Investigational Selective IL-23p19 Inhibitor Superior to Ustekinumab in PASI Response in Plaque Psoriasis
SAN FRANCISCO, CA—Treatment with BI 655066, a selective IL-23p19 inhibitor, resulted in PASI responses superior to those achieved with ustekinumab in patients with moderate-to-severe plaque psoriasis with or without concurrent psoriatic arthritis, reported Howard Sofen, MD, from the UCLA School of Medicine at the 2015 ACR/ARHP Annual Meeting.
"IL-23 is pivotal to the induction and maintenance of psoriatic plaques and has been implicated to have a role in psoriatic arthritis," said Dr. Sofen. He noted that IL-23 plays a role in the differentiation and maintenance of Th17 cells in psoriasis and psoriatic arthritis.
Dr. Sofen and colleagues compared the safety and efficacy of BI 655066, a humanized IgG1 monoclonal antibody that selectively inhibits the p19 subunit of IL-23 (and hence, the Th17 pathway), with the safety and efficacy of ustekinumab, an IL-12/23 inhibitor, in patients with moderate-to-severe plaque psoriasis with and without concurrent psoriatic arthritis.
For the Phase 2 study, 166 patients were randomly assigned to receive subcutaneous BI 655066 (18mg single dose at Week 0; or 90mg or 180mg at Weeks 0, 4, 16) or ustekinumab (45mg or 90mg at Weeks 0, 4, 16).
Patients' skin lesions were assessed through the Psoriasis Area and Severity Index (PASI) with the primary endpoint of PASI 90 (90% improvement in PASI score from baseline) at Week 12. Pain was measured by a visual analog scale (pain-VAS [0–100mm]) at Week 0 and at Weeks 4, 12, and 24 among patients with concurrent diagnosed or suspected psoriatic arthritis.
PASI 90 response at Week 12 was achieved by 30% in the BI 655066 18mg, 73% in the BI 655066 90mg, and 79% in the BI 655066 180mg groups, compared to 40% in the ustekinumab group (PASI 90 week 12 for BI 90mg and 180 mg pooled, vs. ustekinumab: P<0.0001), Dr. Sofen said.
Of the 46 patients with concurrent rheumatologist-diagnosed (n=13) or investigator-suspected (n=33) psoriatic arthritis, the proportions of patients achieving >50% decreases in pain-VAS from Week 0 at weeks 12 and 36 were 29% and 0% for the BI 655066 18mg group, 73% and 73% for BI 655066 90mg, and 50% and 82% for BI 655066 180mg, vs. 54% and 56% for ustekinumab.
For BI 655066 90mg and 180mg dose groups, reductions in the pain-VAS score were observed as early as 4 weeks, Dr. Sofen noted.
No dose-response relationship for any adverse events or safety endpoints were observed and rates were similar between treatment arms, he said. Adverse events incidences were comparable across all study groups. The most frequent adverse events for all study groups were infections and infestations, nasopharyngitis,nervous system disorders, headache, and musculoskeletal and connective-tissue disorders.
CASPAR criteria were not required to ascertain psoriatic arthritis and the only endpoint for psoriatic arthritis was pain-VAS, Dr. Sofen cautioned. "Joint counts and other relevant measures were not performed," he noted. "The study was not powered for statistical analysis in the subset of patients with psoriatic arthritis."
Overall, "selective blockade of IL-23p19 with BI 655066 was associated with superior cutaneous response compared with ustekinumab in patients with moderate-to-severe plaque psoriasis," Dr. Sofen said. "BI 655066 was well tolerated with a safety profile comparable to ustekinumab. Phase 3 studies are in preparation to investigate the long-term efficacy and safety of BI 655066 in psoriasis."