tofacitinib and Dyslipidemias

Janus kinase (JAK) inhibitors have emerged as a novel orally administered small-molecule therapy for the treatment of ulcerative colitis and possibly Crohn disease. These molecules are designed to selectively target the activity of specific JAKs and to offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease.

Topics: Animals; Dyslipidemias; Humans; Inflammatory Bowel Diseases; Janus Kinases; Opportunistic Infections; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Signal Transduction

Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis.. We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis.. Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib.. Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years.. There was relatively short follow-up time for patients who had MACEs.. While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low.

Topics: Adult; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Comorbidity; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Male; Metabolic Syndrome; Middle Aged; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Risk Factors; Treatment Outcome; Triglycerides