(130 days). For patients entering the trial with PGA=0 (n=79), the median duration of remittive effect off treatment was also approximately 4 months (115 days). Durability of response on treatment (ie, no tachyphylaxis) of up to 52 weeks was observed. Treatment with tapinarof cream in PSOARING 1 and 2 resulted in rapid, clinically meaningful, and statistically significant improvements in patient-reported outcomes. This included itch as measured by the Peak Pruritus Numerical Rating Scale, quality of life measured by the Dermatology Life Quality Index (DLQI), and psoriasis symptoms and functional health measured by Psoriasis Symptom Diary scores.32 Continued and durable improvement in quality of life (DLQI) was demonstrated in PSOARING 3.33
Safety and Tolerability of Tapinarof Cream in Psoriasis
Tapinarof cream 1% QD was well tolerated with long-term use up to 52 weeks as reported by patients and investigators, including when applied to sensitive and intertriginous skin areas.27
Tapinarof cream 1% QD was well tolerated with long-term use up to 52 weeks as reported by patients and investigators, including when applied to sensitive and intertriginous skin areas.27
Most treatment-emergent AEs in PSOARING 1 and 2 were mild or moderate in severity and did not lead to trial discontinuation.22 The most common treatment-emergent AEs overall were folliculitis, nasopharyngitis, and contact dermatitis.22 AEs of special interest, identified from phase 2 trials, were folliculitis, contact dermatitis, and headache, which were mostly mild or moderate. Tapinarof has a role in regulating skin barrier protein expression; consequently, tapinarof-induced folliculitis may involve follicular cornification and plugging following upregulation of components of the stratum corneum associated with keratinocyte differentiation.24,34 Therefore, folliculitis may be an ‘on-target’ effect of topical tapinarof, is generally mild and self-limiting, and does not interfere with therapy.35 There was only one severe (grade 3) event each of folliculitis, contact dermatitis, and headache occurring across the phase 3 PSOARING program with up to 52 weeks of treatment. Trial discontinuation rates due to AEs of special interest were low in PSOARING 1 and 2 (≤1.8%, ≤2.0%, and ≤0.6% for folliculitis, contact dermatitis, and headache, respectively) and PSOARING 3 (1.2%, 1.4%, and 0%, respectively).22,27
Patient Satisfaction with Tapinarof Cream for Psoriasis
In PSOARING 3, patient satisfaction with efficacy, formulation elegance, application ease, impact on daily life, and preference for tapinarof vs prior therapies was assessed at week 40 (or early termination) using a Patient Satisfaction Questionnaire®.36 Most patients either strongly agreed or agreed that they could easily manage their psoriasis with tapinarof (85.8%), were satisfied with how well tapinarof worked (83.6%), felt that tapinarof cleared their skin and prevented psoriasis from returning (62.9%), had confidence in tapinarof (84.1%), would recommend tapinarof to other patients with psoriasis (84.0%), and would use tapinarof again or continue tapinarof if it was available (82.5%). Most patients were satisfied with the time spent applying tapinarof (93.2%) and felt that tapinarof was easy to apply (96.3%), was quickly absorbed (89.5%), felt good on their skin (79.9%), was not greasy (89.0%), and were satisfied with the look and feel of tapinarof (87.7%). In patients who had previously used other topical agents and those who had used systemic drugs, the majority considered tapinarof more effective, easier to use, and preferred versus previous agents.
Clinical Use of Tapinarof Cream to Treat Plaque Psoriasis Patients should be advised to apply tapinarof cream as a thin layer once daily to affected areas.37 Tapinarof cream has no warnings, restrictions on location of application or duration of use, precautions, contraindications, or drug interactions; it is not for oral, ophthalmic, or intravaginal use.37 Pharmacokinetic evaluation of topical tapinarof in patients with psoriasis has demonstrated minimal systemic exposure, which supports the absence of restrictions and of drug–drug interactions.24,34,37
CONCLUSION
Tapinarof cream 1% QD is a novel, non-steroidal topical treatment that binds to a distinct site on AhR, creating unique biological outcomes that manifest clinically as therapeutic disease control for patients with psoriasis. The proposed mechanism of action includes decreasing pro-inflammatory cytokines, decreasing oxidative stress, and promoting skin barrier normalization. The remittive effect demonstrated in the long-term extension trial may be attributed to the additional roles of AhR in modulating T-cell responses that are a major component of psoriatic lesions.38
Tapinarof cream was efficacious and well tolerated in adult patients with mild, moderate, or severe plaque psoriasis, including on sensitive and intertriginous skin areas, and demonstrated an approximately 4-month remittive effect off therapy and no tachyphylaxis on therapy with long-term use. The most common AE was folliculitis, which was mostly mild or moderate in severity, likely representing an ‘on target’ effect of tapinarof, and resulted in few trial discontinuations. Tapinarof cream 1% QD is a new topical treatment indicated for patients with plaque psoriasis with no restrictions regarding duration of use, application site, concomitant therapies, and extent of body surface area affected.
DISCLOSURES
Margaret Bobonich has served as a speaker and/or consul-tant for AbbVie, Boehringer Ingelheim, Biofrontera, Bristol Myers Squibb, Dermavant Sciences, Inc., Eli Lilly, Novartis, and UCB Biopharma.
Joe Gorelick has served as a consultant and/or speaker for AbbVie, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharmaceuticals, and UCB Biopharma.
