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

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, ...

Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial

Modern Rheumatology. 2015 Sep 10:1-9. [Epub ahead of print]

Takeuchi T,

Tanaka Y,

Yamanaka H,

Amano K,

Nagamine R,

Park W,

Shiozawa K,

Tsukano M,

Wei J,

Shao J,

Togo O,

Mashimo H

This Phase II study assessed the safety and efficacy of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy. After 12 weeks of treatment, olokizumab was found to rapidly improve disease activity in patients who had previously failed anti-TNF therapy. There was also a significant decrease in ACR20 and ACR50 responder rates at week 12. The safety findings were consistent with the safety profile expected for this drug class. These findin...

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

Differential Effects of IL-17A and TNF-α on Osteoblastic Differentiation of Isolated Synoviocytes and on Bone Explants from Arthritis Patients

Frontiers in Immunology. 2015;6:151. doi:10.3389/fimmu.2015.00151

Osta B,

Roux JP,

Lavocat F,

Pierre M,

Ndongo-Thiam N,

Boivin G,

Miossec P

Inflammatory joint diseases such as RA and OA are characterised by bone and consequent joint destruction. The role of fibroblast-like synoviocytes (FLS) in the pathogenesis of such diseases is already established. This study compared the effects of TNF-α and IL-17A on osteogenic differentiation of isolated FLS and on whole bone explants from 3 RA and 10 OA patients.Results showed that isolated RA-FLS appeared more sensitive to the effects of TNF-α and IL-17A compared to OA-FLS. These findings su...

Keywords:

• IL-17,
• Basic Science

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