METHODS
Study Design
The pooled efficacy analyses included all patients with a baseline PGA score of 2 or higher (mild or worse) before treatment with tapinarof cream 1% QD in the PSOARING trials. This included patients who received tapinarof cream 1% in PSOARING 1 and PSOARING 2 who may or may not have continued into PSOARING 3, as well as those who received the vehicle in PSOARING 1 and PSOARING 2 who enrolled in PSOARING 3 and had a PGA score of 2 or higher before receiving tapinarof cream 1%.
Trial Participants
Full methods, including inclusion and exclusion criteria, for the PSOARING trials have been previously reported.17,18 Patients were aged 18 to 75 years and had chronic plaque psoriasis that was stable for at least 6 months before randomization; 3% to 20% total BSA affected (excluding the scalp, palms, fingernails, toenails, and soles); and a PGA score of 2 (mild), 3 (moderate), or 4 (severe) at baseline.
The clinical trials were conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval was obtained from local ethics committees or institutional review boards at each center. All patients provided written informed consent.
Trial Treatment
In PSOARING 1 and PSOARING 2, patients were randomized (2:1) to receive tapinarof cream 1% or vehicle QD for 12 weeks. In PSOARING 3 (the long-term extension trial), patients received up to 40 weeks of open-label tapinarof, followed by 4 weeks of follow-up off treatment. Patients received intermittent or continuous treatment with tapinarof cream 1% in PSOARING 3 based on PGA score: those entering the trial with a PGA score of 1 or higher received tapinarof cream 1% until complete disease clearance was achieved (defined as a PGA score of 0 [clear]). Those entering PSOARING 3 with or achieving a PGA score of 0 (clear) discontinued treatment and were observed for the duration of maintenance of a PGA score of 0 (clear) or 1 (almost clear) while off therapy (the protocol-defined “duration of remittive effect”). If disease worsening (defined as a PGA score 2 or higher) occurred, tapinarof cream 1% was restarted and continued until a PGA score of 0 (clear) was achieved. This pattern of treatment, discontinuation on achieving a PGA score of 0 (clear), and retreatment on disease worsening continued until the end of the trial. As a result, patients in PSOARING 3 could receive tapinarof cream 1% continuously or intermittently for 40 weeks.
Outcome Measures and Statistical Analyses
The assessment of total BSA affected by plaque psoriasis is an estimate of the total extent of disease as a percentage of total skin area. In the PSOARING trials, the skin surface of one hand (palm and digits) was assumed to be approximately equivalent to 1% BSA. The total BSA affected by psoriasis was evaluated from 0% to 100%, with greater total BSA affected being an indication of more extensive disease. The BSA efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved a 1% or lower or 0.5% or lower total BSA affected. The smallest BSA affected increment that investigators were trained to measure and could record was 0.1%.
