Publications

Biologic or Tofacitinib Monotherapy for Rheumatoid Arthritis in People with Traditional Disease-modifying Anti-rheumatic Drug (DMARD) Failure: a Cochrane Systematic Review and Network meta-analysis (NMA)

Cochrane Database Syst Rev 2016;11:CD012437.

Singh JA,

Hossain A,

Tanjong Ghogomu E,

Mudano AS,

Tugwell P,

Wells GA

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 (TNFis: adalimumab,...

Keywords:

• JAK,
• Tofacitinib,
• Meta analysis

Biologics or Tofacitinib for Rheumatoid Arthritis in Incomplete Responders to Methotrexate or Other Traditional Disease-Modifying Anti-Rheumatic Drugs: A Systematic Review and Network Meta-Analysis

Cochrane Database of Systematic Reviews 2016 Issue 5. Art. No.: CD012183 [DOI: 10.1002/14651858.CD012183].

Singh et al

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 head-to-head studies to show any important differences between these options in terms of benefits and harms. This review provides an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for RA.1Nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, a...

Keywords:

• JAK,
• Tofacitinib,
• Meta analysis

Risk for Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologics

Arthritis Rheumatol. 2016 May 17. DOI 10.1002/art.39761 [Epub ahead of print]

Xie et al.

Historically, patients with RA have suffered with upper tract gastrointestinal perforation (GIPs), associated with NSAID use. More recently, the IL-6 receptor antagonist tocilizumab (TCZ) has been associated with lower tract GIPs. Janus kinase (JAK) inhibitors, including tofacitinib (TOF), with some downstream effects on IL-6 signalling, also have potential for an increased risk of GIPs.There is limited real-world evidence and almost no comparative evidence on the risk for GIP associated with TC...

Keywords:

• IL-6,
• Tocilizumab,
• Safety,
• GI

Real-world Comparative Risks of Herpes Virus Infections in Tofacitinib and Biologic-treated Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2016 Apr 25;0:1–5 doi: 10.1136/annrheumdis-2016-209131

Curtis et al.

Herpes Zoster (HZ) complications can cause considerable morbidity including debilitating pain syndromes. Clinical trials of tofacitinib have suggested it may increase the risk of HZ. Although unclear, the mechanism may involve reduced CD4 T-cell function and interference of interferon signalling. Following approval of tofacitinib in the US in 2012, real-world data from Medicare (2006–2013) and from the US longitudinal database, Marketscan, (2010–2014) were analysed. A total of 2526 patients who...

Keywords:

• JAK,
• Tofacitinib,
• Real-World,
• Infections

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients

Adv Ther. 2016 Mar 12. DOI 10.1007/s12325-016-0312-y

Chastek et al.

Biologics are used to treat several inflammatory diseases, including RA, PsO, PsA, and AS; however, the cost of biologic therapies is high compared to non-biologic DMARDs. By using evidence-based assessment of comparative costs between biologics, healthcare resources can be properly allocated. This study used medical and pharmacy claims data to assess the utilitisation and cost of biologic treatment for RA, PsO, PsA, and AS. ETN (45%), ADA (32%), and INF (9%) were the most common medications and...

Keywords:

• JAK,
• Cost / Cost Effectiveness,
• Review

Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis

Ann Rheum Dis 2016;0:1–6 doi:10.1136/ annrheumdis-2015-207870 [Epub ahead of print]

Zhang et al.

Since RA patients are at an increased risk of a CV event, there have been several studies to determine if RA treatments alter this risk. In a retrospective study, Zhang and colleagues assess the risk of CV events in patients initiating bDMARDs.Using Medicare medical and pharmacy claims data, the incidence rate (IR) of acute myocardial infarction (AMI) and of a composite CHD* was calculated across RA patients initiating 8 different biologics: ABA, ADA, CER, ETA, GOL, INF, RIT, and TOC. There were...

Keywords:

• Safety,
• Cardiovascular

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials

Arthritis Res Ther. 2015 Dec 15;17(1):362

Strand V,

Ahadieh S,

French J,

Geier J,

Krishnaswami S,

Menon S,

Checchio T,

Tensfeldt TG,

Hoffman E,

Riese R,

Boy M,

Gomez-Reino JJ

Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. By modulating the signalling of cytokines that are integral to lymphocyte activation, proliferation, and function, tofacitinib may suppress multiple elements of immune response. A systematic literature search including all biologics and tofacitinib procured 66 RCTs and 22 LTEs that were included in a meta-analysis to provide estimated incidence rates, risk ratios, and risk differences of serious infection for each therapy. Es...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Meta analysis,
• Infections

Lipid profile changes in patients with chronic inflammatory arthritis treated with biologics and tofacitinib in randomized clinical trials: A systematic review and meta-analysis

Arthritis Rheumatol. 2015;67(1):117–127

Souto A,

Salgado E,

Maneiro JR,

Mera A,

Carmona L,

Gómez-Reino JJ

Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials.

The s...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Cardiovascular

What is the future of targeted therapy in rheumatology: biologics or small molecules?

BMC Medicine 2014, 12:43

Moscai A,

Kovace L and Gergely P

Our understanding of inflammatory rheumatic diseases such as rheumatoid arthritis has significantly increased over the last 20 years. With this greater understanding we have seen a significant improvement in the therapy of RA and other inflammatory rheumatic diseases. In this review, Moscai et al. discuss the improvements in therapies for the treatment of these diseases from the introduction of methotrexate as a frontline therapy through to the current era and approval of the first small molecul...

Keywords:

• Review

Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets

Rheumatology doi:10.1093/rheumatology/ket414

Furst DE and Emery P

Despite biologic therapies greatly improving the treatment of rheumatoid arthritis, many patients do not respond to current treatments or do not maintain response to these treatments. This review covers the evidence for the newly discovered role of Th17 cells, IL-12 and IL-17 family of cytokines in the pathogenesis of RA as well as the development of new therapies targeting these cytokines. With current biologics targeting cytokines such as TNF, IL-1ß and IL-6, the discovery of the Th17 subset o...

Keywords:

• MOA,
• Review