New phase 3 IMMhance findings show durable, sustained effect of the IL-23 inhibitor on a 12-week dose regimen.
Andrew Blauvelt, MD, MBA
Risankizumab (SKYRIZI) showed early efficacy and continued tolerability and safety through a two-year trial designed to assess treatment withdrawal in patients with moderate to severe plaque psoriasis.
In new findings from the phase 3 randomized, double-blind IMMhance clinical trial comparing the subcutaneous selective interleukin 23 (IL-23) inhibitor to placebo in patients with plaque psoriasis, investigators reported risankizumab’s superior efficacy in static Physician Global Assessment (sPGA) and Psoriasis Area and Severity Index (PASI) achievements over 16 weeks, as well as sustained benefit at 2 years.
The findings provide further evidence of benefit with a 12-week regimen of the monoclonal antibody for moderate to severe plaque psoriasis.
A team of investigators, led by Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, noted that in the clinical trial history of 12-week dosage risankizumab, the selective inhibitor has shown consistently strong efficacy in PASI 90 metrics up to 52 weeks from baseline.
The therapy has also shown greater safety and tolerability and similar efficacy to competitor agents that inhibit IL-17 over a similar period of time. Blauvelt and colleagues observed that selective IL-23 inhibition could offer greater safety benefits versus such biologics.
In accordance, the team conducted the IMMhance trial with 507 eligible patients with stable, moderate to severe chronic plaque psoriasis for at least 6 months. Patients were also qualified if they had longer, body surface area involvement of ≥10%, PASI ≥12, and sPGA ≥3.
Patients were randomized 4:1 to 150 mg risankizumab or placebo, at weeks 0 and 4. All patients then received risankizumab at week 16. Any patients randomized to risankizumab who achieved sPGA 0/1 were again randomized 1:2 at week 28 to either risankizumab or placebo every 12 weeks.
For the initial portion of the trial, investigators assessed for co-primary endpoints of proportion of patients achieving PASI 90, and sPGA score of 0/1 at week 16. In the latter half of the trial, the team assessed for proportion of rerandomized patients achieving sPGA 0/1 at week 52, and a secondary endpoint of such rates at week 104.
Mean patient age was 51 years (IQR, 38-60), with a majority (70.2%) being men. At week 16, nearly three-fourths (73.2%) in the treatment group achieved PASI 90, versus just 2% of placebo patients. Another 83.5% of patients on risankizumab achieved sPGA 0/1 scores, versus 7% of placebo patients (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7-76.0; sPGA 0/1: 76.5%; 95% CI, 70.4-82.5; P <.001).
Patients treated with risankizumab (45.7%) and placebo (49%) reported similar rates of treatment-emergent adverse events in the first part of the trial, and such rates remained stable through the latter half.
At 28 weeks, investigators rerandomized 336 patients to risankizumab (n = 111) or treatment withdrawal (n = 225). Another 87.4% of patients receiving therapy achieved sPGA 0/1 at week 52, versus 61.3% of placebo patients. At week 104, sPGA 0/1 was achieved by 81.1% of risankizumab patients and 7.1% of placebo patients (placebo-adjusted differences at week 52: 25.9%; 95% CI, 17.3-34.6; at week 104: 73.9%; 95% CI, 66.0-81.9; P <.001).
Blauvelt and colleagues concluded their findings indicate the first benefit-risk profile of risankizumab to extend to 2 years for chronic plaque psoriasis. They added that a majority of patients (55.4%) had already been exposed to biologic therapy prior to the trial, showing the IL-23 inhibitor’s particular long-term, durable benefit.
“Together, these findings support the use of 12-week risankizumab dosing as an efficacious and safe regimen for maintenance of clinical efficacy in patients with moderate to severe plaque psoriasis,” they wrote.
The study, “Efficacy and Safety of Continuous Risankizumab Therapy vs Treatment Withdrawal in Patients With Moderate to Severe Plaque Psoriasis,” was published online in JAMA Dermatology.