Sustained and improved efficacy of tildrakizumab from Week 28 to Week 52 in treating moderate-to-severe plaque psoriasis
Presenters: Elewski B1, Menter M2, Crowley J3, Tyring J4, Zhao Y5, Lowry S5, Rozzo S5, Mendelsohn A5, Parno J5, Gordon K6
Affiliations: 1Department of Dermatology, The University of Alabama at Birmingham, Birmingham, AL; 2Division of Dermatology, Baylor University Medical Center, Dallas, TX; 3Bakersfield Dermatology, Bakersfield, CA; 4Department of Dermatology, University of Texas Health Science Center, Houston, TX; 5Sun Pharmaceuticals, Princeton, NJ; 6Medical College of Wisconsin, Milwaukee, WI
Introduction: Two Phase III, double-blind, randomized controlled trials (reSURFACE 1: NCT01722331; reSURFACE 2: NCT01729754) have demonstrated efficacy and safety of tildrakizumab, a high affinity, humanized, IgG1 ?, anti-interleukin-23 monoclonal antibody, in the treatment of adult patients with moderate-to-severe plaque psoriasis over 28 weeks. This analysis evaluated longer-term data from these two trials to examine whether the efficacy is sustained or improved from Week 28 to Week 52.
Methods: Both trials randomized adult patients with moderate-to-severe plaque psoriasis to receive tildrakizumab 100mg or 200mg at Weeks 0 and 4, then every 12 weeks after Week 4. At Week 28, patients with a Psoriasis Area and Severity Index (PASI) response of at least 50 percent were re-randomized, based on their Week 28 PASI response, to receive a higher dose, a lower dose, or an unchanged dose of tildrakizumab or placebo (randomized withdrawal in reSURFACE 1 per the trial designs). The current analysis evaluated only patients treated with the same dose of tildrakizumab (100mg or 200mg) throughout the first 52 weeks. Four mutually exclusive groups were created based on Week 28 PASI response: PASI 100, PASI 90–99, PASI 75–89 and PASI 50–74. PASI responses at Week 52 (observed data) were analyzed for each Week 28 PASI-response group.
Results: This analysis included 352 patients on tildrakizumab 100mg (men: 69.9%; mean baseline age: 44.9 years) and 313 on tildrakizumab 200mg (men: 67.1%; mean baseline age: 46.4 years). The proportions of patients achieving PASI 100, PASI 90–99, PASI 75–89 and PASI 50–74 at Week 28 were 25.9 percent, 38.4 percent, 25.3 percent, and 10.5 percent, respectively, for those on the 100mg dose, and 24.6 percent, 24.3 percent, 19.5 percent and 31.6 percent, respectively, for those on the 200mg dose. Among patients who achieved Week 28 PASI of at least 90 with either dose of tildrakizumab, 88.9 to 89.4 percent maintained PASI of at least 90 at Week 52. Overall, 91.1 percent of patients on the 100mg dose and 93.9 percent on the 200mg dose with Week 28 PASI of at least 75 maintained PASI of at least 75 at Week 52. In addition, 39.3 to 40.4 percent of patients with Week 28 PASI 75 to 89 remained PASI 75 to 89 at Week 52 and 33.7 to 41.0 percent improved to PASI of at least 90. Among patients with Week 28 PASI 50 to 74, 20.2 to 29.7 percent achieved PASI of at least 90 and 52.5 to 64.9 percent achieved PASI of at least 75 at Week 52. Overall, only 2.6 percent of patients on the 100mg (n=9/352) or 200mg (n=8/313) dose had Week 52 PASI less than 50.
Conclusion: Among patients with moderate-to-severe plaque psoriasis treated with tildrakizumab 100mg or 200mg at Weeks 0 and 4, then every 12 weeks after Week 4, those who achieved Week 28 PASI of at least 50 and continued on the same dose had sustained or improved efficacy from Week 28 to Week 52. The majority patients who achieved Week 28 PASI of at least 75 or 90 maintained PASI 75 or 90 at Week 52. More than half of partial responders (PASI 50–74) at Week 28 eventually achieved PASI of at least 75 and at least one in five achieved PASI of at least 90 at Week 52.