Publications

Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis

Ann Rheum Dis. 2015;0:1-7. doi:10.1136/annrheumdis-2015-207872 [Epub ahead of print]

Gabay C,

McInnes IB,

Kavanaugh A,

Tuckwell K,

Klearman M,

Pulley J,

Sattar N

RA patients have increased risk of CVD compared with the general population that is not fully explained by traditional risk factors. This is a post-hoc analysis of data from a clinical trial that compared IL-6 and TNF-α signaling inhibition to compare changes in lipids and lipid-associated CV risk markers in 324 patients treated with TCZ IV q4w or ADA SC q2w for 24 weeks. HDL-SAA and sPLA2 IIA is also measured in an additional subpopulation of 87 and 97 TCZ and ADA patients, respectively.Greater...

Keywords:

• IL-6,
• Tocilizumab,
• Safety,
• Cardiovascular

Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study

Arthritis Research & Therapy (2015) 17:319 DOI: 10.1186/s13075-015-0835-7

Curtis JR,

Sarsour K,

Napalkov P,

Costa LA,

and Schulman KL

Interstitial lung disease (ILD) is a common extra-articular condition for RA patients. This retrospective cohort study of health insurance databases investigates the ILD incidence and exacerbation between ABA, TCZ, RTX, and anti-TNFα agents in adult RA patients with prior biologic therapy. Two definitions of ILD were used: one specific, one sensitive; descriptive results were produced for both. In patients with no history of ILD, the overall incidence rate of ILD ranged from 1.8% to 6.4% (depend...

Keywords:

• IL-6,
• Tocilizumab,
• Safety,
• Lung / ILD

Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibition

Annals of the Rheumatic Diseases. 2015 Sep 9. doi:10.1136/annrheumdis-2014-207201

W Gao,

T McGarry,

C Orr,

J McCormick,

D J Veale,

U Fearon

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis (Ps) and characterised by synovitis and progressive destruction of articular cartilage and bone. Recently developed agents for PsA target IL12p40, IL-6 and IL-17, several of which signal through the JAK family of receptor-associated tyrosine kinases. Tofacitinib is a drug of the JAK inhibitor class and is currently approved for the treatment of RA in 27 countries. This study evaluated the effect of tofacitini...

Keywords:

• JAK,
• Tofacitinib,
• Basic Science,
• Review

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study

Ann Rheum Dis. 2015 Sep 15. doi:10.1136/ annrheumdis-2015-207760

C Gabay,

M Riek,

ML Hetland,

EM Hauge,

K Pavelka,

M Tomšič,

H Canhao,

K Chatzdionysiou,

G Lukina,

DC Nordström,

E Lie,

I Ancuta,

MV Hernández,

PLMC van Riel,

R van Vollenhoven,

TK Kvien

Biological DMARDs have markedly changed the management and outcome of rheumatoid arthritis. Most international guidelines recommend the use of biological DMARDs in combination with MTX or other synthetic DMARDs (sDMARDs) (where MTX is not tolerated or contraindicated), based primarily on the observation that MTX enhances the efficacy of TNF antagonists in both clinical trials and observational studies.This study examined the effectiveness of tocilizumab (TCZ), an anti-IL-6 monoclonal antibody, ...

The Efficacy and Safety of Subcutaneous Clazakizumab in Patients with Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results from a Phase IIb, Randomized, Double-Blind, Placebo/Active-Controlled, Dose-Ranging, Multinational Study

Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

Weinblatt ME,

Mease P,

Mysler E,

Takeuchi T,

Drescher E,

Berman A,

Xing J,

Zilberstein M,

Banerjee S,

Emery P

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collected from 418 patie...

TNF-α and IL-6 differentially regulate Dkk-1 in the inflamed arthritic joint

Arthritis Rheumatol. 2015 May 4. doi: 10.1002/art.39183. [Epub ahead of print]

Yeremenko N,

Zwerina K,

Rigter G,

Pots D,

Fonseca J,

Zwerina J,

Schett G,

Baeten D.

Different inflammatory joint diseases have distinct patterns of bone damage, but the molecular pathways determining each one remains poorly defined. This study investigates the wingless (Wnt)-signalling pathway, by analysing the expression of Dkk-1 (an inhibitor of the Wnt pathway) and its regulation by the pro-inflammatory cytokines TNF-α and IL-6 in SpA versus RA inflamed peripheral joints.Findings from the study show an inverse correlation of Dkk-1 with IL-6 in vivo and a differential regulat...

Keywords:

• IL-6,
• Basic Science,
• MOA,
• Review

The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis

Arthritis Res Ther. 2015 May 20;17(1):135. [Epub ahead of print]

Van Roy M,

Ververken C,

Beirnaert E Hoefman S,

Kolkman J Vierboom M,

Breedveld E,

't Hart B,

Poelmans S,

Bontinck L,

Hemeryck A,

Jacobs S,

Baumeister J,

Ulrichts H

Over the last decade, there has been a shift in treatment outcomes for RA; moving from symptom control to achieving remission. The TNF inhibitors have revolutionised treatment in this way, yet there is still a proportion of patients who fail to improve or reach remission. As such, new molecules for the treatment of RA are needed to be developed.This study investigates the in vitro and in vivo properties of ALX-0061, a bispecific Nanobody with a high affinity and potency for IL-6R.Positive pharma...

Keywords:

• IL-6,
• Preclinical,
• MOA,
• Review

Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a phase III study

Arthritis Rheumatol. Vol. 67, No. 6, June 2015, pp 1424–1437

Genovese MC,

Fleischmann R,

Kivitz A et al.

Biologic DMARDs targeting TNF-alpha, IL-1, T-cell co-stimulatory blockade, B-cell depletion, and IL-6R, as well as the newer JAK inhibitors have greatly improved clinical outcomes in RA. However, not all patients respond to current biologic or small molecule DMARDs.

Sarilumab is a fully human anti-IL-6Rα mAb that binds membrane-bound and soluble human IL-6R with high affinity, blocking cis and trans IL-6-mediated signalling. This study (MOBILITY) is the first randomised, double-blin...

Keywords:

• IL-6,
• Phase 3

IL-6 stimulates intestinal epithelial proliferation and repair after injury

PLoS One. 2014 Dec 5;9(12):e114195. doi: 10.1371/journal.pone.0114195. eCollection 2014.

Kuhn KA,

Manieri NA,

Liu TC,

Stappenbeck TS.

IL-6 is an inflammatory cytokine known to contribute to a number of autoimmune diseases such as RA. Therapies targeting the soluble IL-6 receptor have now become effective treatments for RA. However, one unforeseen, yet rare, potential complication of anti-IL-6 therapy is bowel perforation. Yet within the intestine, IL-6 protects intestinal epithelial cells from apoptosis during prolonged inflammation.

The authors hypothesized that IL-6 may have beneficial properties in wound response/rep...

Keywords:

• IL-6,
• Preclinical