PSOARING trials boost potential of tapinarof for plaque psoriasis

The nonsteroidal topical aryl hydrocarbon receptor (AHR)-modulating agent tapinarof 1% trumped a vehicle control cream in reducing the severity and manifestations of plaque psoriasis, according to the phase III PSOARING 1 and 2 trials.

Despite currently available systemic and biologic therapies for moderate-to-severe psoriasis, topical agents remain the mainstay of treatment for most patients. [J Am Acad Dermatol 2021;84:432-470; J Am Acad Dermatol 2019;80:1029-1072] However, topical regimens are tied to poor treatment adherence and low patient satisfaction owing to application issues and drug properties. [Actas Dermosifiliogr 2013;104:488-496; Patient Prefer Adherence 2016;10:2357-2367; Semin Cutan Med Surg 2016;35:S36-S44]

“[Moreover,] although existing topical therapies, including glucocorticoids, are efficacious especially in the short-term treatment of localized disease, some medications in this class have restrictions relating to duration and extent of use and application sites,” said the researchers.

“AHR is a ligand-dependent transcription factor with roles in the regulation of cytokine and skin barrier-protein expression and antioxidant activity, which makes it a reasonable therapeutic target for the treatment of inflammatory skin diseases and potentially other immunologic diseases,” they continued. [Int J Mol Sci 2019;20:5424; J Biol Chem 2017;292:12383-12389; J Invest Dermatol 2017;137:2110-2119]

The identical PSOARING 1 and 2 trials included 1,025 individuals (n=510 and 515, respectively) with a clinical diagnosis of chronic mild-to-severe plaque psoriasis who had stable disease for at least 6 months prior to the studies. Participants were randomized 2:1 to use tapinarof 1% cream or a vehicle cream QD for 12 weeks. [N Engl J Med 2021;385:2219-2229]

At week 12, compared with those on the vehicle cream, more patients on tapinarof achieved the primary efficacy endpoint of Physician’s Global Assessment (PGA) response, both in PSOARING 1 (35 percent vs 6 percent; relative rate [RR], 5.8) and PSOARING 2 (40 percent vs 6 percent; RR, 6.1; p<0.001 for both).

“Results for the secondary endpoints … were generally in the same direction as those for the primary endpoint,” said the researchers. These pertained to the proportion of patients achieving PASI 75* (36 percent vs 10 percent; RR, 2.8 [PSOARING 1] and 48 percent vs 7 percent; RR, 6.5 [PSOARING 2]), PASI 90* (19 percent vs 2 percent; RR, 8.5 and 21 percent vs 2 percent; RR, 7.2), and PGA score of 0/1 (38 percent vs 10 percent; RR, 2.7 and 44 percent vs 8 percent; RR, 4.6), as well as mean changes in the percentage of total body surface area (BSA) affected by psoriasis (–3.5 vs –0.2 percentage points and –4.2 vs 0.1 percentage points; p<0.001 for all).

In terms of safety and tolerability however, compared with the vehicle cream, tapinarof use was associated with higher incidences of folliculitis (24 percent vs 1 percent [PSOARING 1] and 18 percent vs 0.6 percent [PSOARING 2]), contact dermatitis (5 percent vs 0.6 percent and 6 percent vs 0 percent), and headache (4 percent vs 2 percent and 4 percent vs 0.6 percent).

Furthermore, the rates of any adverse events (AEs) were twice as high in the tapinarof vs the vehicle arm in both PSOARING 1 (50 percent vs 22 percent) and PSOARING 2 (54 percent vs 26 percent), but there were no serious AEs reported which were deemed related to either agent in either trial.

The findings align with the results of other phase II trials on tapinarof. [J Am Acad Dermatol 2019;80:714-721; J Am Acad Dermatol 2021;84:624-631] “[However, the results] may not be generalizable to other populations or … to the full spectrum of the severity of plaque psoriasis,” the researchers noted, due to the exclusion of patients with very limited or very extensive BSAs affected by psoriasis and having patients from the US and Canada only.

The researchers thus called for larger studies with longer durations to validate the findings and compare the potential of tapinarof cream against existing psoriasis treatments.