NEW ORLEANS — Plaque psoriasis that responded inadequately to an interleukin (IL)-17 inhibitor often had deep and durable responses after switching to the IL-23 inhibitor risankizumab (Skyrizi), a long-term prospective study showed.
More than half of the patients had a Physician Global Assessment (PGA) score of 0/1 (clear/almost clear) at 16 weeks post-switch, which increased to 63% at 52 weeks. Quality of life (QoL) and psoriasis-related symptoms also improved in a significant proportion of patients at 16 weeks, and the percentage continued to increase at 52 weeks.
The study addressed an important problem commonly encountered in clinical practice, said Richard Warren, PhD, of the University of Manchester in England, at the American Academy of Dermatology (AAD) annual meeting.
“In pivotal phase III clinical trials, we continue to see data from patients who have had biological exposures and then take the study drug, and they always seem to do as well as patients who are biologically naïve or not far off,” said Warren . “What we really need to know in the clinic is when a patient is starting to fail on a drug…if they are responding suboptimal, then we need to know how they are doing on another drug. This study specifically addresses that question.”
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Investigators in the multicenter study enrolled patients with moderate/severe plaque psoriasis who had had a suboptimal response to secukinumab (Cosentyx) or ixekizumab (Taltz) after at least 6 months. For the study, suboptimal response was defined as a static PGA score of 2/3 and an affected body surface area (BSA) of 3% to
The primary endpoint was PGA 0/1 at week 16. Key secondary endpoints included the proportion of patients achieving a PGA 0, a Dermatology Life Quality Index (DLQI) score of 0/1, and psoriasis at weeks 16 and 20 -Symptoms score (PSS) of 0 achieved 52, and the proportion of patients achieving PGA 0/1 at 52 weeks.
The data analysis included 252 patients whose baseline characteristics were similar to patients who had participated in pivotal clinical trials of risankizumab, Warren said. The study population had a mean disease duration of 20.8 years, 40.5% had previously received two or more biological agents, and the mean duration of therapy prior to switching was 2.1 to 2.6 years.
The primary analysis showed that 56.3% of patients had a PGA score of 0/1 at week 16, which increased to 63% at week 52. All other secondary endpoints also improved from week 16 to week 52:
- PGA 0: 19.8% to 26.2%
- DLQI 0/1: 38.9% to 46.5%
- PSS 0: 20.2% to 27.4%
Improvement in all endpoints was evident at 4 weeks and the percentage continued to increase during follow-up.
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Treatment-emergent adverse events (AEs) were consistent with the safety profile demonstrated by risankizumab during the pivotal psoriasis studies, including presumed drug-related AEs (33.9%), severe and serious AEs (8.7%, 7.7%), discontinuation associated with AEs (3.3%), confirmed serious adverse cardiac events (0.7%), serious infections (1.1%) and malignancy (1.5%, decreased to 0.7% after excluding Hellem skin cancer).
“I really think this population is more difficult to treat than most populations that have typically been studied,” Warren said. “There are very few clinical trials that have enrolled patients who have partially or completely failed other drugs, as we have defined here. In this regard, all primary and secondary endpoints were met… and indeed there was an improvement in benefit. There were no new safety signals, which of course is reassuring.”
AAD session moderator Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, noted the “dramatic improvement” that occurred after the switch and wondered if baseline body weight was a factor in the results.
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“Did you look closely at the weight to see if the patients who didn’t respond are heavier than the thinner patients?” he asked.
Body weight in the study population was similar to that in the risankizumab pivotal studies and did not appear to explain the response, Warren replied.
Session co-moderator Amy Paller, MD, of Northwestern University in Chicago, asked whether treatment failure was primary or secondary, meaning that patients initially responded and then lost response over time. Given the duration of treatment with previous biologics, the failure was likely secondary, Warren said.
disclosure
The study was supported by AbbVie.
Warren announced relationships with AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Amgen, Arena Pharmaceuticals, Avillion, Bristol Myers Squibb, Boehringer Ingelheim, Sanofi and UCB.
Main source
American Academy of Dermatology
Reference: Warren RB, et al “Efficacy and Safety at 52 Weeks in Psoriasis Patients Switching to Risankizumab After Suboptimal Response to Secukinumab or Ixekizyumab” AAD 2023.
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