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

Abstract

Summary 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), 72·6%, 53·8% and 28·9% of tildrakizumab 100‐mg responders and 80·2%, 59·9% and 32·6% 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 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient‐years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure‐adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 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. What's already known about this topic? Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short‐term use in the treatment of patients with moderate‐to‐severe plaque psoriasis. What does this study add? High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab. There is a favourable long‐term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.

<p>Tildrakizumab: An Evidence-Based Review of Its Use in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis</p>

“…Newly published results from a 3-year follow-up of reSURFACE 1 and 2 showed high levels of efficacy after treatment with tildrakizumab for up to 3 years. 27 For responders (≥ PASI75 at week 28) who remained on tildrakizumab 100 mg, approximately 73% attained PASI75 and 54% PASI90 at the end of the follow-up at week 148, and for responders who remained on 200 mg approximately 80% attained PASI75 and 60% PASI90.…”

“…Partial responders (PASI ≥50 and PASI ≤75) to tildrakizumab 200 mg continued on the same dose, while partial responders to 100 mg were rerandomized to 200 or 100 mg tildrakizumab. 27 The primary endpoint for both studies was the proportion of patients achieving at least PASI75 and PGA score of 0 or 1 with ≥2-grade score reduction from baseline at week 12. Secondary endpoints were PASI90, PASI100 at week 12, and proportion of participants with a DLQI score of 0 or 1 at week 12 and 28.…”

“…Data from a 3-year follow-up during and after treatment with tildrakizumab showed no increased risk of major cardiovascular events. 27 Other AEs of special interest were AEs associated with other types of biologics (eg serious infections, tuberculosis, malignancies, candida infection, worsening of preexisting inflammatory bowel disease, suicidal ideation and behavior), 12,41,42 and no increased rates of these AEs were seen during treatment with tildrakizumab.…”

“…Data from the long-term follow-up after 148 weeks has recently been published. 27 Safety was assessed in a pooled analysis from reSURFACE 1 and reSURFACE 2, and the most common treatment-emergent AE in all treatment groups was still nasopharyngitis. Other frequent AEs and AEs of special interest were all low and comparable across treatment groups.…”

Immunmodulatoren (Biologicals) in der Therapie von Patienten mit chronischen Dermatosen in der dermatologischen Praxis

“…Wir haben bisher im Fall der ausgeprägten mittelschweren bis schweren Plaque-Psoriasis ohne nachweisliche Gelenkbeteiligung die IL-17-Blockade (Ixekizumab, Secukinumab), die IL-17- [15,16] und der sorgfältigen Überwachung durch die Behörden weltweit hinsichtlich Arzneimittelsicherheit, ist es kaum vorstellbar, dass wir lebenslang das IL-17 oder das IL-23 blockieren. Abgesehen von den entstehenden Kosten ist das auch eine Frage der Ressourcen in der Praxis.…”