Indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis

<jats:p>N/A</jats:p>

• Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs) and is approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • This systematic literature review (SLR) and network meta-analysis (NMA) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the Psoriasis Area and Severity Index (PASI) at Weeks 10−16, 24−28, and 44−60 • PASI 75 (75% improvement in PASI) response rate with deucravacitinib was comparable to that of first-generation biologics at Week 16, and higher at Week 24; at Week 52, it was comparable to that of the most effective fi rstgeneration biologics

Objective
• The objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis

Methods
• Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on PASI • Phase 3 trial data were included when: -Nonresponder imputation was applied 1,2 -Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis 3

Results
• The SLR identifi ed 47 phase 3 RCTs that applied nonresponder imputation and were included in the NMA (Figure 1 and Figure  aPooled analyses of RCTs were not included in the SLR unless unique data were available that were not published elsewhere. bRCTs eligible for Global PASI NMA and phase 3 global NRI PASI NMA, including POETYK PS0-1 and POETYK PSO-2. NMA, network meta-analysis; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; RCT, randomized controlled trial; SLR, systematic literature review.     Figure 3A) • PASI 75 response with deucravacitinib increased at Week 24 to 63.3% (Crl, 58.0%, 68.4%; Figure 3B) • At Week 52, the PASI 75 response rate for deucravacitinib (65.9%; Crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics -adalimumab (62.8%; Crl, 55.3%, 69.6%) and ustekinumab (68.0%; Crl, 64.6%, 71.5%; Figure 3C) • Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points  -Studies were conducted in multiple or single countries with diverse ethnic representation • NMA was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate PASI responses over short-, mid-, and long-term follow-up periods (Weeks 10−16, 24−28, and 44−60, respectively) and reported following the PRISMA Reporting Guidelines for meta-analysis 3

RCT publications and 132 pooleda analyses included in SLR
• Newer IL-17 and IL-23 inhibitors showed the highest PASI 75 response rates of the included treatments, across all time points  • The PASI 75 response rates for deucravacitinib were within the range of those for first-generation biologics at Weeks 10-16 and 24-28 • At 1 year, the PASI 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • The psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies