Treat-to-Target Outcomes With Tapinarof Cream 1% in Phase 3 Trials for Plaque Psoriasis
The National Psoriasis Foundation (NPF) treatment targets aim to achieve 1% or lower body surface area (BSA) affected after 3 months of treatment. European psoriasis treatment guidelines aim to achieve similar goals based on improvements in Psoriasis Area and Severity Index (PASI) scores. We performed pooled analyses of the PSOARING phase 3 program, which evaluated treat-to-target outcomes for patients treated with tapinarof cream 1% once daily (QD) for up to 52 weeks. Our analyses included 915 patients from PSOARING 1 and PSOARING 2 who had Physician Global Assessment (PGA) scores of 2 or higher before undergoing treatment with tapinarof, including those who received the vehicle in PSOARING 1 and PSOARING 2 and then tapinarof in PSOARING 3. The treatment targets we analyzed included the proportion of patients achieving an absolute BSA of 1% or lower or an absolute total PASI score of 3 or lower. In total, 40% of patients achieved the stringent NPF target of BSA of 1% or lower within 3 months, and 61% achieved a BSA of 1% or lower at any time (median, ~4 months). Furthermore, 75%, 67%, and 50% achieved PASI scores of 3, 2, and 1 or lower, respectively, at any time (median, ~2–6 months). Our results indicated that a high percentage of patients with mild to severe psoriasis can achieve and exceed ambitious treatment targets when treated with topical tapinarof monotherapy for up to 1 year.
Practice Points
- In clinical practice, many patients with psoriasis do not achieve treatment targets set forth by the National Psoriasis Foundation and the European Academy of Dermatology and Venereology, and topical treatments alone generally are insufficient in achieving treatment goals for psoriasis.
- Tapinarof cream 1% is a nonsteroidal aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults; it also is being studied for the treatment of plaque psoriasis in children 2 years and older.
- Tapinarof cream 1% is an effective topical treatment option for patients with plaque psoriasis of any severity, with no limitations on treatment duration, total extent of use, or application sites, including intertriginous skin and sensitive areas.
Psoriasis Area and Severity Index scores assess both the severity and extent of psoriasis. A PASI score lower than 5 often is considered indicative of mild psoriasis, a score of 5 to 10 indicates moderate disease, and a score higher than 10 indicates severe disease.19 The maximum PASI score is 72. The PASI efficacy outcomes used in these analyses were based post hoc on the proportion of patients who achieved an absolute total PASI score of 3 or lower, 2 or lower, and 1 or lower.
Efficacy analyses were based on pooled data for all patients in the PSOARING trials who had a PGA score of 2 to 4 (mild to severe) before treatment with tapinarof cream 1% in the intention-to-treat population using observed cases. Time-to-target analyses were based on Kaplan-Meier (KM) estimates using observed cases.
Safety analyses included the incidence and frequency of adverse events and were based on all patients who received tapinarof cream 1% in the PSOARING trials.
RESULTS
Baseline Patient Demographics and Disease Characteristics
The pooled efficacy analyses included 915 eligible patients (Table). At baseline, the mean (SD) age was 50.2 (13.25) years, 58.7% were male, the mean (SD) weight was 92.2 (23.67) kg, and the mean (SD) body mass index was 31.6 (7.53) kg/m2. The percentage of patients with a PGA score of 2 (mild), 3 (moderate), or 4 (severe) was 13.9%, 78.1%, and 8.0%, respectively. The mean (SD) PASI score was 8.7 (4.23) and mean (SD) total BSA affected was 7.8% (4.98).
Efficacy
Achievement of BSA-Affected Targets—
Achievement of Absolute PASI Targets—Across the total trial period (up to 52 weeks), an absolute total PASI score of 3 or lower was achieved by 75% of patients (686/915), with a median time to achieve this of 2 months (KM estimate: 58 days [95% CI, 57-63]); approximately 67% of patients (612/915) achieved a total PASI score of 2 or lower, with a median time to achieve of 3 months (KM estimate: 87 days [95% CI, 85-110])(Figure 2; Supplementary Figures S3a and S3b). A PASI score of 1 or lower was achieved by approximately 50% of patients (460/915), with a median time to achieve of approximately 6 months (KM estimate: 185 days [95% CI, 169-218])(Figure 2, Supplementary Figure S3c).
Illustrative Case—Case photography showing the clinical response in a 63-year-old man with moderate plaque psoriasis in PSOARING 2 is shown in Figure 3. After 12 weeks of treatment with tapinarof cream 1% QD, the patient achieved all primary and secondary efficacy end points. In addition to achieving the regulatory end point of a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points, achievement of 0% total BSA affected and a total PASI score of 0 at week 12 exceeded the NPF and EADV consensus treatment targets.10,11 Targets were achieved as early as week 4, with a total BSA affected of 0.5% or lower and a total PASI score of 1 or lower, illustrated by marked skin clearing and only faint residual erythema that completely resolved at week 12, with the absence of postinflammatory hyperpigmentation.
