BACKGROUND:

Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin.

METHODS:

We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score.

RESULTS:

In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus.

CONCLUSIONS:

Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).

Tapinarof (VTAMA®) cream 1%, a topical, non‐steroidal, aryl hydrocarbon receptor agonist, presents a valuable addition to the therapy options for topical treatment of plaque psoriasis in adults. In the pivotal 12‐week, randomized, double‐blind, vehicle‐controlled, phase 3 PSOARING 1 and PSOARING 2 trials, once‐daily tapinarof cream 1% was shown to be efficacious in reducing the severity of plaque psoriasis. Furthermore, evidence from an open‐label extension study shows that continuous and intermittent use of tapinarof cream 1% for up to 1 year has durable on‐treatment efficacy with a substantial remittive effect off treatment. Tapinarof cream 1% was generally well tolerated, with few patients discontinuing treatment in the pivotal trials due to adverse events, and with no new safety signals identified with longer‐term treatment. Post‐marketing real‐world data and/or active‐controlled studies to compare tapinarof cream 1% with other topical treatments used for plaque psoriasis would be of interest.

The purpose of this study is to assess adults with palmoplantar keratoderma (thickening skin layer on palms and soles) who are treated with the study drug, tapinarof. This is a naturally occuring compound used for the treatment of psoriasis. This study is being done to find out how well and safe this drug is for stopping or treating keratoderma. This study aims to investigate the positive impacts of daily topical Tapinarof use in the improvement of Keratoderma. Clinical efficacy and safety profile of prescribing Tapinarof for this condition will be evaluated.

INTRODUCTION:

Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.

MATERIALS AND METHODS:

This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.

RESULTS:

Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects.

DISCUSSION:

Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs.

CONCLUSION:

Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice.

This is a double-blind, randomized, vehicle controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% compared to vehicle control cream in pediatric and adult subjects with atopic dermatitis.

Tapinarof is an aromatic hydrocarbon receptor inhibitor for the treatment of adult psoriasis, and with the completion of Phase III clinical trials for this drug, it is important to understand its place among the medications used in the treatment of psoriasis for clinical application. Networks were constructed for 1% tapinarof cream with positive control (calcipotriol) and negative control (placebo). Network meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PISMA) 2015. Relevant randomized clinical trials were searched from PubMed, Cochrane Library, and National Knowledge Infrastructure (CNKI) as of February 2023. Data were analyzed using the gemtc package in R software (RStudio) to evaluate the efficacy and safety of 1% tapinarof cream in the treatment of psoriasis in adults. A total of 2408 patients were enrolled in 8 clinical studies of 1% tapinarof cream, and 6874 patients were enrolled in 14 clinial studies of calciptriol. 1% tapinarof cream was superior to placebo [OR: 8.3 (5.5, 13.0), 8.3 (5.9, 13.0), 7.3 (5.1, 11.0)] and calcipotriol in the treatment of psoriasis at 4, 8, and 12 weeks, and the incidence of adverse events was higher than that with placebo [OR: 3.3 (2.6, 4.3)] and calcipotriol, with no serious systemic adverse events. 1% tapinarof cream is a safe and effective treatment for psoriasis.

This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in adults with plaque psoriasis. Subjects in this study completed treatment in 1 of 2 Phase 3 pivotal efficacy and safety studies (Study DMVT-505-3001 or Study DMVT-505-3002). This study will consist of up to 40 weeks of treatment and a 4-week safety follow-up period.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator’s Global Assessment (IGA) achieving “clear” or “almost clear,” with 2 points or more improvement from baseline at the end of treatment, referred to as “IGA success.” For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of “IGA success” at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28–23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46–3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75–9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving “IGA success” in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

This is an open-label, multicenter study to evaluate the systemic exposure and safety of topical tapinarof cream, 1% under conditions of maximal use in adults with plaque psoriasis.

This is an open-label, long-term multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in subjects with atopic dermatitis. Subjects in this study have completed treatment in one of two Phase 3 pivotal studies (DMVT-505-3101 or DMVT-505-3102) or completed treatment in the DMVT-505-2104 study, or directly enrolled into this study. This study will consist of up to 48 weeks of treatment and a 1 week safety follow-up period.