A Systematic Literature Review and Bucher Indirect Comparison: Tildrakizumab versus Guselkumab

BACKGROUND: Psoriasis is a chronic inflammatory skin condition that impacts quality of life and requires long-term treatment and effective symptom management. Interleukin-23 (IL-23) has emerged as a key player in the pathogenesis of psoriasis and tildrakizumab and guselkumab are both immunomodulatory agents that inhibit the p19 subunit of IL-23. In its pivotal Phase III trial, tildrakizumab demonstrated greater efficacy than etanercept in moderate-to-severe psoriasis. However, there are no head-to-head trials comparing tildrakizumab with guselkumab. METHODS: We conducted a systematic literature review and Bucher indirect comparison of tildrakizumab and guselkumab, using placebo as a common comparator. We searched MEDLINE, MEDLINE In-Process, MEDLINE(R) Daily Epub Ahead of Print, and Cochrane Central Register of Controlled Trials for Phase III randomized controlled trials between 1946 and November 2018. Inclusion criteria were adult patients ≥18 years with moderate-to-severe chronic plaque psoriasis, and intervention with tildrakizumab or guselkumab compared to placebo or best supportive care. Outcomes included were severity of psoriasis as defined by the Psoriasis Area and Severity Index (PASI) 75 and PASI 90, frequency of serious adverse events (SAEs), and treatment discontinuations. Outcomes were evaluated at Weeks 12 to 16 and 24 to 28. Analysis was based on the intent-to-treat population and, for all outcomes, the number of events reported were analyzed as a proportion of the number of patients randomized to ensure consistency across trials. RESULTS: Overall, 154 unique records were identified. Five studies met the eligibility criteria and were included in the analysis; two tildrakizumab trials (reSURFACE 1 and reSURFACE 2) and three guselkumab trials (VOYAGE 1, VOYAGE 2, and a Japanese study). There was no statistically significant difference between guselkumab and tildrakizumab for PASI 75, PASI 90, SAEs, and rate of discontinuations at either timepoint. CONCLUSION: This study assessed the comparative efficacy of tildrakizumab and guselkumab for the treatment of moderate-to-severe psoriasis. Limitations included the limited number of publications, imputation of placebo arm values for Weeks 24 to 28, and limited relevance of the Japanese study. This indirect comparison does not provide evidence that one treatment is superior to the other.