May 2021

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.

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...

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Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies

Rheumatology (Oxford). 2021;60(4):1708-1716.

Long-term evaluation of tofacitinib has found limited progression of structural damage in patients with RA treated with tofacitinib for up to 5 years. Similar results were also observed for patients receiving tofacitinib monotherapy or combination therapy for up to 3 years.It is well known that inflammation in RA leads to structural damage over time, and therapies such as DMARDS have the ability to reduce inflammation whilst inhibiting the progression of structural damage. In this study, van der...

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April 2021

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

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...

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Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain.Based on clinic...

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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

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...

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March 2021

Effects of One-Year Tofacitinib Therapy on Bone Metabolism in Rheumatoid Arthritis

Osteoporos Int 2021 Feb 9 DOI 10.1007/s00198-021-05871-0

Thought to be the first study of its kind, Hamar, et al. have demonstrated the effect of one-year tofacitinib treatment on bone mineral density (BMD) in RA patients. While the association between RA and osteoporosis is well known, and evidence indicates that up to 70% of these patients have reduced BMD, little information is available on how the JAK inhibitor tofacitinib affects bone status, areal and volumetric BMD, and bone turnover markers. In this prospective study, 30 patients were assessed...

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February 2021

Upadacitinib Monotherapy Versus Methotrexate Monotherapy in Methotrexate-naïve Japanese Patients with Rheumatoid Arthritis: A Sub-analysis of The Phase 3 SELECT-EARLY study

Mod Rheumatol 2021;26:1–16.

In this sub-analysis of the Phase 3 SELECT-EARLY study, UPA demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Along with a favourable efficacy observed with the Japan-specific 7.5 mg dose of UPA for all secondary endpoints. SELECT-EARLY was designed to study the safety and efficacy of UPA 15 and 30mg as monotherapy, but it also included a subset of 138 Japanese patients, 40% of whom were randomised to receive UPA 7.5mg. This was designed to meet the requirements o...

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Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity

PLoS ONE 2021;16(1):e0244187

This analysis provides evidence that immune cell signalling pathways are important in RA. There were consistent differences between RA patients and healthy controls in IFNα, IL-6, IL-10 and GM-CSF+ IL-2 induced JAK/STAT signalling in multiple immune cell subsets.We know that RA is characterised by dysregulation of immune responses, but the exact cause is unknown. Recently, single-cell transcriptomics and mass cytometry confirmed the critical role of activated immune cells and fibroblasts, increa...

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Baricitinib Inhibits Structural Joint Damage Progression in Patients with Rheumatoid Arthritis – A Comprehensive Review

Arthritis Res Ther 2021;23(1):3.

MRI studies have shown that BARI reduces joint inflammation and damage in patients with moderate-to-severe active RA. This review summarises the effects of BARI on structural joint damage progression and the mechanisms underlying these effects, using MRI data from across the clinical trial program. Early preclinical animal models showed a significant reduction in joint inflammation, ankle width, and bone resorption. Efficacy and safety of BARI have been confirmed in an extensive programme, inclu...

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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

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...

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