麻豆传媒

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 trial showed.

More than half the patients had a Physician Global Assessment (PGA) score of 0/1 (clear/nearly clear) 16 weeks after switching, increasing to 63% at 52 weeks. Quality of life (QoL) and psoriasis-related symptoms also improved in a substantial proportion of patients at 16 weeks, and the percentage continued to increase 52 weeks.

The study addressed an important issue frequently 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 continually see data on patients who had biologic exposure and then go on the study drug and they always seem to do as well as patients who are biologic naive, or they are not far off," said Warren. "What we really need to know in clinic is if a patient is starting to fail a drug ... having a suboptimal response, we then need to know how they get on with another drug. This study specifically addresses that question."

Investigators in the multicenter study enrolled patients with moderate/severe plaque psoriasis who had suboptimal response after at least 6 months with secukinumab (Cosentyx) or ixekizumab (Taltz). For the trial, suboptimal response was defined as a static PGA score of 2/3 and affected body surface area (BSA) of 3% to <10%.

The primary endpoint was PGA 0/1 at week 16. Key secondary endpoints included the proportion of patients achieving PGA 0, Dermatology Life Quality Index (DLQI) score of 0/1, and Psoriasis Symptom Score (PSS) of 0 at weeks 16 and 52, as well the proportion of patients who achieved PGA 0/1 at 52 weeks.

Data analysis included 252 patients, whose baseline characteristics were similar to those of patients enrolled in pivotal clinical trials of risankizumab, said Warren. The study population had a mean disease duration of 20.8 years, 40.5% had received two or more prior biologic agents, and mean duration on therapy prior to the switch was 2.1 to 2.6 years.

The primary analysis showed that 56.3% of patients had a PGA score of 0/1 at 16 weeks, increasing 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 the endpoints was evident at 4 weeks, and the percentage continued to increase throughout follow-up.

Treatment-emergent adverse events (AEs) were consistent with the safety profile that risankizumab demonstrated during the pivotal psoriasis studies, including presumed drug-related AEs (33.9%), severe and serious AEs (8.7%, 7.7%), discontinuation related to AE (3.3%), adjudicated major adverse cardiac events (0.7%), serious infections (1.1%), and malignancy (1.5%, decreasing to 0.7% after excluding non-melanoma skin cancer).

"I genuinely think this population is more difficult to treat than most populations that have usually been studied," said Warren. "There are very few clinical trials that have enrolled patients who are partially or completely failing other drugs, like we have defined here. Within that context, all primary and secondary endpoints were met ... and in fact there was an improvement in benefits. There were no new safety signals, which of course is reassuring."

Noting the "dramatic improvement" that occurred after the switch, AAD session moderator Andrew Blauvelt, MD, of Oregon Medical Research Center in Portland, wondered whether baseline body weight was a factor in the results.

"Did you look closely at weight to see whether the nonresponders are heavier versus the thinner patients?" he asked.

Body weight in the study population was similar to that in the pivotal trials of risankizumab and did not appear to be an explanation for response, Warren responded.

Session co-moderator Amy Paller, MD, of Northwestern University in Chicago, asked whether the treatment failure was primary or secondary, meaning patients originally responded and then lost the response over time. Given the length of treatment duration on prior biologics, failure was probably secondary, said Warren.

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