Risks of smoking and benefits of smoking cessation on hospitalisations for cardiovascular events and respiratory infection in patients with rheumatoid arthritis: a retrospective cohort study using the Clinical Practice Research Datalink.

Objectives: To investigate the associations between smoking status, smoking cessation and hospitalisations for cardiovascular events (CVE) and respiratory tract infections (RTI) in an inception cohort of patients with rheumatoid arthritis (RA).

Methods: The study was set within UK primary care electronic health records (the Clinical Practice Research Datalink) linked to hospital inpatient data (Hospital Episode Statistics). Patients with RA were followed from diagnosis to hospitalisation with a record of CVE or RTI, leaving their general practice, death, or 10 January 2012, whichever was earliest.

Drug-specific risk and characteristics of lupus and vasculitis-like events in patients with rheumatoid arthritis treated with TNFi: results from BSRBR-RA.

Objective: To compare the risk of lupus-like events (LLEs) and vasculitis-like events (VLEs) in tumour necrosis factor-α inhibitor (TNFi)-treated patients with rheumatoid arthritis (RA) to those receiving non-biological disease-modifying antirheumatic drugs (nbDMARDs).

Methods: Patients were recruited to the British Society for Rheumatology Biologics Register-RA, a national prospective cohort study. Two cohorts recruited between 2001 and 2015: (1) patients starting first TNFi (adalimumab, etanercept, infliximab and certolizumab) (n=12 937) and (2) biological-naïve comparison cohort receiving nbDMARDs (n=3673).

Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis.

Objectives: Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs).

Use and effectiveness of tocilizumab among patients with rheumatoid arthritis: an observational study from the British Society for Rheumatology Biologics Register for rheumatoid arthritis.

The aims of the present study are to describe the characteristics of rheumatoid arthritis (RA) patients selected for tocilizumab (TCZ), compare the "real-world" effectiveness of TCZ and tumour necrosis factor inhibitors (TNFi) when used as a first biologic and assess the influence of past biologic exposure/concurrent methotrexate (MTX) therapy on post-TCZ treatment outcomes. The British Society for Rheumatology Biologics Register (BSRBR-RA) is a prospective cohort study following RA patients starting biologics in the UK. This includes patients starting TCZ as first or subsequent biologic, alongside biologic-naïve patients starting TNFi.

Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se: a multicenter cohort study.

Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies.

Effectiveness and safety of TNF inhibitors in adults with juvenile idiopathic arthritis.

Introduction: Many children with juvenile idiopathic arthritis (JIA) continue to have active disease into adulthood. Adults with JIA are a heterogeneous group, and the effects of tumour necrosis factor inhibitor (TNFi) therapies are not well described. This analysis aims to describe treatment outcomes among patients with JIA starting TNFi for the first time in adulthood.

HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis.

Objective: Rheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes.

Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis.

Objective: Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte-driven inflammation through a transforming growth factor β1-dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis.

Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink.

Objective: To investigate the association between smoking status and smoking cessation with mortality in patients with rheumatoid arthritis (RA).

Methods: An incident cohort of patients with RA was identified using the Clinical Practice Research Datalink, a database of UK primary care electronic medical records. Time-varying smoking status, years of cessation, and amount smoked were determined from patients' medical records.

The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Objective: To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy.

Methods: The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort.

Risk of lymphoma in patients exposed to antitumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Objectives: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation.

Cardiovascular risk and its modification in patients with connective tissue diseases.

It is well documented that patients with systemic lupus erythematosus (SLE) are at an increased risk of atherosclerotic cardiovascular (CV) disease. There is evidence that traditional risk factors and disease-related factors are involved in this increased risk. Less is known about CV risk and outcomes in other connective tissue diseases (CTDs).

Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

Objectives: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP.

Methods: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5.

Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis.

Objective: Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30-day and 1-year mortality after ischemic stroke.

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register.

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years' follow-up in a cohort of patients with inflammatory polyarthritis (IP).

Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009.

Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries.

Objective: Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries.

Methods: Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared.

Epidemiology research in rheumatology-progress and pitfalls.

Epidemiology research is a vital component of clinical studies in all medical fields. This Review provides a brief introduction to the methodology and interpretation of population and clinical epidemiology studies of musculoskeletal disorders. Data sources (including 'big data' and the issue of missing data), study design (cross-sectional, case-control and cohort studies, including clinical trial design) and the interpretation of study results are discussed with examples from the field of rheumatology, particularly using findings in patients with rheumatoid arthritis.

The influence of behavioural and psychological factors on medication adherence over time in rheumatoid arthritis patients: a study in the biologics era.

Objectives: To investigate levels of self-reported adherence to biologic treatment and establish the contribution of demographic, physical and psychological factors to biologic medication adherence in an RA cohort.

Methods: Adalimumab-treated patients were recruited through the British Society for Rheumatology Biologics Register for RA between May 2007 and April 2009. Demographic and baseline psychological measures including illness and medication beliefs were collected.

Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response.

Importance: Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response.

Objective: To assess whether specific HLA-DRB1 haplotypes associated with rheumatoid arthritis (RA) susceptibility are also associated with radiological severity, mortality, and response to tumor necrosis factor (TNF) inhibitor drugs.

Design, Setting, And Participants: The Norfolk Arthritis Register (NOAR; 1691 patients and 2811 radiographs; recruitment: 1989-2008; 2008 as final follow-up) was used as a discovery cohort and the Early Rheumatoid Arthritis Study (421 patients and 3758 radiographs; recruitment: 1986-1999; 2005 as final follow-up) as an independent replication cohort for studies of radiographic outcome.