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

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

Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3

RMD Open. 2021;7(2):e001621.

Aletaha D,

Westhovens R,

Gaujoux-Viala C,

Adami G,

Matsumoto A,

Bird P,

Messina OD,

Buch MH,

Bartok B,

Yin Z,

Guo Y,

Hendrikx T,

Burmester GR.

Post hoc analysis of the phase III FINCH study shows that filgotinib may be an alternative treatment option for patients with RA who have poor prognostic factors (PPFs), especially those not responding to standard treatment such as methotrexate (MTX).PPFs are associated with severe disease and risk for disease progression in patients with RA. Consequently, the 2019 EULAR management guidelines for RA recommend early treatment escalation for patients with PPFs who have inadequate response to first...

Keywords:

• JAK,
• Fenebrutinib,
• Efficacy,
• Safety,
• Phase 3

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

Traves PG,

Murray B,

Campigotto F,

Galien R,

Meng A,

Di Paolo JA

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type.Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, ST...

Keywords:

• JAK,
• Basic Science,
• MOA

Filgotinib, a Novel JAK1-Preferential Inhibitor for the Treatment of Rheumatoid Arthritis: An Overview from Clinical Trials

Mod Rheumatol. 2021 Mar 19:1-26. Epub ahead of print. DOI 10.1080/14397595.2021.1902617

Tanaka Y,

Kavanaugh A,

Wicklund J,

McInnes IB

Filgotinib is the latest JAKinib to enter the international market for the treatment of RA, receiving regulatory approval in Japan and Europe late last year. In this review paper, Tanaka Y et al. examine the clinical evidence supporting its use as a later-line treatment, in accordance with international RA management guidelines, and provide their expert opinions on JAKinibs from a clinical perspective.The core clinical programme evaluating filgotinib in patients with moderately-to-severely activ...

Keywords:

• JAK,
• Fenebrutinib,
• Review

Safety and Efficacy of Filgotinib: Up to 4-Year Results From an Open-Label Extension Study of Phase 2 Rheumatoid Arthritis Programs

J Rheumatol. 2021 Feb 1:jrheum.201183. DOI: 10.3899/jrheum.201183.

Kavanaugh A,

Westhovens RR,

Winthrop KL,

Lee SJ,

Tan Y,

An D,

Ye L,

Sundy JS,

Besuyen R,

Meuleners L,

Stanislavchuk M,

Spindler AJ,

Greenwald M,

Alten R,

Genovese MC

A long-term extension study of filgotinib showed consistent safety profile and sustained efficacy with the drug for up to four years. The DARWIN 3 study, for patients who previously completed either the 24-week DARWIN 1 study (filgotinib + MTX) or the DARWIN 2 study (filgotinib monotherapy), enrolled 739 patients with RA. At the time of analysis, 440 patients had received four years or more of filgotinib. Exposure-adjusted incidence rate per 100 patient-years-of-exposure for TEAEs was 24.6 in th...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 2,
• LTE

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial

Ann Rheum Dis. 2021 Jan 15:annrheumdis-2020-219213.

Westhovens R,

Rigby WF,

van der Heijde D,

Ching DW,

Stohl W,

Kay J,

Chopra A,

Bartok B,

Matzkies F,

Yin Z,

Guo Y,

Tasset C,

Sundy JS,

Jahreis A,

Mozaffarian N,

Messina OD,

Landewé R BM,

Atsumi T,

Burmester GR

Filgotinib doses in combination with MTX have shown improved signs, symptoms and physical function in patients with RA and limited or no prior MTX exposure. FIL 200mg monotherapy did not have a superior ACR20 response rate versus MTX. This 52-week, phase 3 study evaluated FIL in 1252 patients with RA. Patients were randomised to FIL 200mg + MTX or FIL 100mg + MTX, FIL 200 mg monotherapy, or MTX monotherapy. The primary endpoint was the proportion patients achieving ACR20 at week 24. Safety was e...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 3

Filgotinib Versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Phase III Randomised Clinical Trial

Ann Rheum Dis. 2021 Jan 27:annrheumdis-2020-219214

Combe B,

Kivitz A,

Tanaka Y,

van der Heijde D,

Simon JA,

Baraf HSB,

Kumar U,

Matzkies F,

Bartok B,

Ye L,

Guo Y,

Tasset C,

Sundy JS,

Jahreis A,

Genovese MC,

Mozaffarian M,

Landewé RBM,

Bae S-C,

Keystone EC,

Nash P

Filgotinib improved RA signs and symptoms, physical function, and inhibited radiographic progression. FIL 200mg plus MTX, but not FIL 100mg plus MTX showed non-inferiority to ADA plus MTX, based on DAS28(CRP) low disease activity. FIL was also well tolerated in RA patients with inadequate response to MTX.This 52-week, phase 3 randomised clinical trial (FINCH 1) evaluated the efficacy and safety of FIL in patients with RA randomised to FIL 200 or 100mg, ADA 40mg, or placebo, all with background M...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 3

Highlights of 2020

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

McInnes. I

2020 unfolded apace, dominated by COVID-19 - we have all had to adapt in our practice and in our knowledge base. Amid this there have continued to be a constant flow of publications and science in cytokine signaling, and as in previous years as we come the end of 2020, I will highlight some of the notable papers of the year. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respective detailed summaries below:

Keywords:

• Review