Data from the Swedish Rheumatology Quality Register and Swedish Registries, show a higher treatment retention and overall equivalent or better treatment response on baricitinib, compared with bDMARDs or tofacitinib, but no statistically significant differences between tofacitinib and bDMARDs.In this largest population-based study to date, comparing RA patients initiating baricitinib, tofacitinib or bDMARDs, Barbulescu, et al. help to fill some of the current knowledge gaps surrounding the effica...

February 2022

Post-hoc analysis shows that dosing up from tofacitinib 5 to 10 mg BID is associated with improved efficacy for up to 12 months, versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID is not generally associated with a significant loss of efficacy.Although clinical trials have generally shown no significant differences, in terms of efficacy and safety, when switching tofacitinib dose up or down, these per-protocol switches are not directly informative for clinical decision-making in dai...
Systematic review and network meta-analysis highlight that RA patients who receive recommended doses of the five approved JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib) are likely to experience an increase in serum low- and high-density lipoprotein (LDL and HDL) levels.JAK inhibitors have been associated with alterations in levels of LDL and HDL cholesterol, which may lead to dyslipidaemia (an important risk factor for cardiovascular disease). However, the e...
Real-world evidence finds no increased risk of CV outcomes with tofacitinib, in comparison with TNFi, in patients with RA. However, an elevated risk of CV outcomes cannot be ruled out in patients with CV risk factors or history of CVD.Recent post-marketing findings from the ‘ORAL Surveillance’ trial have raised concerns that tofacitinib, in comparison with TNFi, may increase the risk of CV disease in patients with RA who are at least 50 years of age and with at least one risk factor for CVD. To ...

Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis

N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778

In 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. ...

January 2022

This post hoc analysis provides the first detailed description of the management and outcomes of HZ events in tofacitinib RA and PsA clinical studies.While prior studies have characterised the increased HZ risk with JAKinibs, the clinical management of these events has not been detailed.To this end, Winthrop, et al. analysed data from 21 RA and 3 PsA clinical studies to evaluate how HZ events and their sequelae were clinically managed during the RA and PsA tofacitinib clinical development progra...
This post hoc analysis of pooled data from 21 clinical trials in the tofacitinib clinical trial programme highlights the importance of identifying known risk factors of RA-interstitial lung disease (ILD) in clinical practice.Citera, et al. investigated incidence rates of ILD – an extra-articular manifestation of RA – in patients with RA, receiving tofacitinib 5 or 10 mg BID and sort to identify potential risk factors for ILD in these patients....