Publications

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

Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Phase 3 Trials of Baricitinib

ACR Open Rheumatol. 2021. Epub ahead of print. doi: 10.1002/acr2.11380

Pope JE,

Lee YC,

Curtis JR,

Mo D,

Xie L,

Dickson CL,

Schlichting DE,

Cardoso A,

Simon LS,

Taylor PC

This post hoc analysis shows that pain reduction was similar between opioid users and nonusers with baricitinib 2 mg and 4 mg, but not adalimumab.Use of opioids to treat RA-related pain has increased, yet long-term use has been associated with reduced efficacy and safety concerns. In addition, the misuse of opioids has resulted in a public health crisis in the United States and highlights the need for safe, effective nonaddictive alternatives for pain management. As such, Pope, et al. assessed p...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Pain

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

Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years

Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-221051

Winthrop KL,

Tanaka Y,

Takeuchi T,

Kivitz A,

Matzkies F,

Genovese MC,

Jiang D,

Chen K,

Bartok B,

Jahreis A,

Besuyen R,

Burmester GR,

Gottenberg JE

Integrated analysis evaluates the safety of filgotinib among patients with RA treated for a median of 1.6 years.Winthrop, et al. analysed data from seven trials, including long-term extension studies, and found that rates of TEAEs, grade ≥3 TEAEs, serious TEAEs and TEAEs leading to study drug discontinuation were comparable for filgotinib and placebo. In addition, analysis of AEs of special interest showed a generally similar incidence for filgotinib 200 mg and 100 mg....

Keywords:

• JAK,
• Fenebrutinib,
• Safety,
• Review

Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial

Lancet. 2021;398(10315):1984–96

Ruperto N,

Brunner HI,

Synoverska O,

Ting TV,

Mendoza CA,

Spindler A,

et al.

Pivotal trial data show that tofacitinib is an effective treatment in patients with polyarticular course juvenile idiopathic arthritis (pJIA).New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. To this end, Ruperto, et al. assessed the efficacy and safety of tofacitinib versus placebo in patients with pJIA (N=225). They observed a JIA flare rate at Week 44 of 29% and 53% for tofacitinib and placebo, respectively. Safety results were si...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3