Preclinical characterisation of itacitinib, a Novel Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases

Covington M, He X, Scuron M, Li J, Collins R, Juvekar A, Shin N, Favata M, Gallagher K, Sarah S, Xue CB, Peel M, Burke K, Oliver J, Fay B, Yao W, Huang T, Scherle P, Diamond S, Newton R, Zhang Y, Smith.
European Journal of Pharmacology. 2020 Oct 15;885:173505. doi: 10.1016/j.ejphar.2020.173505

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombina...

Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis

Genovese MC, Kremer JM, van Vollenhoven RF, Alten R, Scali JJ, Kelman A, Dimonaco S, Brockwell L.
Arthritis Rheumatol. 2017 Sep;69(9):1751-1761. doi: 10.1002/art.40176

In this pooled analysis investigating liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab (TCZ) treatment for RA in clinical trials, although transaminase elevations were frequent, rates of hepatic serious AEs remained low. Data were pooled from patients who received ≥1 dose of IV TCZ with or without DMARDs in Phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study. A total of 4171 patients were included in the all-exposure populati...

Metotreksat Tedavisi Almakta Olan Aktif Romatoid Artritli Japon Hastalarda Baricitinibin Etkinliği ve Güvenliği: 12 Haftalık, Çift Kör, Randomize Plasebo Kontrollü Bir Çalışma

Tanaka Y, Emoto K, Cai Z, et al.
J Rheumatol. 2016;43(3):504–511.

Clinical trials have shown baricitinib once daily to be effective in patients with RA. However, this Janus kinase (JAK) 1/JAK2 inhibitor has not been evaluated in a Japanese population. In this 12-week, placebo-controlled study, 145 Japanese patients were enrolled and received placebo, 1 mg, 2 mg, 4 mg or 8 mg oral baricitinib daily. Efficacy results were encouraging and consistent with earlier trials. Significantly more baricitinib patients achieved ACR20 response at Week 12 of treatment compa...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Bahtiyar Toz

Aktif Romatoid Artritli Japon Hastalarda Tofacitinib’in Monoterapi Olarak Etkinliği ve Güvenliği: Bir 12-Haftalık, Randomize, Faz 2 Çalışma

Tanaka Y, Takeuchi T, Yamanaka H, Nakamura H, Toyoizumi S, Zwillich S.
Mod Rheumatol. 2014 Dec 11:1–25. [Epub ahead of print]

In Japan, the biologic DMARDs infliximab, etanercept, adalimumab, golimumab and certolizumab pegol, as well as tocilizumab and abatacept are approved for use in patients with active RA and an inadequate response to existing therapies. However, not all patients respond to these therapies adequately, creating an unmet need for therapeutic options with alternative mechanisms of action. The oral JAK inhibitor tofacitinib has demonstrated efficacy as monotherapy or in combination with DMARDs for th...

Keywords: JAK, Tofacitinib, Clinical, Phase 2

Translated by: Ege Sinan TORUN