Immunotherapy. 2022 doi: 10.2217/imt-2022-0109
Deucravacitinib demonstrates promising results as a TYK2-specific immunotherapy and shows considerable efficacy yet is able to avoid the side effect profile observed with other JAK inhibitors.
Toxicity Signals Associated with Secukinumab: A Pharmacovigilance Study Based on The United States Food And Drug Administration Adverse Event Reporting System Database
Br J Clin Pharmacol. 2022 doi: 10.1111/bcp.15535
This study explored the clinical characteristics, outcomes, and time to onset of the four main toxicities of secukinumab with hypersensitivity identified as the most common toxicity.
Venous Thromboembolism with JAK Inhibitors and Other Immune-Modulatory Drugs: a Swedish Comparative Safety Study Among Patients with Rheumatoid Arthritis
Ann Rheum Dis. 2022. doi: 10.1136/ard-2022-223050
Nationwide register-based study in Sweden finds that patients with RA treated with JAKinibs in routine clinical practice are at increased risk of venous thromboembolism (VTE), compared with those treated with bDMARDs, an increase numerically confined to pulmonary embolism.
Expert Opin Drug Saf. 2022. doi: 10.1080/14740338.2022.2100343
It is too early to conclude that the second-generation JAK inhibitors have a lower VTE risk and caution in patients with VTE risk factors is required.
N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778In this paper, Ytterberg et al. compare incidence of MACE and cancers (excluding NMSC) with tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi. They found that risk of MACE and cancer were higher with tofacitinib versus TNFi, and did not meet noninferiority criteria.This prospective head-to-head safety trial compared tofacitinib to TNFi, and was required by the FDA after increases in lipid levels and cancers were observed during tofacitinib drug development. ...
Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-naïve Patients with Moderately to Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Randomized, Double-blind, Active-comparator, Multi-center, Multi-country Trial
Arthritis Rheumatol 2020Upadacitinib monotherapy demonstrated superior clinical, radiographic, and patient-reported outcomes versus methotrexate in methotrexate-naïve RA patients.This 48-week double-blind active comparator study investigated upadacitinib monotherapy in patients with early RA, who were either methotrexate-naïve, or who had very limited exposure. 947 patients were randomised to once-daily upadacitinib 15 or 30 mg, or weekly methotrexate. Unusually, there were two separate primary endpoints, selected for ...
Impact of Janus Kinase Inhibitors on Risk of Cardiovascular Events in Patients with Rheumatoid Arthritis: Systematic Review and Meta-Analysis of Randomised Controlled Trials
Ann Rheum Dis. 2019 Aug;78(8):1048-1054.Existing evidence from RCTs indicated no significant change in CV risk for JAK inhibitor (JAKinib) treated RA patients in a short-term perspective compared to placebo.Patients with RA have an elevated risk of CV morbidity and mortality, which cannot be fully explained by traditional CV risk factors. Reaching remission or LDA in order to reduce CV events (CVE) is encouraged in the current EULAR recommendations. JAKinibs and their roles in the modulation of CV risk remain undetermined. This study ...
Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors
Drug Saf 2018 Apr; 41(4):357–61 DOI: 10.1007/s40264-017-0622-2Thromboembolic-related adverse events (AEs) were, in general, not considered a class-wide safety concern after analysis of tofacitinib (TOF) and ruxolitinib (RUX) clinical data, though pulmonary thrombosis is considered a potential class-wide safety issue and portal vein thrombosis was considered a potential safety issue for RUX. During analysis of baricitinib (BARI) clinical trial data, the FDA expressed concerns regarding thromboembolic events. Following this, the CHMP have recently added a pr...
Lipid profile changes in patients with chronic inflammatory arthritis treated with biologics and tofacitinib in randomized clinical trials: A systematic review and meta-analysis
Arthritis Rheumatol. 2015;67(1):117–127Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials.
Basic Clin Pharmacol Toxicol. 2013 Oct 24. doi: 10.1111/bcpt.12164The inhibition of the JAK/STAT pathway has proven to be a powerful therapeutic tool in the treatment of autoimmune diseases. The authors review the role of the JAK/STAT pathway in human disease, including the role of mutations in defective function of this pathway. They discuss the rationale behind JAK inhibition and review the two JAK inhibitors currently approved by the FDA for clinical use; tofacitinib, for the treatment of RA, and ruxolitinib, for the treatment of polycythaemia vera and myel...