reSURFACE studies show long-term benefit of tildrakizumab in chronic plaque psoriasis

The efficacy of tildrakizumab in chronic moderate-to-severe* plaque psoriasis is maintained after 5 years of treatment, final pooled analyses of the phase III reSURFACE 1 and reSURFACE 2 trials showed.

“Tildrakizumab provided sustained long-term disease control over 5 years, based on both relative PASI responses and absolute PASI scores, in responders to tildrakizumab 100 or 200 mg and partial responders or non-responders to etanercept who switched to tildrakizumab,” presented Professor Diamant Thaçi from the University of Lübeck, Lübeck, Germany, at EADV 2020.

The trials included adults with moderate-to-severe chronic plaque psoriasis who were randomized to receive subcutaneous tildrakizumab (100 or 200 mg QW at weeks 0, 4, and every 12 weeks thereafter) or placebo, or, in reSURFACE 2, etanercept (50 mg BIW to week 12 and QW to week 28). The present analysis comprised patients in both trials with response to tildrakizumab at week 28 (PASI ≥75) who continued the same dose in part 3 and patients who were partial (PASI 50 to <75) or non-responders (PASI ≤50) to etanercept at week 28 and switched to tildrakizumab 200 mg in part 3.

A total of 302, 213, and 107 patients in the tildrakizumab 100 mg, 200 mg, and etanercept-tildrakizumab groups, respectively, continued to the extension phase, with 262, 190, and 93 completing week 244.

In patients with response to tildrakizumab 100 mg, efficacy was sustained between weeks 28 and 244 (PASI 75: 99.7 and 88.7 percent, respectively; PASI 90: 70.8 and 65.9 percent, respectively; PASI 100: 28.6 and 32.8 percent, respectively). [EADV 2020, Presentation ID D3T03.3C–3115]

Similar results were observed with tildrakizumab 200 mg, with 100 and 92.5 percent achieving PASI 75 at weeks 28 and 244, respectively, 73.1 and 69.5 percent achieving PASI 90, and 36.6 and 40.8 percent achieving PASI 100 at those respective weeks.   

Patients who switched from etanercept to tildrakizumab also showed improved efficacy at week 244, with 81.3, 49.5, and 21.5 percent achieving PASI 75, 90, and 100, respectively.

Absolute PASI scores were also sustained over 5 years among patients on tildrakizumab 100 mg, with 88.7, 78.8, and 47.7 percent achieving PASI <5, <3, and <1, respectively, at 244 weeks, from 96.4, 85.1, and 50.8 percent at week 28. Similar results were observed with tildrakizumab 200 mg (96.5, 86.8, and 55.1 percent achieving PASI <5, <3, and <1 at week 28 and 90.6, 82.6, and 57.7 percent at week 244), and etanercept-tildrakizumab (85.0, 66.4, and 36.4 percent achieving PASI <5, <3, and <1, respectively, at 244 weeks).

Over 2,688.4 and 2,753.5 patient-years (PYs) of follow-up in the tildrakizumab 100 and 200 mg groups, respectively, drug-related treatment-emergent adverse events (TEAEs) occurred at an exposure-adjusted incidence rate (EAIR) of 9.3 and 9.8 per 100 PYs. Drug-related serious AE EAIRs were 0.8 and 0.5 per 100 PYs, respectively. The death rate was 0.3 and 0.2 per 100 PYs, respectively. Drug-related AEs led to discontinuation in 0.7 and 0.3 per 100 PYs, respectively, while serious drug-related AEs led to discontinuation in 0.3 and 0.2 per 100 PYs, respectively.

Rates of TEAEs of special interest were also low and did not vary between the tildrakizumab 100 and 200 mg groups. These included severe infection (1.2 and 1.3 per 100 PYs, respectively), major adverse cardiovascular events (0.5 and 0.7 per 100 PYs), drug-related hypersensitivity (0.3 and 0.1 per 100 PYs), malignancy excluding nonmelanoma skin cancer (NMSC; 0.7 and 0.6 per 100 PYs), melanoma (0.1 per 100 PYs in both groups), and NMSC (0.4 per 100 PYs in both groups).

“The safety profile of tildrakizumab remains reassuring,” said Thaçi. “With over 5,400 PYs of combined accumulated exposure among both doses, the rates of serious AEs and AEs of special interest … were low. There were no apparent dose-dependent safety signals and no new or unexpected AEs,” he said.