Network meta-analysis of biologic treatments for psoriasis using absolute Psoriasis Area and Severity Index values ≤1, 2, 3 or 5 derived from a statistical conversion method

Abstract

Background: In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved.

Objective: Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta-analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate-to-severe psoriasis.

Methods: The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data.

Results: The ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks.

Conclusion: Data generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate-to-severe plaque psoriasis.

Figure 1

Scatter plots for derived and reported Psoriasis Area and Severity Index (PASI) 75 and PASI 90 values; derived values were estimated using the PASI conversion method.

Figure 2

Fixed‐effect model forest plots (RD and 95% CI) for absolute PASI NMAs. RD 95% CIs are only indicative and should be interpreted cautiously, as the variability coming from the estimation process of the PASI method was not incorporated. ^aThe dose of ustekinumab was based on patients' body weight: 45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg. BIW, twice weekly; CI, confidence interval; PASI, Psoriasis Area and Severity Index; Q2W, every 2 weeks; Q8W, every 8 weeks; Q12W, every 12 weeks; QM, every month; RD, risk difference.

Figure 3

Fixed‐effect model forest plots (RD and 95% CI) for relative PASI NMAs. ^aThe dose of ustekinumab was based on patients' body weight: 45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg. BIW, twice weekly; CI, confidence interval; PASI, Psoriasis Area and Severity Index; PASI 50/75/90/100, the percentage of patients achieving PASI improvement of ≥50%/75%/90%/100%; Q2W, every 2 weeks; Q8W, every 8 weeks; Q12W, every 12 weeks; QM, every month; RD, risk difference.

Figure 4

Cumulative PASI plots. ^aThe dose of ustekinumab was based on patients' body weight: 45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg. BIW, twice weekly; PASI, Psoriasis Area and Severity Index; Q2W, every 2 weeks; Q8W, every 8 weeks; Q12W, every 12 weeks; QM, every month.