|
KMID : 1149120180150020029
|
|
Journal of the Korean Society for Psoriasis
2018 Volume.15 No. 2 p.29 ~ p.34
|
|
|
Small molecule inhibitors in psoriasis
|
|
Byun Ji-Yeon
|
|
|
Abstract
|
|
|
|
Even though the recent advance in biologic therapy for psoriasis, there is still an unmet need for oral medications that can be administered long-term with favorable tolerability and safety. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and show potential to treat inflammatory skin diseases. Presently, small molecules available for psoriasis are phosphodiesterase (PDE) 4 inhibitors and Janus Kinase (JAK) inhibitors. Apremilast, an oral PDE4 inhibitor, was approved by United States Food and Drug Administration in 2014 for psoriatic arthritis and psoriasis and also approved by Korea Food & Drug Administration in 2017. From several randomized controlled trials (RCTs), apremilast has demonstrated efficacy in patients with moderate to severe plaque psoriasis (28.8~39.8% of PASI75) at week 16. Most common adverse events of apremilast were diarrhea, nausea, and weight loss. Tofacitinib, a JAK1/3 inhibitor, was recently approved in several countries for the treatment of rheumatoid arthritis, but not for psoriasis. However, it is still under active investigation for psoriasis. From multiple global phase III RCTs, PASI 75 responses at week 12~24 were 33.5~46.0% with tofacitinib 5 mg bid and 55.2%~63.6% with 10 mg bid. Common adverse effects include nasopharyngitis, upper respiratory infection, and headache. Dose dependent laboratory abnormalities involving cytopenia, increased CPK and cholesterol and transaminitis can be observed. The clinical and safety evidence of PDE4 inhibitor, apremilast, and JAK inhibitors are reviewed here.
|
|
|
KEYWORD
|
|
|
Janus kinase inhibitors, Phosphodiesterase 4 inhibitors, Psoriasis, Small molecules
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|