The challenge

Comparing the effectiveness of treatments for moderate-to-severe plaque psoriasis requires overcoming the following challenges:

‍(1) Although the majority of patients require long-term treatment, most trials investigate the initial “induction phase” of treatment, during the first 10-16 weeks.

‍(2) The relatively few studies with long-term evidence during the “maintenance phase” of treatment differ substantially in design (e.g. cross-over, withdrawal, re-treatment) and treatments compared.

We wanted to find a scientifically rigorous way to identify all systemic therapies approved for this indication and to compare their efficacy at one year based on the gold-standard Psoriasis Area and Severity Index (PASI).

The approach

Building on our previous work, which we published in a high-impact journal and has been cited over 50 times, we identified, synthesised, and analysed studies published between 2000 and 2018 according to PRISMA guidelines. We comprehensively assessed the studies for heterogeneity that might confound our comparisons. This led us to perform a hierarchical Bayesian network meta-analysis of PASI using an ordered probit model to estimate probabilities that patients would achieve PASI scores of 75, 90 or 100.

Using this thorough review, we arrived at two clarifying discoveries. One was that placebo cross-over after the induction phase turned many studies into essentially one-arm trials. The other was that PASI in the placebo group appeared to plateau in the transition from the induction to maintenance phase of treatment. This led us to propose two analyses, which we validated with leading psoriasis clinicians:

(1) One analysis would compare outcomes at 52 weeks across 9 studies that reported complete placebo and treatment data out to that time point.

(2) A second analysis would assume that placebo response during a maintenance phase would remain the same as during the induction phase. This assumption of a “placebo plateau” allowed us to compare placebo and treatment data out to 52 weeks in a network of 28 studies, instead of 9.

The outcome

Our work provided a rigorous foundation for our clients to compare their product with all available treatments for moderate-to-severe plaque psoriasis, and these comparisons could support major R&D decisions. The work was subsequently published in three highly ranked journals and presented at a major international meeting. Our work has proven extremely relevant to researchers, clinicians and regulators: the Professional Society for Health Economics and Outcomes Research (ISPOR) commended our approach in 2020, creating an industry-wide precedent for how healthcare stakeholders can overcome evidence gaps that interfere with health economics and outcomes research.