Artigos Científicos | 2019
Curr Pharm Des. 2019 Apr 5. doi:
10.2174/1381612825666190405141410. [Epub ahead of print]
JAK inhibition: the most promising agents in the IBD pipeline? Fernández-Clotet A, Castro-Poceiro J, Panés J.
Under current therapeutic algorithms, half of the patients with moderate-severe ulcerative colitis or Crohn's disease fail in achieving a sustained remission. New drugs with different mechanisms of action are needed. After two decades of new drug avenues in inflammatory bowel disease dominated by the development of monoclonal antibodies, in recent years we are witnessing promising developments of small molecules for these conditions. Their intrinsic characteristics make them attractive compared to monoclonal antibodies based on their oral administration, short plasma half-life, lack of immunogenicity and predictable pharmacokinetics. Among them, Janus kinase (JAK) inhibitors are a promising new class that have demonstrated efficacy with a favorable safety profile in clinical trials. Tofacitinib has been the first JAKinhibitor approved for the treatment of ulcerative colitis. This review discusses the molecular aspects of the JAK-STAT pathway, its role in the pathogenesis of inflammatory bowel disease, and the rational use of JAK inhibitors in these conditions. The different compounds with JAKinhibitory activity tested are reviewed and provide an overview of recent evidence of clinical trials. Finally, we consider the positioning of these drugs in the treatment of inflammatory bowel diseases.
Curr Pharm Des. 2019 Mar 13. doi:
10.2174/1381612825666190313140811. [Epub ahead of print]
IL-23 Blockers: Born to be First-line Biologic Agents in IBD?
Argollo MC, Allocca M, Furfaro F, Danese S.
Over the past decades, the advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD. However, primary and more importantly, secondary loss of response to anti-TNF agents, is often observed. Thus, new treatment options have been actively explored and some have already been incorporated in the current clinical practice. Among the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have been first presented, in clinical practice, by the anti-p40 mAb ustekinumab in Crohn's disease (CD). More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.