SAN DIEGO — Risankizumab, an experimental biologic, cleared more plaque psoriasis than ustekinumab (Stelara, Janssen) in a pair of phase 3 head-to-head trials.
After a year of treatment, risankizumab cleared the skin of more than half the patients, whereas ustekinumab — one of the most effective therapies on the market — cleared the skin of about one-quarter. Still, the clear superiority of risankizumab over other treatments already on the market was not demonstrated.
The results continue a string of “impressive successes” for new treatments that selectively suppress aspects of the immune system responsible for psoriasis, said Kenneth Gordon, MD, from the Medical College of Wisconsin in Milwaukee.
“We’ve made tremendous progress,” he said here at the American Academy of Dermatology 2018 Annual Meeting.
Eight biologic agents have already been approved by the US Food and Drug Administration (FDA) for psoriasis, but none of them work for all patients, and often they lose effectiveness over time, said session moderator Joel Gelfand, MD, from the University of Pennsylvania in Philadelphia. This trial illustrates how risankizumab might address some of this unmet need, he told Medscape Medical News.
Gordon and his colleagues conducted two identical trials — ultiMMa-1 (NCT02684370) and ultiMMa-2 (NCT02684357) — assessing a total of 797 adults with moderate to severe plaque psoriasis. Patients with any active inflammatory disease other than psoriasis or psoriatic arthritis were excluded from the studies.
Severe Psoriasis
In part A of the trials, participants were randomly assigned to an injection of risankizumab 150 mg, ustekinumab 45/90 mg, or placebo at baseline, and then received another injection 4 weeks later. From 1.0% to 4.1% of participants dropped out during this phase.
In part B of the trials, participants in the placebo group crossed over to risankizumab, and all patients received injections at 16, 28, and 40 weeks. From 2.1% to 5.0% of participants dropped out during this phase.
At 16 and 52 weeks, risankizumab was superior to ustekinumab on both the Psoriasis Area and Severity Index (PASI) and the Static Physicians Global Assessment (sPGA).
The researchers evaluated rates of PASI 90 and PASI 100 — the percent of patients achieving a reduction in PASI score of at least 90% and 100%, respectively — and rates of sPGA scores of 0 or 1, indicating complete or almost complete clearing.
The difference in efficacy between the drugs were all statistically significant at 16 and 52 weeks (P < .001).
Table. 16-Week Outcomes at the End of Part A
| Outcome | Risankizumab Group | Ustekinumab Group | Placebo Group |
|---|---|---|---|
| ultIMMa-1 | |||
| n | 304 | 100 | 102 |
| PASI 90, % | 75 | 42 | 5 |
| PASI 100, % | 36 | 12 | 0 |
| sPGA 0/1, % | 88 | 63 | 8 |
| ultIMMa-2 | |||
| n | 294 | 99 | 98 |
| PASI 90, % | 75 | 48 | 2 |
| PASI 100, % | 51 | 24 | 2 |
| sPGA 0/1, % | 84 | 62 | 5 |
At 52 weeks, when the placebo group had crossed over to risankizumab, the percentage of patients whose symptoms were completely cleared increased in both groups, but risankizumab was still superior to ustekinumab.
Table. 52-Week Outcomes at the End of Part B
| Outcome | Risankizumab Group | Ustekinumab Group |
|---|---|---|
| ultIMMa-1 | ||
| n | 304 | 100 |
| PASI 90, % | 82 | 44 |
| PASI 100, % | 86 | 21 |
| sPGA 0/1, % | 56 | 54 |
| ultIMMa-2 | ||
| n | 294 | 99 |
| PASI 90, % | 81 | 51 |
| PASI 100, % | 60 | 30 |
| sPGA 0/1, % | 83 | 55 |
In addition, at 52 weeks, more patients in the risankizumab group than in the ustekinumab group achieved a Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating a better quality of life.
The effects of risankizumab appear to be more durable, with dips in PASI 90 scores between injections of ustekinumab, but not risankizumab.
About 15% of patients experienced adverse events that were deemed to be related to the drugs, but most were not serious and the proportions were similar for the two drugs. In both the ultIMMa-1 and ultIMMa-2 trials, the most frequently reported risankizumab-emergent adverse event was upper respiratory tract infection. In ultIMMa-1, one patient in the risankizumab group presented with latent tuberculosis and was treated with rifampicin.
Table. Adverse Events at 52 Weeks
| Event | Risankizumab Group, % | Ustekinumab Group, % |
|---|---|---|
| ultIMMa-1 | ||
| Drug-related event | 12.5 | 15.2 |
| Serious drug-related event | 4.4 | 1.0 |
| ultIMMa-2 | ||
| Drug-related event | 15.1 | 23.4 |
| Serious drug-related event | 1.7 | 1.1 |
Risankizumab could be more effective because it has a slightly different mechanism of action, Gordon told Medscape Medical News. Ustekinumab blocks both interleukin (IL)-12 and IL-23, whereas risankizumab blocks only IL-23. It is possible that IL-12 actually has a beneficial role in psoriasis, he said.
Alternatively, risankizumab might bind more tightly to its molecular target or stick to that target longer than ustekinumab, he added.
It remains to be seen how risankizumab compares with other biologics approved for psoriasis, and with those in the pipeline, because head-to-head trials with other agents have not been conducted.
Secukinumab (Cosentyx, Novartis), ixekizumab (Taltz, Lilly), and brodalumab (Siliq, Valeant) all inhibit IL-17. They appear to be more effective than ustekinumab, Gordon pointed out, but when the ultIMMa-1 and ultIMMa-2 trials were being designed, these IL-17 inhibitors were not available for comparison.
In an update session on psoriasis treatments at the meeting, Leon Kircik, MD, from Indiana University in Indianapolis, said the excellent phase 2 results with risankizumab had raised his hopes, but with these phase 3 results, “I’m a little disappointed in this drug.”
“PASI 90 results,” he noted, “are not much better than what is already on the market.”
Still, risankizumab will be useful because patients and their providers need more treatments, Gelfand said. “One strategy doesn’t work for everyone, and one drug often doesn’t work forever,” he added. For example, the IL-17 inhibitors appear to work more rapidly, but dosing must be more frequent than with the IL-23 inhibitors.
A company spokesperson reported that AbbVie plans to submit a new biologic application to the FDA this year, with the aim to bring risankizumab to market in 2019.
The study was funded by AbbVie. Gordon and Gelfand report financial relationships with AbbVie. Gordon, Gelfand, and Kircik report relationships with multiple other companies developing psoriasis treatments.
American Academy of Dermatology (AAD) 2018 Annual Meeting: Abstract F061. Presented February 17, 2018.
Follow Medscape Dermatology on Twitter @MedscapeDerm and Laird Harrison @LairdH
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