Correction: Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

[This corrects the article DOI: 10.1371/journal.pone.0215999.].

Cervical screening uptake and rates of cervical dysplasia in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: To compare cervical screening attendance and cytology (high- and low-grade cervical dysplasia [HGCD and LGCD]) between women with RA and the English general population and between biologic DMARD (bDMARD)-naïve and exposed women. METHODS: The British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national prospective study of RA treatment outcomes, was linked to the National Health Service Cervical Screening Programme, providing data for 12 785 women to compare with national screening data. Rates of HGCD/LGCD were compared with rates of negative smears using risk difference calculations between BSRBR-RA and national statistics. Within the BSRBR-RA, coverage was compared between those with low and high physical disability scores, while coverage and cytology results were compared between bDMARD-naïve and -exposed RA patients. RESULTS: The mean 5 year screening coverage was significantly higher in BSRBR-RA (83%) compared with the general population (79%), but lower in women with high disability (78%) compared with lesser disability (85%). Risk differences for HGCD were lower in the BSRBR-RA compared with national statistics, whereas risk differences for LGCD were higher. There was no statistically significant difference in the rates of HGCD or LGCD between bDMARD-exposed and -naïve women. CONCLUSION: This first-ever British analysis of cervical screening rates in RA has shown that women with RA have higher screening rates than the general population. Disability negatively impacts attendance, but treatment type does not. Women with RA did not have an increased risk of HGCD compared with national statistics, which was also not influenced by bDMARD exposure.

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

BACKGROUND: United Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA. METHODS: The study included biologic-naïve patients receiving csDMARDs only with MDA (3.2

A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. RESULTS: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI -14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. CONCLUSION: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.

Systematic review of the predictors of statin adherence for the primary prevention of cardiovascular disease.

INTRODUCTION: Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention populations. Therefore the aim of this systematic review was to review predictors of statin adherence for the primary prevention of CVD. METHODS: A systematic search of papers published between Jan 1984 and May 2017 was conducted in PubMed, PsycINFO, EMbase and CINAHL databases. A study was eligible for inclusion if; 1) it was a study of the general population or of patients with familial hypercholesterolemia, hypertension, diabetes or arthritis; 2) statins were prescribed; 3) adherence was defined and measured as the extent to which patients followed their statin regimen during the period of prescription, and 4) it was an original trial or observational study (excluding case reports). A study was subsequently excluded if 1) results were not presented separately for primary prevention; 2) it was a trial of an intervention (for example patient education). Papers were reviewed by two researchers and consensus agreed with a third. A quality assessment (QA) tool was used to formally assess each included article. To evaluate the effect of predictors, data were quantitatively and qualitatively synthesised. RESULTS: In total 19 studies met the inclusion criteria and nine were evaluated as high quality using the QA tool. The proportion of patients classed as "adherent" ranged from 17.8% to 79.2%. Potential predictors of statin adherence included traditional risk factors for CVD such as age, being male, diabetes and hypertension. Income associated with adherence more strongly in men than women, and highly educated men were more likely and highly educated women less likely to be adherent. Alcohol misuse and high BMI associated with non-adherence. There was no association between polypharmacy and statin adherence. The evidence base for the effect of other lifestyle factors and health beliefs on statin adherence was limited. CONCLUSION: Current evidence suggests that patients with more traditional risk factors for CVD are more likely to be adherent to statins. The implications for future research are discussed.

Malignancy and mortality rates in patients with severe psoriatic arthritis requiring tumour-necrosis factor alpha inhibition: results from the British Society for Rheumatology Biologics Register.

Objective: The aim of this study was to compare the incidence of cancer and all-cause and cause-specific mortality rates among a cohort of patients with severe PsA receiving TNF inhibitor (TNFi) with those of the general UK population. Methods: Cancers and deaths were identified from the national cancer and the national death registers in patients with PsA included in the British Society for Rheumatology Biologics Register from start of TNFi until 31 December 2012. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated using published cancer and death rates for the general population. SIRs were calculated for both overall cancer risk and non-melanoma skin cancer. SMRs were calculated for (1) all-cause mortality, (2) death from malignancy and (3) death from circulatory disease. Gender-specific analyses were also performed. Results: Thirty-four cancers and 41 deaths among 709 patients were observed. The risk of malignancy overall was not increased (SIR 0.94; 95% CI: 0.65, 1.34). However, there was a significantly increased incidence of non-melanoma skin cancer (SIR 2.12; 95% CI: 1.19, 3.50). The all-cause mortality rate in our cohort was increased (SMR 1.56; CI: 1.12, 2.11). Death from malignancy was not increased, but death from coronary heart disease was increased (SMR 2.42; 95% CI: 1.11, 4.59). Conclusion: In our cohort of patients with severe PsA, the overall incidence of malignancy was similar to that of the general population, although the incidence of non-melanoma skin cancer was increased. All-cause mortality was significantly increased, in part due to excess of deaths attributed to coronary heart disease.

Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS).

BACKGROUND: Methotrexate (MTX) remains the disease-modifying anti-rheumatic drug of first choice in rheumatoid arthritis (RA) but response varies. Predicting non-response to MTX could enable earlier access to alternative or additional medications and control of disease progression. We aimed to identify baseline predictors of non-response to MTX and combine these into a prediction algorithm. METHODS: This study included patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre prospective observational study of patients with RA or undifferentiated polyarthritis, commencing MTX for the first time. Non-response to MTX at 6 months was defined as "no response" using the European League Against Rheumatism (EULAR) response criteria, discontinuation of MTX due to inefficacy or starting biologic therapy. The association of baseline demographic, clinical and psychosocial predictors with non-response was assessed using logistic regression. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. RESULTS: Of 1050 patients, 449 (43%) were classified as non-responders. Independent multivariable predictors of MTX non-response (OR (95% CI)) were rheumatoid factor (RF) negativity (0.62 (0.45, 0.86) for RF positivity versus negativity), higher Health Assessment Questionnaire score (1.64 (1.25, 2.15)), higher tender joint count (1.06 (1.02, 1.10)), lower Disease Activity score in 28 joints (0.29 (0.23, 0.39)) and higher Hospital Anxiety and Depression Scale anxiety score (1.07 (1.03, 1.12)). The optimism-corrected AUC was 0.74. CONCLUSIONS: This is the first model for MTX non-response to be developed in a large contemporary study of patients commencing MTX in which demographic, clinical and psychosocial predictors were considered. Patient anxiety was a predictor of non-response and could be addressed at treatment commencement.

Baseline patient reported outcomes are more consistent predictors of long-term functional disability than laboratory, imaging or joint count data in patients with early inflammatory arthritis: A systematic review.

OBJECTIVE: To assess baseline predictors of long-term functional disability in patients with inflammatory arthritis (IA). METHODS: We conducted a systematic review of the literature from 1990 to 2017 using MEDLINE and EMBASE. Studies were included if (i) they were prospective observational studies, (ii) all patients had IA with symptom duration ≤2 years at baseline, (iii) follow-up was at least 5 years, and (iv) baseline predictors of HAQ score at long-term follow-up (i.e., ≥5 years following baseline) were assessed. Information on the included studies and estimates of the association between baseline variables and long-term HAQ scores were extracted from the full manuscripts. RESULTS: Of 1037 abstracts identified by the search strategy, 37 met the inclusion/exclusion criteria and were included in the review. Older age at baseline and female gender were reported to be associated with higher long-term HAQ scores in the majority of studies assessing these relationships, as were higher baseline HAQ and greater pain scores (total patients included in analyses reporting significant associations/total number of patients analysed: age 9.8k/10.7k (91.6%); gender 9.9k/11.3k (87.4%); HAQ 4.0k/4.0k (99.0%); pain 2.8k/2.9k (93.6%)). Tender joint count, erythrocyte sedimentation rate (ESR) and DAS28 were also reported to predict long-term HAQ score; other disease activity measures were less consistent (tender joints 2.1k/2.5k (84.5%); erythrocyte sedimentation rate 1.6k/2.2k (72.3%); DAS28 888/1.1k (79.2%); swollen joints 684/2.6k (26.6%); C-reactive protein 279/510 (54.7%)). Rheumatoid factor (RF) and erosions were not useful predictors (RF 546/4.6k (11.9%); erosions 191/2.7k (7.0%)), whereas the results for anti-citrullinated protein antibody positivity were equivocal (ACPA 2.0k/3.8k (52.9%)). CONCLUSIONS: Baseline age, gender, HAQ and pain scores are associated with long-term disability and knowledge of these may aid the assessment of prognosis.

Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study.

BACKGROUND: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure. METHODS: Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks. RESULTS: A total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort. CONCLUSIONS: RF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.

Long-term persistence with rituximab in patients with rheumatoid arthritis.

Objectives: To investigate the long term persistence of rituximab (RTX) in a large observational RA cohort, investigate persistence of RTX when used as a first or second line biologic DMARD (bDMARD), to characterize subsequent bDMARD treatment following RTX. Methods: Patients with RA starting treatment with RTX (MabThera) between 2008 and 2011 were recruited into the British Society for Rheumatology Biologics Register for RA. Duration of RTX treatment over the first 4 years after initiation was estimated via Kaplan-Meier estimates and the reason for discontinuation was ascertained. Subsequent bDMARD use following RTX discontinuation was characterised. Treatment survival in bDMARD-naïve (first line RTX use) and experienced (second line RTX use) cohorts was described. Results: One thousand six hundred and twenty-nine patients were recruited (1371 bDMARD-experienced and 258 bDMARD-naïve). Sixty percent of the whole cohort remained on RTX after 4 years. Ineffectiveness (46%) and death (24%) were the most common reason for RTX discontinuation. RTX discontinuation was associated with RF negativity for the bDMARD-experienced cohort. Of those that discontinued RTX, 46% initiated treatment with another bDMARD, with tocilizumab being the most common. Conclusion: This large study of patients initiating RTX treatment for severe RA found that 60% persisted with treatment after 4 years. This study also identified that RTX is tolerated well when used as a first or second line bDMARD.

Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register.

BACKGROUND: Long-term effectiveness of tumour necrosis factor alpha inhibitors (TNFi) has mainly been explored in patients with rheumatoid arthritis (RA) and the data available on patients with psoriatic arthritis (PsA) includes limited follow-up. OBJECTIVE: Investigate long-term effectiveness of first TNFi in a PsA population by describing treatment persistence, identify factors associated with 5-year persistence and further investigate comparative long-term effectiveness of subsequent TNFi treatments through persistence to treatment. METHODS: Patients with a rheumatologist diagnosis of PsA receiving their first TNFi registered in the British Society for Rheumatology Biologics Register (BSRBR) (2002-2006) were included. Treatment at different time points was described and factors associated with 5-year treatment persistence were identified by logistic regression. Kaplan-Meier analysis was used to assess factors associated with persistence to first TNFi and subsequent TNFi treatments. RESULTS: At 5 years, 46.7% of patients were still on their initial TNFi treatment. Better 5 -year persistence was associated with male gender, use of etanercept or adalimumab rather than infliximab and absence of baseline comorbidity. Five-year persistence estimates (95% CI) of first, second and third TNFi were 53% (49% to 57%), 60% (43% to 57%) and 48% (36% to 59%), respectively. CONCLUSION: We found good long-term persistence of TNFi in this PsA population both for the first and subsequent TNFi treatments. The relationship between persistence and relevant clinical factors was not strong and demonstrates the difficulties in predicting outcome of TNFi treatment in PsA.

Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register.

OBJECTIVE: To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. METHODS: Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. RESULTS: In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI -23% to -10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). CONCLUSION: Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.

Serious infection risk after 1 year between patients with rheumatoid arthritis treated with rituximab or with a second TNFi after initial TNFi failure: results from The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Objectives: Both TNF inhibitors (TNFi) and rituximab (RTX), a B-cell depleting biologic, can disrupt the immune system in RA. RTX is licensed in Europe for use following TNFi failure. However, safety data on serious infections (SIs) are scarce for RTX in daily practice. This analysis aims to compare the risk of SIs in the first year after a switch to either TNFi or RTX in patients who have failed a first TNFi. Methods: This study included patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR-RA) who switched to either a second TNFi or RTX after failing a first TNFi. Patients were followed until first SI, treatment discontinuation, last recorded follow-up or the end of the first year after the switch, whichever came first. SI was defined as requiring hospitalization, intravenous antibiotics or resulting in death. The risk of first SI was compared between TNFi and RTX using Cox proportional hazard models adjusted using propensity scores using inverse probability of treatment weighting. Results: This analysis included 3419 TNFi and 1396 RTX patients contributing 2765 and 1224 person-years (pyrs), respectively. SI occurred in 164 (4.8%) TNFi and 81 (5.8%) RTX patients giving a crude rate of 59 and 66 SI/1000 pyrs, respectively. The adjusted hazard ratio for SI was 1.0 (95% CI: 0.7, 1.4). Conclusion: The risk of SIs was comparable over the first year of treatment between TNFi and RTX treatment in patients who had failed a single prior TNFi.

Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

OBJECTIVES: Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. METHODS: Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. RESULTS: 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). CONCLUSIONS: Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

Practical Management of Respiratory Comorbidities in Patients with Rheumatoid Arthritis.

Lung disease is one of the most common causes of extra-articular morbidity and mortality in patients with rheumatoid arthritis (RA). Development of pulmonary manifestations may be due to the systemic disease itself; to serious respiratory adverse events such as pneumonitis and infections secondary to therapy; or to lifestyle habits such as smoking. Rheumatologists often need to make important treatment decisions and plan future care in RA patients with respiratory comorbidities, despite the absence of clear evidence or consensus. In this review we evaluate the clinical assessment and management of RA-associated interstitial lung disease, bronchiectasis, serious (including opportunistic) infection, and smoking-related diseases. We summarize the international recommendations for the management of such conditions where available, refer to published best practice on the basis of scientific literature, and propose practical management suggestions to aid informed decision-making.

Predictors of and outcomes following orthopaedic joint surgery in patients with early rheumatoid arthritis followed for 20 years.

Objectives: To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Methods: Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Results: Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [ß = 0.17 (95% CI 0.03, 0.32)]. Conclusion: HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.

Twenty-Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results From the Norfolk Arthritis Register.

OBJECTIVE: To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up. METHODS: Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring. RESULTS: This study included 602 patients with RA (median age 56 years [interquartile range 44-68 years]; 65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3 swollen joints and 3-6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow-up period (ß = 0.03, 95% confidence interval [95% CI] -0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, ß = 0.10 [95% CI 0.02, 0.17]). CONCLUSION: The results of this study indicate the importance of early treatment with regard to the long-term outcomes in patients with RA.

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). METHODS: This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression. RESULTS: 252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups. CONCLUSIONS: Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control.