Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

Abstract

Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate estimates at week 12 are 62.9% (95% CrI 42.5–79.9%) for abrocitinib 200 mg and 43.0% (95% CrI 24.8–64.0%) for abrocitinib 100 mg. Abrocitinib has shown a faster effect than dupilumab as regards early alleviation of itch. Because of the incomplete target selectivity of JAK inhibitors, when abrocitinib treatment is considered, laboratory screening is necessary, latent tuberculosis must be screened for, active infections are a contraindication, and special caution must be exerted in treating elderly patients and those predisposed to thromboembolic events. Even though recent meta-analyses of clinical trials have not shown that atopic dermatitis, or its treatment with JAK inhibitors or dupilumab, modify the risk of deep venous thrombosis or pulmonary embolism, long-term follow-up studies will better define the safety profile of abrocitinib.

Platelet-derived extracellular vesicles for drug delivery

“…16 CD41 and P-selectin have been identified on most PEV surfaces. 33 Phosphatidylserine could be found on some PEV surfaces. 34 Platelets also package mRNAs and non-coding RNAs inside PEVs to interact with other cells.…”

“…99 Actively, because of the expression of P-selectin on the surface of PEVs and P-selectin ligands (PSGL) on the surface of tumor cells, PEVs were confirmed to selectively bind towards tumor cells instead of other normal cells. 33 Loading with paclitaxel, PEVs could success-Fig. 4 The schematic of utilizing PEVs as a drug delivery platform for tumor diseases.…”

“…Biomaterials Science fully inhibit the invasion of various tumor cells in vitro, including breast cancer cells, and reduce the toxicity of these two chemotherapeutic drugs to normal cells. 33 Apart from paclitaxel, doxorubicin (DOX) is another widely utilized chemotherapeutic drug in clinical. 100 DOXIL, the first nano drug based on doxorubicin encapsulated in liposomes, was first on the market in 1995.…”

Structure‐guided design of potent JAK1‐selective inhibitors based on 4‐amino‐7H‐pyrrolo[2,3‐d]pyrimidine with anti‐inflammatory efficacy

“…Among them, abrocitinib, a remarkable oral JAK1‐selective inhibitor developed by Pfizer, has been applied in many countries for the treatment of patients with moderate‐to‐severe AD. [ 20 ]…”

“…Among them, abrocitinib, a remarkable oral JAK1-selective inhibitor developed by Pfizer, has been applied in many countries for the treatment of patients with moderate-to-severe AD. [20] In our previous work to develop JAK inhibitors, JA 4 (Figure 2) as a hit was validated to possess considerable anti-inflammatory activity. [21] However, poor JAK1 selectivity motivated us to optimize the structure continuously.…”