麻豆传媒

VIENNA -- Costimulatory blockade with abatacept (Orencia) did not prevent psoriasis relapse after discontinuation of ustekinumab (Stelara), researchers reported here.

Through week 88, about 91% of the 45 patients who took ustekinumab followed by abatacept had relapses compared with 87% of the 46 patients who took ustekinumab throughout the course of the study (P=0.405), according to Dawn Smilek, MD, PhD, of the University of California San Francisco.

"It doesn't look like abatacept prolonged the effectiveness of treatment with ustekinumab in these patients," she said at a poster presentation at the Inflammatory Skin Disease Summit. "Relapses occurred earlier in the abatacept arm where the last dose of ustekinumab was administered at 4 weeks compared to the ustekinumab arm of the trial where the last dose was administered at 28 weeks."

Smilek told 麻豆传媒 that ustekinumab is the standard of care for almost all patients diagnosed with moderate‐to‐severe psoriasis vulgaris, but these patients do relapse when the the agent is withdrawn.

"The idea was that if you introduced abatacept at a time of disease quiescence, and created a costimulatory blockade, that you would prevent reactivation of pathogenic cells," she explained. "We thought we could do this by giving ustekinumab first, and then introducing either abatacept or continuing ustekinumab."

Participants with moderate‐to‐severe psoriasis vulgaris received subcutaneous ustekinumab at weeks 0 and 4; at week 12, 91 participants who achieved Psoriasis Area and Severity Index (PASI) ≥75 response were randomized 1:1 to blinded treatment with either abatacept (median age 51, 60% women, 80% white, baseline PASI 16) or ustekinumab (median age 44, 70% women, 91% white, baseline PASI 17), and corresponding placebo.

Patients were then observed for relapses through week 88, Smilek said.

"Discontinuation for reasons other than psoriasis relapse occurred in 24/91 participants. In the ustekinumab arm, the median time to relapse was 60 weeks (95% CI 56‐68). In the abatacept arm, the median time to relapse was 40 weeks (95% CI 40‐52)," the authors stated.

There was no significant difference in serious adverse events or grade ≥3 adverse events between the two arms, they added. Smilek noted that the treatment regimen was safe and well t0lerated, "but abatacept did not prolong the time to relapse."

The researchers said RNA sequencing analysis of serial skin biopsies is in progress to assess the effect of abatacept on the immune signature in psoriasis skin following ustekinumab discontinuation. "Even though we did not observe a clinical benefit with abatacept, we want to see if there was any effect of abatacept on gene expression," Smilek explained.

Michele Green, MD, of Lenox Hill Hospital in New York, told 麻豆传媒, "Abatacept can work well in a subset of patients with psoriasis when other agents fail. It was a good idea to try and combine two agents such as ustekinumab and abatacept as they did in the study."

"Unfortunately combining these two agents did not have any meaningful benefit for the psoriatic patients," said Green, who was not involved in the study. "I do believe that there is a subset of patients who would benefit from two agents rather than one, but it may be trial and error in finding the best combination of treatment for this autoimmune disease."