MICA and NKG2D variants as risk factors in spondyloarthritis: a case-control study.

The major histocompatibility complex class I polypeptide-related sequence A (MICA) glycoprotein mediates the activation of the natural killer group 2D receptor (NKG2D) expressed on NK and CD8+ T cells. A methionine or valine at position 129 in exon 3 results in strong (MICA129 met) or weak (MICA129 val) binding to NKG2D. The MICA A5.1 allele causes a premature stop codon. Various NKG2D polymorphisms are associated with low (NKC3 C/C and NKC4 C/C) or high (NKC3 G/G and NKC4 T/T) levels of NK cell cytotoxic activity. In 162 patients with spondyloarthritis (115 with ankylosing spondyloarthritis, 46 with psoriatic arthritis and 1 with reactive arthritis) compared to 124 healthy controls, MICA-129 with methionine allele was more frequent in patients with spondyloarthritis (odds ratio (OR) (95% confidence interval) = 4.84 (2.75‒8.67)), whereas MICA-129 val/val, MICA A5.1 and NKC3 C/C variants were less frequent (OR = 0.20 (0.11‒0.37), 0.15 (0.06‒0.36) and 0.24 (0.13‒0.44), respectively). After adjustment for HLA-B*27 status, only NKC3 C/C remained linked to spondyloarthritis (adjusted OR = 0.14 (0.06‒0.33)). Homozygosity for MICA A5.1 is linked to ankylosing spondyloarthritis, and NKC3 C/C and MICA-129 val/val to psoriatic arthritis. MICA and NKC3 polymorphisms (related to a low NK cell cytotoxic activity) constituted a genetic association with spondyloarthritis.

Decrease of Tocilizumab Dose in Patients with Rheumatoid Arthritis: A Pilot Study.

BACKGROUND: The efficacy and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) are well demonstrated. Doses of 4 and 8 mg/kg are used intravenously. The objective of our study was to report the efficacy and safety for a set of patients who had an 8 mg/kg doze of TCZ and for another set who had this treatment first at a dose of 8 followed by 4 mg/kg. METHODS: All RA patients treated with TCZ in a University Hospital Centre Department of Rheumatology between January 2010 and December 2014 were included. Sixty-three patients received TCZ at a dose of 8 mg/kg and 19 patients received this treatment first receiving a dose of 8 mg/kg decreased to 4 mg/kg. The demographic characteristics, the clinical response and adverse events were reported. RESULTS: At the end of follow-up, 48% of patients were in clinical remission defined by disease activity score based on 28 joints with an erythrocyte sedimentation rate <2.6 in the 8 mg/kg group and 74% of patients in the 8-4 mg/kg. The rates of severe infections were 4.8 per 100 patients-years (PY) in the 8 mg/kg group and 2.9 per 100 PY in the 8 then 4 mg/kg. The infections were mainly pulmonary, ENT and skin infections. CONCLUSION: Our study reported the efficacy and safety of the TCZ in patients with RA in 'real life' with the dose of 8 mg/kg or 8 then 4 mg/kg.

Baseline MRI inflammation is not a determinant of 5-year bone mineral density loss in patients with early spondyloarthritis.

OBJECTIVE: The aim of this study was to assess the effect of baseline inflammation on Magnetic Resonance Imaging (MRI) on the change in Bone Mineral Density (BMD) over 5 years in patients with early spondyloarthritis (SpA). METHODS: From the patients of the DESIR cohort (an early axial SpA cohort), patients with BMD data at both baseline and 5 years, and baseline spine and sacroiliac joints MRI were included. Inflammation was assessed with the SpondyloArthritis Research Consortium of Canada (SPARCC) spine score. Significant BMD loss was defined by a change of >0.03g/cm2. No patients had received TNF blockers before inclusion in the cohort. Univariate and multivariable prognostic analyses were performed. An inverse propensity score weighting method was used to handle confounders. RESULTS: One hundred and eighty-three patients were included (mean age 33.9±8.7 years, 58.5% men). A significant bone loss was reported in 51% (n=92) of patients at either lumbar spine or hip. Fourteen (7%) patients had low BMD (Z-score <-2) at the end of the follow-up vs. 28 (15%) at baseline. In multivariable analysis, age was a protective factor of 5 year-BMD loss at any site (OR=0.96, 95% CI [0.93-0.99]). Baseline MRI inflammation has no significant effect on BMD change at any site (OR=0.84, 95% CI [0.46-1.53]). CONCLUSION: Half of patients with early SpA have a significant bone loss at either lumbar spine or hip over 5 years. Baseline MRI inflammation is not a determinant of this bone loss.

Biologics in rheumatoid arthritis: where are we going?

Biological disease-modifying antirheumatic drugs have significantly improved outcomes for patients with rheumatoid arthritis, but cost limits their use. This article assesses data on patients who have achieved remission or low disease activity with these drugs and the possibility of dose reduction or discontinuation in these patients.

Certolizumab pegol in rheumatoid arthritis: current update.

INTRODUCTION: The development of TNF-α inhibitors (TNF-is) represents a major advancement in the treatment of rheumatoid arthritis (RA). Currently, there are five agents licensed for moderate-to-severely active RA. Certolizumab pegol (CZP) is a novel PEGylated, constant fragment-free TNF-i therapy, which is the focus of this review. AREAS COVERED: Data from Phase III randomised controlled trials in terms of clinical efficacy, radiographic progression, patient-reported outcomes and safety profile are reviewed. These include long-term data from open-label extension studies. EXPERT OPINION: The advantages of CZP include rapid reduction of disease activity, low rates of injection-site reaction and may be safe for use in pregnancy. The long-term data strengthen the position of CZP for use either as monotherapy or preferably in combination with disease modifying anti-rheumatic drugs (DMARDs), in moderate-to-severely active RA, comparable to other TNF-is. Notably, prolonged CZP exposure is not associated with increased risk of severe infection compared to general population, contrasting with preliminary analysis of short-term data. Over the next few years, evidence will be available on the use of CZP in combination with methotrexate for remission induction in DMARD-naïve patients, biomarkers and the development and licensing of TNF-i biosimilars.