Extension study reflects durable efficacy, safety of tildrakizumab for plaque psoriasis
The high-affinity, humanized, anti-interleukin-23-p19 monoclonal antibody tildrakizumab showed durable efficacy and safety for the treatment of chronic plaque psoriasis, according to the week 256 findings of the reSURFACE 1 trial.
A total of 506 individuals who completed the 64-week base trial with PASI ≥50* and received tildrakizumab within 12 weeks of completion entered the long-term open-label extension phase (week 64–256). Participants received the same tildrakizumab dose they were receiving at base study completion (n=239 [100 mg] and 267 [200 mg]). [AAD 2021, poster 25995]
Three-quarters of participants (72 percent [100 mg] and 78 percent [200 mg]) completed the extension phase. Partial responders (PASI 50 to ≤75) to tildrakizumab 200 mg continued the same dose; partial responders to tildrakizumab 100 mg were rerandomized to tildrakizumab 100 or 200 mg.
PASI 75, 90, and 100 responses at week 64 were respectively achieved by 87, 54, and 31 percent of tildrakizumab 100-mg recipients and 82, 52, and 27 percent of tildrakizumab 200-mg recipients. The end of the extension phase saw improvements in these percentages (91, 77, and 53 percent [100 mg] and 92, 88, and 57 percent [200 mg]).
The percentages of participants on tildrakizumab 100/200 mg with a PGA** 0/1 response by end of the extension phase (59/61 percent) were similar to that seen at week 64 (65/63 percent).
“[The] PASI and PGA response rates were high and durable over 5 years of treatment with tildrakizumab 100 and 200 mg,” noted study author Dr Andrew Blauvelt from the Oregon Medical Research Center, Portland, Oregon, US, and colleagues, in their presentation.
A post hoc analysis looked into the safety of both tildrakizumab doses over 5 years in the extension trial. Safety was assessed from EAIRs*** of drug-related adverse events (AEs) and serious AEs (SAEs). AEs/SAEs leading to discontinuation through 5 years were estimated as cumulative incidence per 100 patient-years (PY) exposure. There were 1,165 and 1,366 PYs of exposure to tildrakizumab 100 and 200 mg, respectively. [AAD 2021, poster 25997]
EAIRs of any drug-related AE were 6.6/5.5 events per 100 PY for tildrakizumab 100/200 mg. Drug-related SAEs (1.1/0.4 events per 100 PY) and discontinuations due to drug-related AEs (0.9/0.1 events per 100 PY) were uncommon in either tildrakizumab arm.
The most common individual AEs tied to tildrakizumab 100/200 mg were upper respiratory tract infections (EAIR, 0.9/1.5 events per 100 PY) and nasopharyngitis (EAIR, 0.4/1.0 events per 100 PY).
The most common type of drug-related AE tied to tildrakizumab 100/200 mg were infections and infestations# (3.3/3.7 events per 100 PY), while neoplasms## were the most common SAE (1.6/0.8 events per 100 PY).
“Because psoriasis is a chronic disease, it is important to understand the long-term safety profile of therapeutic agents used for its treatment,” noted Dr Pablo Fernández-Peñas from the Sydney Medical School, University of Sydney, NSW, Australia, and colleagues, in their poster presentation.
“[Our findings show that] through 5 years of treatment, the EAIRs of drug-related AEs, SAEs, and AEs leading to discontinuation were similar between tildrakizumab 100 or 200 mg, suggesting no dose-dependent safety effects,” they continued. “No new safety signals were observed ... [Tildrakizumab] treatment was well-tolerated with low rates of AEs.”
The long-term safety and efficacy data of reSURFACE 2 mirrored the reSURFACE 1 findings. [AAD 2021, posters 25993 and 25996] The initial findings of both reSURFACE trials have led to the approval of tildrakizumab for moderate-to-severe plaque psoriasis in the US, EU, Australia, and Japan. [Lancet 2017;390:276-288; Br J Dermatol 2018;179:615-622; Br J Dermatol 2020;182:605-617]