Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks

Background Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. Objectives To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. Methods Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (>= 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). Results At week 148 (NRI), 72 center dot 6%, 53 center dot 8% and 28 center dot 9% of tildrakizumab 100-mg responders and 80 center dot 2%, 59 center dot 9% and 32 center dot 6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32 center dot 5%, 25 center dot 0% and 10 center dot 0%; and 47 center dot 1%, 27 center dot 5% and 12 center dot 8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66 center dot 9%, 43 center dot 8% and 14 center dot 9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1 center dot 7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1 center dot 2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5 center dot 9 per 100 PYs; 5 center dot 5 per 100 PYs), severe infections (1 center dot 1 per 100 PYs; 1 center dot 1 per 100 PYs), malignancies (0 center dot 6 per 100 PYs; 0 center dot 4 per 100 PYs) and major adverse cardiovascular events (0 center dot 4 per 100 PYs; 0 center dot 5 per 100 PYs) were low. Conclusions Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.