TYK2 Inhibitor for the Treatment of Plaque Psoriasis

plaque psoriasis on chest
plaque psoriasis on chest
The efficacy and safety of a once daily oral tyrosine kinase 2 (TYK2) inhibitor for the treatment of plaque psoriasis is assessed.

A phase 2b clinical trial found that a once daily oral tyrosine kinase 2 (TYK2) inhibitor was effective and well tolerated at 40 weeks for the treatment of moderate to severe plaque psoriasis. These findings were published in Journal of the American Academy of Dermatology.

This randomized, double-blind, placebo-controlled, parallel-group study (Clinical Trial: NCT03895372/EudraCT 2018-004669-16).was conducted at 36 sites in Canada, the United States, Poland, and Japan in 2019 and 2020. Patients (N=178) with moderate to severe plaque psoriasis were randomly assigned in a 1:1:2:2:2 ratio to receive 50 mg (n=22), 100 mg (n=23), 200 mg (n=45), 400 mg (n=43) daily oral PF-06826647, or placebo (n=45) for 16 weeks. After the placebo-controlled investigational treatment period, patients entered a 24-week nonplacebo-controlled extension, and a 4-week follow-up. The primary efficacy endpoint was the percentage of patients achieving 90% or greater Psoriasis Area and Severity Index (PASI) improvement at week 16.

The study population comprised 68.5% men, mean age, 44.8 (standard deviation [SD], 12.7) years, 88.8% were White, and baseline PASI score was 23.0 (SD, 10.5) points.

At week 16, 33.0% of the 200 mg (P =.0004) and 46.5% of the 400 mg (P <.001) recipients achieved PASI 90, which was significantly higher than placebo recipients. Similarly, more of the 200 mg and 400 mg recipients achieved 75% PASI improvement compared with placebo (both P <.05).

Between baseline and week 16, 25 patients discontinued treatment, 9 of whom endorsed treatment-emergent adverse events (TEAE) as the motivation for discontinuation. Between weeks 16 and 40, 23 participants discontinued, 9 of whom endorsed TEAEs.

TEAEs occurred among 51.1% of the placebo recipients, 59.1% of the 50 mg, 69.6% of the 100 mg, 62.2% of the 200 mg, and 67.4% of the 400 mg PF-06826647 recipients. Severe TEAEs were observed among more of the 100 mg group (39.1%) compared with other doses (range, 13.6%-20.9%) or placebo (17.8%).

The most common abnormal laboratory levels were increased blood creatine phosphokinase (n=32), low total neutrophil count (n=10), high total neutrophil count (n=9), and low hemoglobin (n=5). Most abnormal laboratory events were observed in the intervention study arms.

This study was biased by the lack of patient diversity and these findings may not be generalizable among a more diverse patient population, the researchers noted.

This study found that 200 and 400 mg daily PF-06826647 was associated with greater percentage of PASI 90 at week 16 compared with placebo. PF-06826647 was well tolerated up to week 40.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures. The study was funded by Pfizer.


Tehlirian C, Singh RSP, Pradhan V,e t al. Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2022;S0190-9622(22)00552-7. doi:10.1016/j.jaad.2022.03.059