Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept.

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS).

Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi.

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis.

Objective: To evaluate the longterm efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD).

Methods: Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD. After a 24-week double-blind period, patients (n = 457) were rerandomized to open-label TCZ-SC q2w by means of prefilled syringe or autoinjector.

Comparative effectiveness of treatment with the first TNF antagonist in monotherapy, the first TNF antagonist plus one conventional synthetic disease-modifying antirheumatic drug, and the first TNF antagonist plus two or more conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus, they are treated with the first TNF antagonists in monotherapy.

Association between serum dickkopf-1 levels and disease duration in axial spondyloarthritis.

Background: Axial spondyloarthritis (axSpA) is characterized by new bone formation. The complex systems underlying this process involve Wnt-signaling pathway. It has been observed that serum levels of dickkopf-1 (DKK-1), an important inhibitor of Wnt-signaling, are decreased in patients with axSpA.

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi.

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

Introduction: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA).

Methods: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients.

FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors.

Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other FcγR functional polymorphisms.

Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up.

MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study.

Objective: To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy.

Methods: Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52.

Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

Objective: The efficacy and safety of subcutaneous tocilizumab (TCZ-SC) versus subcutaneous placebo (PBO-SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs in the BREVACTA study.

Methods: Patients (n = 656) were randomized 2:1 to receive TCZ-SC 162 mg every other week or PBO-SC every other week for 24 weeks; 20% previously received anti-tumor necrosis factor treatment. Escape therapy with TCZ-SC 162 mg weekly was offered from week 12 for inadequate response.

Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis.

Objectives: We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF).

Methods: A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria.

Practice guidelines for the use of subcutaneous abatacept.

Objective: To review the clinical evidence on subcutaneous (sc) abatacept and to formulate recommendations in order to clear up points related to its use in rheumatology.

Method: An expert panel of rheumatologists objectively summarized the evidence on the mechanism of action, practicality, effectiveness, and safety of abatacept sc and formulated recommendations after a literature review.

Results: The efficacy and safety of abatacept sc was studied in 7 clinical trials, 3 double-blind, 3 open, and one mixed, with the following endpoints: comparison against abatacept iv, impact on immunogenicity, effect of replacing iv by sc, abatacept sc in monotherapy, and non-inferiority to adalimumab.

[Economic evaluation of rheumathoid arthritis monotherapy with tocilizumab and adalimumab].

Background: Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy, in reducing signs and symptoms of adult rheumatoid arthritis (RA) when methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the study was to analyze the cost-effectiveness of TCZ vs ADA in these patients.

Methods: Economic evaluation of the cost per response or remission of TCZ vs ADA from ADACTA (time horizon: 24 weeks).

A comparison of telephone and paper self-completed questionnaires of main patient-related outcome measures in patients with ankylosing spondylitis and psoriatic arthritis.

A cross-sectional study was performed to assess the correlation between telephone and self-administration of patient-related outcomes (PROs) used in the assessment of ankylosing spondylitis (AS) patients. Participants underwent a telephone interview in which the following measures were evaluated: numerical rating scales (NRSs) for global health, pain intensity, global pain, back pain, and back pain at night; BASDI, BASFI, Health Assessment Questionnaire (HAQ), ASQoL, EuroQol, SF-12, and Work Productivity and Activity Impairment (WPAI) questionnaire. Within 48 h after the telephone interview, patients were appointed for a clinical visit in which the same questionnaires and in the same order were self-administered.

Interaction between oxidative stress and smoking is associated with an increased risk of rheumatoid arthritis: a case-control study.

Objective: To investigate the relationship between oxidative stress and smoking and development of RA.

Methods: A case-control study was conducted in treatment-naïve early-onset RA patients and healthy controls, matched by age, gender and current smoking habit. Plasma lipid hydroperoxides (LOOH), carbonyl protein (CP) and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress.

Abatacept use in rheumatoid arthritis: evidence review and recommendations.

Objective: To review the clinical evidence on abatacept and to formulate recommendations in order to clear up points related to its use in rheumatology.

Method: An expert panel of rheumatologists objectively summarized the evidence on the mechanism of action, practicalities, effectiveness and safety of abatacept, and formulated recommendations following a literature review. The level of evidence and degree of recommendation was established.

Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY).

Objective: In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy.

Methods: Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO).

[Vaccines and chemo-prophylaxis in rhemautoid arthritis: is a vaccine calendar necessary?].

Patients with rheumatoid arthritis (RA) are at increased risk of infection compared to healthy individuals. The increased risk may be associated with the underlying disease, comorbidities and immunosuppressive therapy required to control RA activity. In several recent studies, influenza, pneumococcal and hepatitis B vaccines administered to RA patients were reported to be safe and serologically effective.

A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

Objective: AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular Adant) was designed to compare against placebo the efficacy and safety of repeated injections of hyaluronic acid (HA) and its effect on disease progression over 40 months.

Methods: A multicentre, randomised, patient and evaluator-blinded, controlled study in 306 patients fulfilling American College of Rheumatology criteria for knee osteoarthritis, radiological grades II-III (Kellgren-Lawrence) and joint space width ≥ 2 mm. Patients received four cycles of five intra-articular HA or placebo injections with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles.

High-dose etanercept in ankylosing spondylitis: results of a 12-week randomized, double blind, controlled multicentre study (LOADET study).

Objectives: Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS.

Low doses of etanercept can be effective in ankylosing spondylitis patients who achieve remission of the disease.

This study aims to explore the effectiveness of low dose of etanercept (ETN) in patients with ankylosing spondylitis (AS) who achieve a good control of their disease in daily clinical practice. This is a case series of AS patients treated with ETN. According to the judgment of the treating rheumatologist and patient's preferences, a dose reduction was done in those patients who achieved a good control of their disease defined by Bath ankylosing spondylitis disease activity index (BASDAI) <4 and C-reactive protein normal values.

DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists.

Introduction: No definitive data are available regarding the value of switching to an alternative TNF antagonist in rheumatoid arthritis patients who fail to respond to the first one. The aim of this study was to evaluate treatment response in a clinical setting based on HAQ improvement and EULAR response criteria in RA patients who were switched to a second or a third TNF antagonist due to failure with the first one.

Methods: This was an observational, prospective study of a cohort of 417 RA patients treated with TNF antagonists in three university hospitals in Spain between January 1999 and December 2005.

Variables related to utility in patients with ankylosing spondylitis.

The objective of this study was to identify variables associated to the utility of the health states in patients with ankylosing spondylitis (AS). A cross-sectional study was performed in a tertiary care centre. AS patients (New York modified criteria) were included.

[A bibliometric approach to research into fibromyalgia].

Objectives: To obtain a general and updated vision of research into fibromyalgia for its better understanding. A productivity analysis (by year and author) and a content analysis (by journal and topic) was carried out.

Methodology: The computer databases of the Web of Knowledge: Science Citation Index Expanded (SCIEXPANDED) and Social Sciences Citation Index (SSCI) of the Web of Science were used.