Comparison of Biologics and Oral Treatments for Plaque Psoriasis

Abstract

The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.OBJECTIVE To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.DATA SOURCES A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.STUDY SELECTION Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.DATA EXTRACTION AND SYNTHESIS Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis. PASI 75,90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline. MAIN OUTCOMES AND MEASURES RESULTSSixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses. CONCLUSIONS AND RELEVANCEThis study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.

Risankizumab: A Review in Moderate to Severe Plaque Psoriasis

“…A number of systematic reviews and network meta-analyses have indirectly compared the efficacy and safety of biological agents in patients with plaque psoriasis [ 35 – 42 ]. Generally, IL-17 inhibitors (e.g.…”

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

“…In previous meta-analyses, tildrakizumab seems to be the least efficacious IL-23p19 inhibitors. 11,34,35 Even though all of the three IL-23p19 inhibitors are high-affinity monoclonal antibodies, tildrakizumab demonstrated the weakest affinity, which may be the reason for the lower efficacy (Table 1). One would therefore expect a higher effect of 200 mg than of 100 mg, and even though the phase IIb trial and the pooled pharmacokinetic analysis supports this theory, a dosedependent efficacy could not be seen in the two phase III trials.…”

“…Similar results were seen in another recent and comprehensive meta-analyses and systematic review from Armstrong et al, comparing treatments for moderate-to-severe plaque psoriasis. 35 Brodalumab, guselkumab, ixekizumab, and risankizumab were associated with the highest rate of PASI90, both in the short and long term. A single systematic review and meta-analysis from Xu et al claimed that guselkumab was the most efficient treatment of the three IL-23p19 inhibitors.…”

“…Dose adjustment analysis revealed that patients who were responders to tildrakizumab 200 mg at week 28, and were re-randomized to tildrakizumab 100 mg, experienced little impact of efficacy demonstrated by the proportion of PASI75 responders that remained consistent throughout week 52. Partial responders to tildrakizumab 100 mg that were re-randomized to 200 mg at week 28, continued to improve but without meaningful difference compared to those who continued the dosage of 100 mg. 32 Several new systematic reviews and meta-analyses comparing the efficacy of biologics, conventional systemic therapies, and placebo, showing that biologics outperform placebo 33,34 and conventional systemic therapies, 11,35 have been published in recent years. New generation biologics (anti-IL-17 and anti-IL-23 therapies) have shown better efficacy than the first biologics registered for treatment for psoriasis.…”

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

“…We show that the appropriate usage of Biologicals is a decision with significant influence on the entire practice and the team. [2][3][4]. Vielmehr wollen wir darstellen, was es heißt, Biologicals unter den Bedingungen des Alltags in einer dermatologischen GKV-Praxis zu verordnen und die Therapie zu managen.…”