Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study.

BACKGROUND: The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. OBJECTIVES: To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. METHODS: Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis-α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. RESULTS: We included 5468 biologic-naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25-p75) follow-up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16-3.21), 1.93 (1.05-3.34), 1.94 (1.09-3.32), 1.92 (0.93-3.45) and 1.43 (0.84-2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41-2.22); ustekinumab vs. adalimumab: 0.81 (0.30-2.17); etanercept vs. adalimumab: 0.81 (0.28-2.30)] and methotrexate against adalimumab [1.05 (0.34-3.28)]. CONCLUSIONS: In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow-up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.

Developing a foot ulcer risk model: what is needed to do this in a real-world primary care setting?

AIM: To determine how routinely collected data can inform a risk model to predict de novo foot ulcer presentation in the primary care setting. METHODS: Data were available on 15 727 individuals without foot ulcers and 1125 individuals with new foot ulcers over a 12-year follow-up in UK primary care. We examined known risk factors and added putative risk factors in our logistic model. RESULTS: People with foot ulcers were 4.2 years older (95% CI 3.1-5.2) than those without, and had higher HbA1c % (mean 7.9 ± 1.9 vs 7.5 ± 1.7) / HbA1c mmol/mol (63 ± 21 vs 59 ± 19) (p<0.0001) concentration [+0.45 (95% CI 0.33-0.56), creatinine level [+6.9 µmol/L (95% CI 4.1-9.8)] and Townsend score [+0.055 (95% CI 0.033-0.077)]. Absence of monofilament sensation was more common in people with foot ulcers (28% vs 21%; P<0.0001), as was absence of foot pulses (6.4% vs 4.8%; P=0.017). There was no difference between people with or without foot ulcers in smoking status, gender, history of stroke or foot deformity, although foot deformity was extremely rare (0.4% in people with foot ulcers, 0.6% in people without foot ulcers). Combining risk factors in a single logistic regression model gave modest predictive power, with an area under the receiver-operating characteristic curve of 0.65 (95% CI 0.62-0.67). The prevalence of ulceration in the bottom decile of risk was 1.8% and in the top decile it was 13.4% (compared with an overall prevalence of 6.5%); thus, the presence of all six risk factors gave a relative risk of 7.4 for development of a foot ulcer over 12 years. CONCLUSION: We have made some progress towards defining a variable set that can be used to create a foot ulcer prediction model. More accurate determination of foot deformity/pedal circulation in primary care may improve the predictive value of such a future risk model, as will identification of additional risk variables.

Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis.

BACKGROUND: Evidence of the comparative effectiveness of biological therapies for psoriasis on health-related quality of life (HRQoL) in routine clinical practice is limited. OBJECTIVES: To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL. METHODS: This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL-5D (EQ-5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ-5D utility score. RESULTS: In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ-5D improved from 18 (13-24) and 0·73 (0·69-0·80) at baseline to 2 (0-7) and 0·85 (0·69-1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ-5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ-5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ-5D improvement. CONCLUSIONS: In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL.

Motivational interviewing-based training enhances clinicians' skills and knowledge in psoriasis: findings from the Pso Well® study.

BACKGROUND: Psoriasis is a common long-term, immune-mediated skin condition associated with behavioural factors (e.g. smoking, excess alcohol, obesity), which increase the risk of psoriasis onset, flares and comorbidities. Motivational interviewing (MI) is an evidence-based approach to health-related behaviour change that has been used successfully for patients with long-term conditions. This study assessed change in clinicians' MI skills and psoriasis knowledge following Psoriasis and Wellbeing (Pso Well® ) training. OBJECTIVES: To investigate whether the Pso Well training intervention improves clinicians' MI skills and knowledge about psoriasis-related comorbidities and risk factors; and to explore the acceptability and feasibility of the Pso Well training content, delivery and evaluation. METHODS: Clinicians attended the 1-day training programme focused on MI skills development in the context of psoriasis. MI skills were assessed pre- and post-training using the Behaviour Change Counselling Index. Knowledge about psoriasis-related comorbidity and risk factors was assessed with a novel 22-point measure developed for the study. Interviews with clinicians were analysed qualitatively to identify perceptions about the feasibility and acceptability of the training. RESULTS: Sixty-one clinicians completed the training (35 dermatology nurses, 23 dermatologists and three primary-care clinicians). Clinicians' MI skills (P < 0·001) and knowledge (P < 0·001) increased significantly post-training. Clinicians found the training valuable and relevant to psoriasis management. CONCLUSIONS: Attendance at the Pso Well training resulted in improvements in clinicians' knowledge and skills to manage psoriasis holistically. Clinicians deemed the training itself and the assessment procedures used both feasible and acceptable. Future research should investigate how this training may influence patient outcomes.

Association of morbid obesity with disability in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Obesity has been associated with disease outcomes in inflammatory arthritis. This study aimed to investigate cross-sectionally the relationship between body mass index (BMI) and functional disability in a large inception cohort of patients with early inflammatory polyarthritis (IP). METHODS: Patients age ≥16 years with ≥2 swollen joints for ≥4 weeks were recruited into the Norfolk Arthritis Register. At the initial assessment, clinical and demographic data were obtained, joints were examined, and height and weight were measured. Blood samples were taken to measure inflammatory markers and autoantibodies, and patients completed the Health Assessment Questionnaire (HAQ) to assess functional disability. Univariate and multivariate ordinal regression were used to examine the cross-sectional association between BMI and the HAQ. Multiple imputation using chained equations allowed inclusion of patients with missing variables. RESULTS: A total of 1,246 patients were studied (median age 57 years). Of those patients, 782 patients (63%) were female and 303 (25%) were obese (BMI ≥30 kg/m(2) ). Morbid obesity (BMI ≥35 kg/m(2) ) was significantly associated with worse functional disability in the univariate and multivariate analysis with missing data imputed, adjusting for age, sex, symptom duration, smoking status, disease activity, autoantibodies, comorbidities, and treatment (multivariate odds ratio 1.87, 95% confidence interval 1.14-3.07). CONCLUSION: Morbid obesity in patients with early IP is associated with worse HAQ scores. This should be taken into account in patient management and when interpreting the HAQ in clinical practice.

Bone marrow lesions in knee osteoarthritis change in 6-12 weeks.

OBJECTIVES: Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage. METHODS: In 62 patients with patellofemoral knee OA (mean age 55.7 years, 59.7% women, mean BMI 31.0), we obtained baseline, 6 and 12 week knee MRIs with contrast enhancement. Of those with BMLs at baseline, we assessed BML volume on the axial proton density fat saturated (FS) images and postcontrast sagittal T1 weighted FS images. We manually segmented BML volumes, testing repeatability of BML volumes in knees remeasured. Using the standard deviation of the difference between repeated measurements to calculate Bland-Altman Limits of Agreement, we determined how much BML volume change represented a change greater than due to chance. RESULTS: Fifty-two patients had BMLs at baseline. Test-retest reliability for BML volume was high (ICC 0.89, 95% CI 0.80-0.97). All knees showed at least some change in BML volume by 6 and 12 weeks. On the axial view at 6 weeks, 20/49 (40.8%) knees showed BML volume changes greater than the limits of agreement with similar results at 12 weeks. BML changes were evenly divided among knees with enlarging and shrinking BMLs. 63.3% of the knees had more than 50% change in BML volume at either 6 or 12 weeks on the axial view and 48.7% on the sagittal view. CONCLUSIONS: Knee BML volumes change in several weeks in many persons with knee OA. To the extent that they could be regarded as treatment targets, trials testing BML effects could avoid the usual prolonged structure modification trials.

Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVES: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. RESULTS: 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.

Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.

OBJECTIVE: To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). METHODS: 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. RESULTS: 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. CONCLUSION: Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.

Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To explore the influence of anti-tumor necrosis factor (anti-TNF) therapy upon the incidence of cancer in patients with rheumatoid arthritis (RA) and prior malignancy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study established in 2001, we identified 293 patients with a prior malignancy from over 14,000 patients with RA. We compared rates of incident malignancy in 177 anti-TNF-treated patients and 117 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs), all with prior malignancy. One patient switched therapy and contributed to both cohorts. RESULTS: The rates of incident malignancy were 25.3 events/1,000 person-years in the anti-TNF cohort and 38.3/1,000 person-years in the DMARD cohort, generating an age- and sex-adjusted incidence rate ratio of 0.58 (95% confidence interval 0.23-1.43) for the anti-TNF-treated cohort compared with the DMARD cohort. Of the patients with prior melanomas, 3 (18%) of 17 in the anti-TNF cohort developed an incident malignancy, compared with 0 of 10 in the DMARD cohort. CONCLUSION: The way in which UK rheumatologists are selecting patients with RA and prior malignancy to receive anti-TNF therapy is not leading to an increased risk of incident malignancy. Although reassuring, these results should not be interpreted as indicating that it is safe to treat all RA patients with prior malignancy with anti-TNF therapy.

Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has been associated with reports of rapid severe progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, reports also exist of favourable responses to anti-TNF therapy in patients with ILD. The aim of this study was to examine the influence of anti-TNF therapy on mortality in patients with pre-existing RA-ILD. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, 367 patients with pre-existing RA-ILD were identified (299 treated with anti-TNF therapy and 68 treated with traditional disease-modifying antirheumatic drugs (DMARDs)). RESULTS: 70/299 patients (23%) in the anti-TNF cohort died after a median follow-up of 3.8 years compared with 14/68 (21%) in the DMARD cohort after a median follow-up of 2.1 years. The mortality was 68 deaths/1000 person years (pyrs) (95% CI 53 to 86) in the anti-TNF cohort and 92/1000 pyrs (95% CI 50 to 155) in the DMARD cohort, generating an age- and sex-adjusted mortality rate ratio (aMRR) of 1.26 (95% CI 0.69 to 2.31). After further adjustment for potential confounders, the aMRR fell to 0.81 (95% CI 0.38 to 1.73) for the anti-TNF cohort compared with the DMARD cohort. RA-ILD was the underlying cause of death in 15/70 (21%) and 1/14 (7%) patients in the anti-TNF and DMARD cohorts, respectively. CONCLUSION: The mortality in patients with RA-ILD is not increased following treatment with anti-TNF therapy compared with traditional DMARDs. The proportion of deaths attributable to RA-ILD is higher in patients treated with anti-TNF therapy, although reporting bias may exist.

Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR).

BACKGROUND: The risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA). OBJECTIVE: To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity. METHODS: Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs. RESULTS: To April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA (39/100,000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy. CONCLUSION: The rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.

Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis.

OBJECTIVE: To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, or carriage of shared epitope (SE) and PTPN22 genetic susceptibility variants predict response to therapy in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) agents. METHODS: UK-wide multicentre collaborations were established to recruit a large cohort of patients treated with anti-TNF drugs for RA. Serum RF, anti-CCP antibody and SE status were determined using commercially available kits. PTPN22 R620W genotyping was performed by Sequenom MassArray. Linear regression analyses were performed to investigate the role of these four factors in predicting response to treatment by 6 months, defined as the absolute change in 28-joint Disease Activity Score (DAS28). RESULTS: Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF and anti-CCP positive, respectively. Patients that were RF negative had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28 compared to patients that were RF positive. A better response was also seen among patients that were anti-CCP negative. No association was demonstrated between drug response and SE or PTPN22 620W carriage. CONCLUSION: The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs. However, these antibodies only account for a small proportion of the variance in treatment response. It is likely that genetic factors will contribute to treatment response, but these do not include the well established RA susceptibility loci, SE and PTPN22.

Association between duration of symptoms and severity of disease at first presentation to paediatric rheumatology: results from the Childhood Arthritis Prospective Study.

OBJECTIVES: To study the association between disease severity at first presentation to paediatric rheumatology (PRh) and length of time since symptom onset in children recruited to the Childhood Arthritis Prospective Study. METHODS: Children or=2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses. RESULTS: Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation. CONCLUSIONS: Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.

Effects of switching between anti-TNF therapies on HAQ response in patients who do not respond to their first anti-TNF drug.

OBJECTIVES: Small studies have shown an improvement in disease activity in patients with RA who have switched between anti-TNF therapies for reasons of inefficacy. However, it is not clear whether switching improves longer term outcomes, such as disability. This analysis compares changes in HAQ scores 1 yr following lack of response to a first anti-TNF based on subsequent treatment during that year. METHODS: Analysis was limited to RA patients with inefficacy to a first anti-TNF based on (i) clinician opinion and/or (ii) disease activity score in 28 joints and had an HAQ measured at time of non-response and 12 months later. Patients were classified into three groups based on treatment during the next 12 months: (i) continued anti-TNF despite non-response; (ii) stopped anti-TNF with no further biologics; and (iii) switched to a second anti-TNF. Mean improvement in HAQ was compared among the groups using multivariable linear regression models. RESULTS: As of July 2006, 868 patients met the inclusion for this analysis. Four hundred and seventy-nine patients stopped anti-TNF of whom 331 switched to a second anti-TNF. Three hundred and eighty-nine continued treatment. Patients who continued and those who switched had improvements in HAQ over the 12 months, unlike patients who discontinued all biologic therapy. The best improvement was seen in those who switched [adjusted mean improvement in HAQ 0.15 (95% CI 0.26, 0.05)]. CONCLUSION: There is a significant improvement in HAQ in patients who switch to a second anti-TNF, providing an effective next choice of therapy for some patients who fail to respond to their first anti-TNF.

Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs). RESULTS: Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69). CONCLUSION: These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.

Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies.

OBJECTIVE: In a recent observational study, we found that the risk of serious infection following anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection. METHODS: We compared the risk of serious infection in 8,659 patients treated with anti-TNFalpha with that in 2,170 patients treated with traditional disease-modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation. RESULTS: When the at-risk period was defined as "receiving treatment", the adjusted incidence rate ratio comparing patients receiving anti-TNFalpha therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88-1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8-11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation. CONCLUSION: These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti-TNFalpha therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.

Acculturation and the prevalence of pain amongst South Asian minority ethnic groups in the UK.

BACKGROUND: Musculoskeletal pain is reported more commonly by South Asians in the UK than by white Europeans. This may result from a variety of factors, including cultural differences, and thus we investigated the extent to which differences in the prevalence of pain within the South Asian population could be explained by differences in acculturation (the extent to which immigrants take on the culture of their host population). METHODS: Nine hundred and thirty-three Europeans and 1914 South Asian (1165 Indian, 401 Pakistani and 348 Bangladeshi) subjects were recruited from the age-sex registers of 13 general practices in areas with high densities of South Asian populations (Bolton, Oldham, Ashton-under-Lyne and Birmingham). A 28-item acculturation scale was developed, based, on aspects including use of language, clothing style, and use of own-culture media. Principle component analysis generated a score (range 0-100), which was validated against constructs expected to relate to acculturation, such as years of full time education and time spent in the UK. The presence of widespread pain was assessed by the answer to the question 'Have you suffered from pain all over the body in the past month?' RESULTS: Widespread pain was more common in all three South Asian ethnic groups than in the white Europeans [odds ratio (OR) = 3.7, 95% confidence interval (CI) 2.9-4.9], with this increase ranging from 2.7 to 5.8 in the different South Asian subgroups. There was a similar increase in consultation rates for pain. Within the South Asians, pooling all three groups, there was a strong negative association between acculturation score and widespread pain, which remained after adjusting for age and sex: [OR (95% CI) per standard deviation decrease in acculturation score -1.2 (1.0-1.3)]. Adjusting for acculturation accounted for some, but not all, of the differences between the ethnic groups in the prevalence of widespread pain: OR 2.0 (95% CI 1.4-3.0). CONCLUSIONS: Widespread pain is more commonly reported in South Asians though there are interesting differences within the South Asian community. Lower acculturation has a strong influence on the reporting of pain, but cannot explain all of the difference between South Asian and European populations.

Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype.

OBJECTIVES: We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. METHODS: We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. RESULTS: SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). CONCLUSIONS: SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.