvement in their PsA symptoms. Moreover, at week 24, 12 weeks after their initial ustekinumab dose, 51% of patients who had initially received placebo at weeks 0, 1, 2, and 3 achieved ACR 20 following two doses of ustekinumab at weeks 12 and 16.

Of patients who had plaque psoriasis on at least 3% of their body, 52% of those who received 63 or 90 mg of ustekinumab at weeks 0, 1, 2, and 3 achieved at least a 75% improvement in psoriasis from baseline as measured by the Psoriasis Area and Severity Index (PASI 75) at week 12, compared with 5% of patients receiving placebo (P < 0.001).

The proportion of patients with at least one adverse event was similar between patients in both groups throughout the 12-week placebo-controlled part of the study. There were no deaths, no reports of malignancy, tuberculosis, or serious infections in either group. Through week 36, after the placebo crossover, the pattern of adverse events was similar to that observed through week 12 of the trial, the study showed.

“Larger studies undertaken over a longer period than ours are needed to further characterize ustekinumab for treatment of PsA,” the study authors conclude.

Psoriatic arthritis and ustekinumab: Translating research into practice

The new data suggest that IL-12 and IL-23 p40 cytokines may play a significant role in the pathogenesis of PsA. Previous genetic studies have pointed to a role for the same cytokines and products in psoriasis, explained James Elder, MD, PhD, a professor in the department of dermatology at the University of Michigan in Ann Arbor. Ustekinumab targets the product of IL12b – p40, which is one of the genes thought to confer an increased risk for psoriasis, he said.

“It’s going to be a great drug for psoriasis,” Dr. Elder told MSKreport.com. “I don’t think it will only be for people who carry the risk allele for 1L12b,” he said, suggesting it may have an even larger population in terms of efficacy.

As far as where it will fit in his arsenal for the treatment of psoriasis, “my strategy is to reserve the use of any expensive biologic agent for people who can't tolerate or who at present aren’t treated well by methotrexate.”

References

1. Gottleib A, Menter A, Mendelsohn A, et al.  Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomized, double-blind, placebo-controlled, crossover trial. Lancet. 2009; doi:10.1016/SO140-6736(09)60140-9 [published online ahead of print  February  12, 2009].