Cytokine Signalling Forum


December 18

Professor Iain McInnes Reviews the Most Notable Papers from 2018

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

2018 brought a wealth of new data in cytokine signalling and IL-6 that helps inform current clinical practice and brings the promise of new options in the future. There was good data on the use of sub cutaneous tocilizumab as well as strategies in early RA and for methotrexate tapering. For the currently marketed JAK inhibitors, tofacitinib and baricitinib, continuous long-term efficacy and safety data further support its current use and applications. On the development side, the outcomes of the...

February 18

Professor Iain McInnes Reviews the Most Important Papers from 2017

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

2017 was a successful year for rheumatoid arthritis research, with some key advances in JAK inhibitors and IL-6 inhibitors, as outlined below. - Tofacitinib was suggested as a potential treatment for psoriatic arthritis, and NICE recommended tofacitinib as a treatment for moderate to severe rheumatoid arthritis - Baricitinib studies supported the potential use of baricitinib as a treatment for rheumatoid arthritis - Filgotinib Phase 2 studies suggested that filgotinib could be effect...

December 16

TNF Inhibitörlerine Yetersiz Yanıtlı Aktif Romatoid Artrit Hastalarında Tofasitinib ve Biyolojik Tedavilerin Karşılaştırılması: Bir Network Meta Analizinin Sonuçları

Vieira M-C, Zwillich SH, Jansen JP, Smiechowski B, Spurden D and Wallenstein GV.
Clin Ther 2016;38:2628–40.

This network meta-analysis, performed within a Bayesian framework, concluded that tofacitinib 5 mg BID has efficacy and AE rates comparable with currently available bDMARDs over a 24-week period in patients experiencing an inadequate response to TNF therapy. A systematic literature search identified five, Phase 2 or beyond, randomised controlled trials for inclusion in the analysis. Each trial had an adult population with moderate to severe RA, with inadequate response (IR) or failed treatment...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Bahtiyar Toz

Geleneksel Hastalık Modifiye Edici Anti-romatizmal İlaç (DMARD) Başarısız Romatoid Artrit Hastalarında Biyolojik veya Tofasitinib Monoterapi: Cochrane Sistematik Derlemesi ve Network Meta-analizi

Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, Tugwell P, Wells GA.
Cochrane Database Syst Rev 2016;11:CD012437.

Treatment options for RA patients who are MTX/DMARD incomplete responders (IR) include other DMARDs, biologics or tofacitinib (TOF). However, there is a lack of direct head-to-head comparator trials of biologics in people with RA. This review provides an update of the 2009 Cochrane overview, ‘Biologics for rheumatoid arthritis’,1 and provides comparisons and estimates for biologic or TOF monotherapy in MTX/DMARD-IR people with RA. The benefits and harms of biologic monotherapy (TNFi...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Bahtiyar Toz

February 14

Konvansiyonel DMARD, Glukokortikoidler ve Tofasitiniblerin etkinliği: RA tedavisinde EULAR 2013 önerileri hakkında bilgilendiren sistematik literatür derlemesi

Gaujoux-Viala C, Nam J, Ramiro S.
Ann Rheum Dis doi:10.1136/annrheumdis-2013-204588

Systematic literature reviews were undertaken to assess the efficacy of csDMARDs, glucocorticoids and tofacitinib in the treatment of RA. The first two were updates to reviews conducted for the 2010 recommendations while the tofacitinib SLR was a complete review. Two studies identified by the csDMARD SLR, tREACH and TEAR, compared efficacy between MTX mono- and combination therapy (MTX+SSZ+HQ). Both of these studies found there was no benefit to immediate triple therapy. Further studies analysin...

Keywords: Cytokine Signalling, Clinical, Efficacy

Translated by: Bahtiyar Toz

October 13

Involvement of JAK/STAT signalling in the pathogenesis of inflammatory bowel disease

Coskun M, Salem M, Pedersen J, Nielsen OF.
Pharmacological Research 2013; 76:1–8

The JAK/STAT signalling pathway has been implicated in the pathogenesis of several inflammatory diseases including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). In this review, Coskun et al. provide an excellent background overview of the JAK/STAT cascade. They also highlight recent study findings investigating the mechanisms of the JAK/STAT pathway and the anti-inflammatory effects of novel JAK inhibitors in development and in clinical trials, particularly in IBD. In one study...

A meta-analysis of p38 mitogen-activated protein kinase inhibitors in patients with active rheumatoid arthritis

Li L, Li G, Yu C, Li Y.
Clinical Rheumatology 2013 doi 10.1007/s10067-013-2340-1

The role of p38-MAPK inhibitors in treating RA is the subject of some debate. Li et al. therefore performed the first meta-analysis of the current data to evaluate the efficacy and safety of these compounds. The authors identified 3 papers, covering 4 RCTs, for analysis and the results showed that p38-MAPK inhibition achieves a better level of ACR20 improvement vs. placebo, but showed no meaningful difference in ACR50, DAS28 or CRP levels past week 12. Due to the inadequate number and quality of...

August 13

Targeting the SYK-BTK axis for the treatment of immunological and hematological disorders: recent progress and therapeutic perspectives

Tan SL, Liao C, Lucas MC, et al.
Pharmacol Ther. 2013 May; 138(2):294–309

This review focuses on targeting spleen tyrosine kinase (SYK) and Bruton’s tyrosine kinase (BTK) inhibitors as potential immunomodulatory agents for the treatment of autoimmune and inflammatory disorders with SYK inhibition showing encouraging efficacy in patients with RA. The paper describes the role of SYK and BTK in several therapy areas including autoimmune diseases, allergic inflammatory disorders and haematological cancers as well as their role in innate immunity and regulators of ad...

June 13

Intracellular Signal Pathways: Potential for Therapies

Mavers M, Ruderman EM, Perlman H.
Current Rheumatology Reports 2009; 11:378-85

With recent progress in the development of drugs targeting signalling pathways for rheumatoid arthritis, this review article from the National Institutes of Health (NIH) provides an overview of the key intracellular pathways involved in the pathogenesis of rheumatoid arthritis. This paper also discusses some of the limitations of current drug targets including lack of clinical efficacy, potential adverse effects and cost, and highlights important issues associated with the design of target drugs...

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes

Riese RH, Krishnaswami S, Kremer J.
Best Practice & Research Clinical Rheumatology 2010; 24:513-26

This article reviews data from animal and phase 2 clinical studies assessing the immunomodulatory effects and pharmacokinetics of CP-690,550 (now known as tofacitinib), as well as its efficacy and safety in patients with rheumatoid arthritis (RA). In two rodent models of arthritis, CP-690,550 produced dose-dependent decreases in signs of disease activity compared with untreated controls, reductions in histologically assessed inflammation and articular cartilage damage, and statistically signific...

Back to the future: oral targeted therapy for RA and other autoimmune diseases

O'Shea JJ, Laurence A, McInnes IB.
Nature Reviews Rheumatology 2013; 9(3):173-82

This review paper considers how advances in understanding of the disease process underlying rheumatoid arthritis (RA) and the development of novel techniques have transformed the management of this progressively disabling condition. Physicians are no longer limited to prescribing symptomatic treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) or choosing from a seemingly random array of drugs drawn from multiple disciplines, such as methotrexate and sulphasalazine, which are descri...