Abatacept fails to prevent psoriasis relapse after stopping ustekinumab
Blocking costimulatory immune response with abatacept did not prevent psoriasis relapse after ustekinumab discontinuation, reveals a study presented at ISDS 2018.
“Ustekinumab (anti‐IL‐12, 23) is FDA‐approved for psoriasis vulgaris, but relapse nearly always occurs after ustekinumab discontinuation,” said lead author Dr Dawn Smilek of the University of California San Francisco in San Francisco, California, US.
“Abatacept (CTLA‐4Ig) blocks costimulation by interfering with CD28‐B7 signalling, and is FDA‐approved for rheumatoid arthritis, juvenile idiopathic arthritis, and psoriatic arthritis,” he explained. The researchers sought to find out if costimulation blockade will prevent pathogenic immune response from reactivating following discontinuation of ustekinumab.
In the double-blind trial, 108 patients with moderate-to-severe psoriasis vulgaris were given subcutaneous injections of ustekinumab at weeks 0 and 4. Patients who achieved at least a 75 percent improvement in the Psoriasis Area and Severity Index (PASI 75) at week 12 were subsequently randomized 1:1 to continue ustekinumab treatment (n=46) or switch to abatacept (n=45), in addition to corresponding placebo. Ustekinumab dosing was at weeks 16 and 28, while abatacept was weekly from weeks 12 to 39. [ISDS 2018, abstract 60]
Participants were monitored for the primary outcome of psoriasis relapse up to week 88. Most of the patients discontinued treatment before week 88 was up (91 percent and 87 percent in the abatacept and ustekinumab arms, respectively).
Similar proportion of patients in the abatacept arm had psoriasis relapse compared with the ustekinumab arm (89 percent vs 80 percent; p=0.17).
Continuation of ustekinumab treatment during the randomized phase prolonged the time to relapse compared with switching to abatacept (median, 60 vs 40 weeks).
Twenty-four of the 91 randomized participants discontinued the study for reasons other than psoriasis relapse.
Serious adverse events or grade ≥3 adverse events were comparable between both arms, which according to the researchers, indicates that “sequential administration of ustekinumab followed by abatacept was safe and well‐tolerated … [but this] did not prevent psoriasis relapse following discontinuation of ustekinumab.”
“RNAseq analysis of serial skin biopsies is in progress to assess the effect of abatacept on the immune signature in psoriasis skin following ustekinumab discontinuation,” said Smilek.