Publications

Oral surveillance and JAK inhibitor safety: the theory of relativity

Nat Rev Rheumatol. 2022. Epub ahead of print doi: 10.1038/s41584-022-00767-7

Winthrop KL,

Cohen SB.

Putting the data into context, Winthrop, et al. conclude that the ORAL Surveillance data are not dissimilar to those from the original developmental programme, which suggested additional safety concerns at the 10 mg dosage and that resulted in the 5 mg twice daily dosage as the approved dose for RA.Following the recent results of the ORAL Surveillance (ORALSURV) study, and the consequent changes to the utilisation of JAKinibs, made by the regulatory authorities, Winthrop, et al. aim to put the O...

Keywords:

• JAK,
• Tofacitinib,
• Safety

Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data

Rheumatology (Oxford). 2022. Epub ahead of print doi: 10.1093/rheumatology/keac068

Barbulescu A,

Askling J,

Chatzidionysiou K,

Forsblad-d'Elia H,

Kastbom A,

Lindström U,

Turesson C,

Frisell T

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...

Keywords:

• JAK,
• Baricitinib,
• Real-World,
• Efficacy

Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)

Clin Rheumatol. 2022 Jan 1. Epub ahead of print doi: 10.1007/s10067-021-05908-z

Mueller RB,

Schulze-Koops H,

Furst DE,

Cohen SB,

Kwok K,

Wang L,

Killeen T,

von Kempis J

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...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• Dosing

Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis

Clin Rheumatol. 2022. Epub ahead of print doi: 10.1007/s10067-021-06003-z

Li N,

Gou ZP,

Du SQ,

Zhu XH,

Lin H,

Liang XF,

Wang YS,

Feng P.

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...

Keywords:

• JAK,
• Meta analysis,
• Review

Tofacitinib and risk of cardiovascular outcomes: results from the Safety of Tofacitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study

Ann Rheum Dis. 2022 Jan 13. Epub ahead of print doi: 10.1136/annrheumdis-2021-221915

Khosrow-Khavar F,

Kim SC,

Lee H,

Lee SB,

Desai RJ

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 ...

Keywords:

• JAK,
• Tofacitinib,
• Real-World,
• Cardiovascular

Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis

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

Ytterberg SR,

Bhatt DL,

Mikuls TR,

Koch GG,

Fleischmann R,

Rivas JL,

Germino R,

Menon S,

Sun Y,

Wang C,

Shapiro AB,

Kanik KS,

Connell CA

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. ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy,
• Cardiovascular

Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment

Rheumatol Ther. 2021. Epub ahead of print. doi: 10.1007/s40744-021-00390-0

Winthrop KL,

Curtis JR,

Yamaoka K,

Lee EB,

Hirose T,

Rivas JL,

Kwok K,

Burmester GR

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...

Keywords:

• JAK,
• Tildrakizumab,
• Safety,
• Infections

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients

J Clin Rheumatol. 2021;27(8):e482–e490

Citera G,

Mysler E,

Madariaga H,

Cardiel MH,

Castañeda O,

Fischer A,

Richette P,

Chartrand S,

Park JK,

Strengholt S,

Rivas JL,

Thorat AV,

Girard T,

Kwok K,

Wang L,

Ponce de Leon D

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....

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Lung / ILD

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

Ann Rheum Dis. 2021 Apr 27;80(8):1004–13.

Deodhar A,

Sliwinska-Stanczyk P,

Xu H,

Baraliakos X,

Gensler LS,

Fleishaker D,

Wang L,

Wu J,

Menon S,

Wang C,

Dina O,

Fallon L,

Kanik KS,

van der Heijde D.

A Phase 3 study assesses the efficacy and safety of tofacitinib in adults with active AS.Deodhar, et al. found that ASAS20 and ASAS40 response rate significantly increased with tofacitinib 5 mg BID versus placebo at Week 16, with improvements maintained to Week 48.There were no new safety signals detected over the course of the study....

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

Highlights of 2021

Please click the links below to go to the CSF review of each paper

McInnes IB

I’m sure we’d all hoped that this year would be a return to normal but, in the midst of the challenges we’ve faced with COVID-19, the rheumatology community has continued to deliver excellent publications, and we’ve covered many of these on the CSF. Here are my highlights from 2021's publications: Points to Consider for the Treatment of Immune-Mediated Inflammatory Diseases With Janus Kinase Inhibitors: A Co...

Keywords:

• Review