Tildrakizumab yields durable responses for psoriasis
Long-term use of the humanized immunoglobulin G1K monoclonal antibody tildrakizumab generated durable responses in adult patients with moderate-to-severe chronic plaque psoriasis*, according to the results of the 3-year extension phases of reSURFACE 1** and 2*** presented at AAD 2019.
The reSURFACE 1 trial randomized 638 individuals (mean age 47.0 years, 67.6 percent male) to receive tildrakizumab 100 or 200 mg every 12 weeks. Of these, 506 (n=239 and 267 for 100 and 200 mg, respectively) entered the long-term extension phase (up to 192 weeks) upon achieving ≥50 percent improvement in Psoriasis Area and Severity Index score (PASI 50) at base study completion. The efficacy analysis was concluded at week 160 due to a drop in the number of participants. [AAD 2019, abstract 10508]
More than half of 100-mg recipients achieved PASI 75/90 at weeks 64 and 160 (87.8 percent/53.8 percent [week 64] and 84.4 percent/57.6 percent [week 160]). The rates were similar in the 200-mg arm (81.6 percent/52.4 percent [week 64] and 75.4 percent/50.8 percent [week 160]).
At week 160, 62.4 percent and 57.1 percent of patients receiving tildrakizumab 100 and 200 mg, respectively, achieved a Physician’s Global Assessment (PGA) response.
Fourteen percent of participants discontinued treatment at week 160, primarily due to patient withdrawal (5.7 percent), adverse events (AEs; 3.4 percent), and loss to follow-up (2.8 percent).
After almost 5 years of treatment, the cumulative number of patients with AEs of interest was low with both tildrakizumab dosages (<1.6 events/100 patient-years [PY]). Confirmed major adverse cardiovascular events (MACE) and drug-related hypersensitivity AEs occurred at very low rates (≤0.8 events/100 PY).
Similar results were observed in the extension phase of reSURFACE 2 (n=381 and 349 for tildrakizumab 100 and 200 mg, respectively), where a majority of participants achieved PASI 75/90 responses at week 52 (92.3 percent/69.9 percent [100 mg] and 88.7 percent/56.7 percent [200 mg]) and week 148 (89.1 percent/64.4 percent [100 mg] and 88.5 percent/61.7 percent [200 mg]). [AAD 2019, abstract 10510]
At week 148, PGA response was achieved by two-thirds of participants receiving tildrakizumab 100 and 200 mg (65.1 percent and 66.4 percent, respectively).
There was a 15.5-percent discontinuation rate by week 148 primarily due to treatment withdrawal (6.0 percent) followed by AEs (2.3 percent).
AE incidence rates in reSURFACE 2 were similar to reSURFACE 1, with low cumulative numbers of patients with AEs of interest for both 100/200-mg dosages (1.2/1.3 PY for severe infections, 0.3/0.6 for confirmed extended MACE, and 0.3/0.2 for drug-related hypersensitivity reactions).
Taken together, with over 3 years of extension, the PASI and PGA response rates were considered high and durable, noted the researchers. The low AE rates suggest a lack of dose effect on safety events, they added.