October 2015

Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching

Annals of the Rheumatic Diseases. 2015 Aug 5. doi:pii: annrheumdis-2015-207784. 10.1136/annrheumdis-2015-207784. [Epub ahead of print]

This study compared the clinical outcomes at one year after the treatment either abatacept or tocilizumab in routine clinical practice. This study employed propensity score matching and demonstrated that abatacept and tocilizumab had comparable continuing efficacies, and that treatment with the drugs resulted in comparable clinical and functional remission rates. Additionally, abatacept and tocilizumab showed similar effectiveness with or without MTX.While clinical efficacies, including SDAI, w...

Calprotectin more accurately discriminates the disease status of rheumatoid arthritis patients receiving tocilizumab than acute phase reactants

Rheumatology. 2015 Aug 4. doi:pii: kev251. [Epub ahead of print]

Calprotectin is a member of the S100 protein family that has strong pro-inflammatory effects that reflect local ongoing inflammation rather than systemic response, due to its release at local inflammation sites. High calprotectin levels have been found in SF and serum from RA patients and correlate with disease activity. This study analysed the accuracy of calprotectin compared to acute phase response in discriminating the clinical disease status of RA patients receiving TCZ. A clinical assessme...

September 2015

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

Modern Rheumatology. 2015 Jul;25(4):514-21. doi: 10.3109/14397595.2014.995875.

The oral Janus kinase (JAK) inhibitor, Tofacitinib, preferentially inhibits signalling by heterodimeric receptors associated with JAK3 and/or JAK1, blocking signalling for several cytokines. The purpose of this study was to evaluate the efficacy of tofacitinib monotherapy versus placebo in Japanese patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARDs). Data on response rates – ACR20/50/70, DAS28-4(ESR), and HAQ-DI – laboratory parameters and adverse events were col...

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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]

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...

July 2015

Long-term Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan

The Journal of Rheumatology. 1 June 2015 DOI: 10.3899/jrheum.141210 [Epub ahead of print]

The humanised anti-interleukin 6 receptor monoclonal antibody tocilizumab (TCZ) has been available in clinical practice for several years. The purpose of this study was to evaluate the long-term safety of for the treatment of RA in a real-world clinical setting as a long-term extension of a single-arm, observational post marketing surveillance study. Data on selected adverse events (AEs) - fatal events, serious infection, malignancy, GI perforation, and serious cardiac dysfunction - were collect...

June 2015

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]

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...

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May 2015

Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial

Arthritis Res Ther. 2015 Apr 6;17(1):95.

Mean increases from baseline in patient serum creatinine (SCr) levels have been observed in the clinical development programme for the JAK inhibitor tofacitinib. These increases predominantly occurred within the first three months, and reversed with tofacitinib withdrawal.

This phase 1, randomised, placebo-controlled, parallel-group, 2-period study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib, relative to placebo, in 148 patients with active RA. Result...

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Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-205847. doi: 10.1136/annrheumdis-2014-205847. [Epub ahead of print]

The developments of certain malignancies associated with chronic inflammatory diseases such as RA is known to occur to a greater extent than that of the general population. It is also know that certain RA treatments can affect malignancy rates. As such, newer immunomodulatory agents, such as the JAK inhibitor tofacitinib, are closely monitored for safety events of special interest, including malignancies.

This paper analyses pooled malignancy data from the tofacitinib RA clinical develop...

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April 2015

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

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...

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The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis

Ann Rheum Dis. 2015 Mar 20. pii: annrheumdis-2014-207191. doi: 10.1136/annrheumdis-2014-207191. [Epub ahead of print]

The increased risk of serious infection among RA patients means vaccinations against pneumococcus and influenza are recommended in this group of patients. Studies evaluating immune response to these vaccines in conjunction with DMARD therapy can provide clinicians with important information relating to things such as timing of vaccination.

This study aimed to assess the effect of tofacitinib on vaccine responses to PPSV-23 and the trivalent seasonal influenza vaccine in those whom tofacit...

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