MADRID – Renowned dermatologic clinical trialist Kim A. Papp, MD, PhD, is known to pick his words carefully, and the word he uses to describe the quality of life improvement documented in psoriasis patients treated with the novel investigational humanized monoclonal antibody bimekizumab is “phenomenal.”
was lead investigator in the previously reported phase 2b multicenter BE ABLE 1 trial, in which 250 patients with moderate to severe chronic plaque psoriasis were randomized double-blind to various doses of bimekizumab or placebo every 4 weeks for 12 weeks (J Am Acad Dermatol. 2018 Aug;79:277-86.e10. ). He was also lead investigator in the 48-week phase 2b BE ABLE 2 extension study. He presented the 60-week quality-of-life BE ABLE 2 results for the first time at the annual congress of the European Academy of Dermatology and Venereology.
“Small numbers, but the results are nonetheless very compelling,” said Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
Bimekizumab is unique in that it selectively neutralizes both interleukin-17A and -17F, two closely related proinflammatory cytokines which, when upregulated, synergize with other proinflammatory cytokines to drive psoriasis and other immune-mediated inflammatory diseases. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit only IL-17A, and brodalumab (Siliq) targets the IL-17 receptor A. The bimekizumab clinical trials program – a work in progress – aims to demonstrate that dual neutralization of IL-17A and -17F provides a more complete therapeutic approach in psoriasis, with greater efficacy and fewer safety concerns than with current biologics, the dermatologist explained.
In BE ABLE 1, the primary endpoint of at least a 90% reduction in Psoriasis Area and Severity Index (PASI90) response was achieved at week 12 in 46%-79% of patients randomized to bimekizumab in dose-dependent fashion. Those PASI90 responses were maintained with additional treatment out to week 60 in BE ABLE 2 in 80%-100% of patients.
Dr. Papp’s focus at EADV 2019 was on the quality-of-life improvement achieved in bimekizumab-treated patients, a benefit not captured by PASI scores. For this purpose, he and coinvestigators turned to the Dermatology Life Quality Index (DLQI), measured in structured fashion every 4 weeks out to week 60.
“We often forget that even though we’re looking at the patient from the outside, what’s really important is how well they respond to our treatments internally. The DLQI is not a perfect tool, but it’s the best tool we have available. It gives us a fairly good survey of the various domains that affect patients’ day-to-day living,” he said.
In BE ABLE 1, the proportion of week-12 PASI90 responders achieving a DLQI of 0 or 1 – indicative of essentially no disease impact on quality of life – increased rapidly up until week 8. At week 12, 70%-100% of the PASI90 responders in the various treatment arms had a DLQI of 0 or 1. This quality-of-life improvement, like the PASI90 response, proved durable: When the week-12 PASI90 responders were assessed at week 60 in BE ABLE 2, 76%-93% of them had a DLQI of 0 or 1.
The improvements in quality of life correlated with clinical response. BE ABLE enrollees had an average PASI score of 19 at baseline. Overall, 79% of those with an absolute PASI score of 0 at week 12 had a DLQI of 0 or 1 at that time, as did 95% of those with a PASI of 0 at week 60. A PASI of 1 was associated with a 77% likelihood of a DLQI of 0 or 1 at week 12 and an 82% rate at week 60. In contrast, patients with an absolute PASI of 2-4 at week 12 had a 46% rate of DLQI 0/1, and those with a PASI 2-4 at week 60 had a 50% chance of having a DLQI of 0/1.
Phase 3 clinical trials of bimekizumab totaling several thousand psoriasis patients are ongoing.
The BE ABLE trials were sponsored by UCB Pharma. Dr. Papp reported serving as a consultant to and/or recipient of research grants from UCB and dozens of other pharmaceutical companies.
SOURCE: Papp KA. EADV 2019 Abstract FC02.02.