Publications

Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

Auto Immun Highlights. 2021;12(1):8.

Solipuram V,

Mohan A,

Patel R,

Ni R.

The combination of JAK inhibitors with MTX is not associated with an increased risk of malignancy when compared to MTX alone. Although long-term studies are needed to confirm this conclusion from short-term studies. Although it is now known that patients with RA are predisposed to an increased risk of malignancy, especially malignant lymphomas, lung cancers and non-melanoma skin cancer, it remains unclear whether the combination therapy is associated with a higher risk.To this end, Solipuram, et...

Keywords:

• JAK,
• Meta analysis,
• Safety,
• Malignancy

Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study

Rheumatol Ther. 2021;8(2):903–919

Mease PJ,

Lertratanakul A,

Papp KA,

van den Bosch FE,

Tsuji S,

Dokoupilova E,

Keiserman MW,

Bu X,

Chen L,

McCaskill RM,

Zueger P,

McDearmon-Blondell EL,

Pangan AL,

Tillett W.

Fifty-six-week data suggest that upadacitinib could be a favourable long-term treatment option in patients with PsA who are refractory to biologic therapy.As the need for additional therapeutic agents that can effectively control disease activity continues, new data from a 56-week analysis of the oral reversible JAK1 inhibitor, upadacitinib, currently under investigation for the treatment of PsA, shows that efficacy of the drug is maintained over the duration of this study.Mease, et al. explored...

Keywords:

• JAK,
• Updacitinib,
• Phase 3,
• Safety,
• Efficacy

Tofacitinib versus tocilizumab in the treatment of biological-naïve or previous biological-failure patients with methotrexate-refractory active rheumatoid arthritis

RMD Open. 2021;7(2):e001601.

Mori S,

Urata Y,

Yoshitama T,

Ueki Y.

Findings from a multicentre cohort study in Japan provide important information that is expected to aid in determining the position of tofacitinib in the treatment algorithm for RA.Mori S, et al. compared therapeutic outcomes, from real-world registries, at 12 months between tofacitinib-treated and tocilizumab-treated patients to clarify whether tofacitinib should only be considered as an option for patients who have either failed to respond to at least one bDMARD or are MTX-resistant/-intoleran...

Keywords:

• JAK,
• IL-6,
• Tofacitinib,
• Tocilizumab,
• Efficacy,
• Safety

Comparative efficacy and safety of secukinumab, ixekizumab, and tofacitinib in patients with active psoriatic arthritis showing insufficient response to tumor necrosis factor inhibitors

Int J Clin Pharmacol Ther. 2021. Epub ahead of print.

Song GG,

Lee YH.

Bayesian network meta-analysis of randomised controlled trials (RCTs) highlights the effectiveness of secukinumab, ixekizumab, and tofacitinib in patients with psoriatic arthritis (PsA) and an inadequate response to tumour necrosis factor inhibitors (TNFi).There is a current need for therapies with alternative mechanisms of actions to DMARDs and TNFi, for the significant proportion of patients with PsA who insufficiently respond to these therapies. While RCTs for therapies such as secukinumab a...

Keywords:

• JAK,
• IL-17,
• Secukinumab,
• Tofacitinib,
• Efficacy,
• Safety

Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis

N Engl J Med. 2021;384(13):1227-1239.

McInnes IB,

Anderson JK,

Magrey M,

Merola JF,

Liu Y,

Kishimoto M,

Jeka S,

Pacheco- Tena C,

Wang X,

Chen L,

Zueger P,

Liu J,

Pangan AL,

Behrens F.

Upadacitinib efficacy proves to be greater than placebo, and non-inferior to adalimumab, in treating patients with psoriatic arthritis (PsA). Already approved for the treatment of rheumatoid arthritis, McInnes, et al. studied oral upadacitinib at a dose of 15 mg or 30 mg, alongside placebo or adalimumab, in this 24-week, Phase III trial, in over 1700 patients with PsA. At the primary endpoint (Week 12), ACR20 response was greater with upadacitinib than placebo, and non-inferior to adalimumab; wi...

Keywords:

• JAK,
• Updacitinib,
• Review

Risk of venous thromboembolism associated with tofacitinib in patients with rheumatoid arthritis: a population-based cohort study

Rheumatology (Oxford). 2021 Mar 22:keab294. Epub ahead of print. DOI: 10.1093/rheumatology/keab294

Desai RJ,

Pawar A,

Khosrow-Khavar F,

Weinblatt ME,

Kim SC

A population-based cohort study of 87,653 RA patients has found no evidence for an increased risk of venous thromboembolism (VTE) for tofacitinib, versus TNFis, in patients with RA.The introduction of JAKinibs, almost a decade ago, has provided an important oral option for the treatment of RA. However, in recent years, a safety concern, relating to incidence of VTE after treatment, has emerged. Consequently, both the US and European regulatory authorities now recommend caution for use of tofacit...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Real-World

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

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-w

Conaghan PG,

Mysler E,

Tanaka Y,

Da Silva-Tillmann B,

Shaw T,

Liu J,

Ferguson R,

Enejosa JV,

Cohen S,

Nash P,

Rigby W,

Burmester G

Upadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme.In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integrated safety revie...

Keywords:

• JAK,
• Updacitinib,
• Phase 3,
• 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