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Objective. To test the hypothesis that microvascular vasodilation is impaired in patients with systemic sclerosis (SSc) compared with patients with primary Raynaud’s phenomenon (PRP) and healthy controls, using the technique of laser Doppler imaging to quantify blood flow responses to iontophoresis of vasoactive agents. Methods. Microvascular blood flow was measured by laser Doppler imaging before, during and after 120 s iontophoresis (30lA) of 1% acetylcholine chloride (ACh, endothelium-dependent) and 1% sodium nitroprusside (NaNP, endotheliumindependent). Two adjacent fingers of the left hand were studied, and the procedure then repeated on the right. Ten patients with limited cutaneous SSc (LCSSc), 10 patients with PRP and 11 healthy control subjects were studied. Results. Vasodilation in response to both ACh and NaNP iontophoresis, as measured by ‘area under the blood flow.time curve’ (AUC), normalized for baseline flux, was similar in the control and PRP groups, but was diminished in the LCSSc group compared with both control and PRP groups (ACh results: control vs LCSSc P ¼ 0.028, PRP vs LCSSc P ¼ 0.005; NaNP results: control vs LCSSc P ¼ 0.004, PRP vs LCSSc P ¼ 0.005). There were no differences between groups in baseline flux values nor in voltages required to drive the 30lA current. Conclusions. Both endothelium-dependent and endothelium-independent vasodilation are impaired in patients with LCSSc. Vasodilatory responses in patients with PRP are similar to those in controls. If reproducibility is confirmed to be satisfactory, then these techniques could be used to examine disease progression over time and responsiveness to vasoactive treatment, thus facilitating clinical trials.

Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR] = 1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR = 1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR = 3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR = 1.2; 95% CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR = 1.6; 95% CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.

The aim of this study was to determine the contribution of constitutional and lifestyle variables on the subsequent risk of distal forearm (Colles') fracture in a multinational, multicenter, population-prospective study. A total of 15,745 subjects from the European Vertebral Osteoporosis Study, who had completed a baseline questionnaire on lifestyle and constitutional factors, were followed up annually using a validated questionnaire to ascertain the occurrence of new fractures. Risks are expressed as hazard ratios (with 95% confidence intervals) derived from a Cox proportional hazards regression model. The incidence of Colles' fracture was 1.7 and 7.3 per 1000 person years in men and women, respectively. In women delayed menarche, over the age of 15 years, was associated with a modest increased risk [HR 1.5 (range 1.1-2.0)]. Regular walking in that group also increased the risk [HR 1.6 (1.2-2.2)] perhaps reflecting the increased exposure to risk of falling. None of the other factors examined revealed any important influences. The results are broadly in line with the few other published prospective studies suggesting only a modest role for these factors in influencing susceptibility to fracture.

OBJECTIVES: To estimate the incidence of severe lung disease in patients with scleroderma and identify the combination(s) of features present at first assessment which would be useful to predict future risk of severe lung disease. METHODS: Data were analysed on 561 patients with disease onset occurring on or after 1 January 1982 and disease duration of less than five years before the first assessment. Detailed clinical and laboratory assessments were undertaken at the initial visit. End stage lung disease was defined as pulmonary hypertension requiring continuous ambulatory iloprost, or pulmonary fibrosis requiring continuous oxygen, or death from a scleroderma related lung disease. Patient status was determined at 31 December 1997. The best subset of predictors was identified by Cox regression analysis. RESULTS: In all, 24 patients reached end stage lung disease. The cumulative incidences were 4%, 6%, and 12% at five, seven, and 14 years respectively. As expected, the lung function tests at baseline, including being in the lowest third of either diffusing lung capacity (hazard ratio (HR) = 18.2, 95% confidence interval (CI) 3.5 to 93.8) or of forced vital capacity (HR=4.1, 95% CI 1.1 to 15.2), were highly significant predictors of end stage lung disease. Interestingly, apart from the presence of proteinuria, none of the other baseline variables, including the extent of skin disease and serological markers, were predictive of severe lung disease. CONCLUSION: End stage lung disease was infrequent in this large cohort, but the cumulative incidence increased importantly with time. The risk can be predicted from baseline assessment of pulmonary function. In particular, those with normal pulmonary function at baseline are at very low risk

Objective To determine the effect of early treatment with disease-modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5-year period in patients with new-onset inflammatory polyarthritis. Methods Three hundred thirty-five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population-based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, 12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5-year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling. Results Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD-treated patients compared with untreated patients, were as follows: 1.6 (1.1–2.3) for 12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8–1.7) for 12 months. This effect was also seen in the crude Larsen score at year 5. Conclusion In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.

Background: There is a wide variation in responses to standard disease modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Whether multidrug resistance, failure to respond to several DMARDs, is a specific entity over and above that expected by chance alone is unclear. Objective: To identify patients with RA who demonstrate a multidrug resistant phenotype and to determine what proportion of the variance in drug responses is due to patient related factors. Methods: Patients with RA (1987 American College of Rheumatology criteria) were identified from clinics at Manchester Royal Infirmary and through the Arthritis Research Campaign National RA Repository. The clinic records were reviewed and multidrug resistance was defined as stopping three or more DMARDs owing to lack of efficacy after an adequate trial of the drug. Logistic regression measured by a random effects model was used to determine the relative contribution of the drug and subject related differences to the multidrug resistance. Results: 265 patients (210 (79.3%) female) were studied. The mean (SD) age and disease duration were 52.2 (12.9) and 10.7 (8.8) years, respectively. Patients had a median (range) of 2 (1–8) DMARD courses. Failure of at least one DMARD due to inefficacy occurred in 105 (40%) and 13 (5%) were multidrug resistant. Overall, 35% of the variance in drug responses was due to between-subject differences (p=0.02). Rheumatoid factor (RF) status contributed significantly to this (OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained only 3% of the total variance in drug inefficacy. Conclusion: Multidrug resistance occurs in an uncommon (5%) but important subgroup of patients with RA. The between-subject variance is not fully explained by demographics and RF status. Understanding the biological mechanisms that contribute to multidrug resistance may suggest new therapeutic approaches and targets in RA.

The purpose of this study was to compare hip bone mineral density (BMD) recorded in seven population based cohorts in Britain with the third National Health and Nutrition Examination Survey (NHANES III) US population-based reference data, in order to assess geographic variation in the prevalence of osteoporosis. Men and women aged 50-80+ years were randomly recruited from population and health registers. Dual X-ray absorptiometry (DXA) equipment was used to measure BMD at the hip, with the femoral neck and the trochanter regions studied. Prevalences of osteopenia and osteoporosis were estimated in accordance with World Health Organisation diagnostic criteria for women. Young normal data, used to establish cut-off criteria, was from NHANES III. Both male and female British subjects over 50-years-old were found to have significantly higher mean BMD at the femoral neck and trochanter than their US counterparts. Decline in BMD with age in British men appeared slower than in US men. Between British centres there were also statistically significant differences in BMD values in both sexes. British age-adjusted prevalences of osteopenia in women averaged 20% less than those of NHANES III, whereas the prevalence of osteoporosis was substantially lower in British subjects of both sexes (55% in women, 68% in men). Thus, applying the US NHANES III data as the referent, osteoporosis of the proximal femur in Britain appears to be less common than in the US, due primarily to differences in the lower tails of the BMD distributions. Providing that the relationship between fracture rates and BMD is the same in Britain and the US, it would still be appropriate to apply the reference data in fracture risk assessment in the UK.

In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6–12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p

The study assessed the precision, sensitivity, and specificity of a recently developed peripheral dual-energy X-ray absorptiometry (DXA) scanner, applied to the calcaneus, in the identification of individuals with osteoporosis at axial sites by DXA. Two hundred and two women, aged 55.2 +/- l3.7 years (mean +/- SD), participated in the study. The precisions (coefficient of variation) of measurements in vitro (0.48%) and in vivo (1.40%) were very good. The in vivo precision was independent of the operator, foot size, foot width, weight, height, and body mass index. Calcaneus BMD correlated moderately (r = 0.494-0.690, P

Objective To identify the relative contributions of clinical and laboratory variables, determined at baseline, in predicting the deterioration of radiographic damage 5 years after presentation in patients with inflammatory polyarthritis. Methods Data from 439 subjects who sought primary care for inflammatory polyarthritis were analyzed. All subjects had paired radiographs, of which the first was obtained within 24 months of presentation and the second at 5 years after presentation. The contribution of baseline clinical and laboratory variables in predicting the degree of radiologic severity as judged by the Larsen score was assessed at both time points. Additionally, the role of these factors in predicting change after adjustment for baseline severity was also measured. Results By 5 years, 49% of subjects had evidence of erosions. The median Larsen score on the first film was 2 (interquartile range [IQR] 0–10) and the median score on the followup film was 7 (IQR 1–25). These corresponded to a median deterioration of 3 (IQR 0–14) in all subjects, whereas those subjects with evidence of erosions at first film showed a median deterioration of 15 (IQR 6–29) on followup. The rheumatoid factor (RF) status, C-reactive protein levels, the presence of nodules, and number of swollen joints at baseline were all predictive of radiographic severity at first film. Not surprisingly, the baseline radiographic score was a predictor of severity of deterioration. However, after adjusting for baseline severity, a high titer of RF (>1:160) was also an independent predictor of deterioration over 5 years: individuals with an initial RF at that level had a progression in their Larsen score that was 2.3 times (95% confidence interval 1.7–3.2) higher than that in the RF-negative individuals. Apart from this, only age had an independent effect, after adjusting for baseline severity, in predicting increasing radiographic joint damage. Conclusion High-titer RF is an important variable in predicting continuing severity of radiographic damage during the first 5 years after presentation with inflammatory polyarthritis.

Background and aims. Symmetry is considered an important criterion for the differentiation of rheumatoid arthritis (RA) from other forms of inflammatory polyarthritis (IP), particularly those that are seronegative. Because of the inclusion of symmetry in the diagnostic and classification process, however, its true occurrence in RA cannot be assessed. As a surrogate, peripheral inflammatory arthropathies associated with rheumatoid factor production may be more likely to be symmetrical. We examined the degree of symmetry of erosions in an unselected cohort of patients with IP and tested the hypothesis that the presence of rheumatoid factor (RF) is associated with greater symmetry. Methods. All patients registered with The Norfolk Arthritis Register (NOAR; a UK primary-care based cohort of patients with IP with annual follow-up) and who had radiographs performed at the fifth anniversary from notification were included in the analysis. Radiographs of the hands and feet were read using the Larsen method; a score of 2 or more in any particular joint indicated an erosion. Log-linear modelling was used to determine the symmetry of erosions between right and left for the following joint groups: wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints. Log-linear modelling was also used to determine the influence of RF on symmetry. Results. Five hundred and thirty-seven patients contributed to the analysis. The median time to performing radiographs was 69 months (interquartile range 65.5 ‐74.8) from the onset of symptoms. A total of 212 (39%) patients had erosive disease. Overall, IP was found to be a symmetrical disease. Despite there being more erosions in RF-positive patients, there was no greater excess of symmetry in RF-positive compared with RF-negative patients. Conclusion. Radiographically, IP is a symmetrical disease irrespective of RF status. The use of symmetry as an important feature in identifying subgroups of patients with IP, such as RA, is challenged.

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX ‘beta’ versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p

Objective\ud \ud The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK.\ud \ud Methods\ud \ud Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership.\ud \ud Results\ud \ud The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression.\ud \ud Conclusion\ud \ud Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.

Objective.To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years.Methods.NOAR is a primary-care–based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990–1994; Cohort 2: 1995–1999; Cohort 3: 2000–2004; Cohort 4: 2005–2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity.Results.A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (–0.56 × year) + (0.44 × year2)]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year2)]. Similar results were observed in each subpopulation of patients.Conclusion.While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.

OBJECTIVES: Children with JIA can experience delayed and restricted growth. The objectives of this study were to investigate the influence of etanercept (ETN) on vertical growth and factors associated with improved growth in patients with JIA over the initial 2 years of treatment. METHODS: This analysis was restricted to ETN-treated patients in the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study with complete height data recorded at baseline, 1 and 2 years. Height z-scores were calculated using the World Health Organization growth standards for age and gender. Change in height z-score was evaluated over time. Multivariable linear regression was used to identify factors associated with change in height z-score from baseline. RESULTS: A total of 191 ETN-treated patients were included: 65% female, median baseline age 11.0 years [interquartile range (IQR) 7.3-12.9], median disease duration 3.5 years (IQR 1.7-7.1). At baseline mean height z-score was -0.74 (s.d. 1.4). After 2 years mean height z-score increased to -0.45 (1.4) (change +0.29; P < 0.001). In multivariable analysis, factors associated with an improvement in height z-score included lower baseline height z-score [-0.110 per unit (95% CI -0.161, -0.059), P < 0.001] and no oral corticosteroid use at baseline [-0.192 (95% CI -0.343, -0.040), P = 0.013]. CONCLUSION: ETN therapy was associated with an improvement in height z-score over the first 2 years of therapy in this real-world cohort of children with severe JIA. The lack of a strong association of improvements in height with improvements in disease activity warrants further exploration.

Importance There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. Objective To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. Data Sources Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. Study Selection Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. Data Extraction and Synthesis Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. Main Outcome and Measures Change in self-reported knee pain at follow-up. Results Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, −0.47; 95% CI, −0.80 to −0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of −2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, −1.20 [95% CI, −2.09 to −0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, −0.03 [95% CI, −0.18 to 0.12] on WOMAC; this represents an effect of −0.12 points), and results showed little heterogeneity (I2 = 7.1%). Conclusions and Relevance Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication.

Incident vertebral deformities are commonly defined by observed changes in height between measurements on two consecutive radiographs. However, conventional radiographs are subject to magnification, and this magnification may differ between films, leading to artifactual changes in height. In order to minimize this effect, it is common practice to record the spine-film and film-focus distances, and from this to calculate a magnification factor for each film. We present a simple statistical method for correcting for differences in magnification between two films if the spine-film and film-focus distances are unknown. This method is shown to reduce the variance of the magnification differences in vertebral heights by 14%, considerably more than is possible using the spine-film distance. Using the statistical method, the number of vertebrae that showed not only a reduction in one or more height of 15%, but were also judged clinically to be free from any incident deformity by an expert radiologist, was reduced from 100 to 46. The number showing a reduction of 20% that were judged fracture-free was reduced from 15 to 9. In the subset of subjects for whom the spine-film distance was known, the reduction in false positives was similar, whichever method was used to correct for magnification. There was no difference in the number of confirmed incident fractures detected when magnification correction by either method was employed. It is concluded that correcting for magnification differences using the statistical method outlined here reduces the number of false positive deformities very substantially and by a similar extent as correcting the magnification using reliable, measured spine-film and film-focus distances. A further advantage of this method is that it can be used retrospectively.

Objective To examine the time of occurrence of first radiographic erosions in a cohort of patients with inflammatory polyarthritis. Methods Patients were recruited through the Norfolk Arthritis Register, which follows up patients annually. Patients with features of rheumatoid arthritis (other than erosions) sufficient, together with erosions, to meet the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 revised criteria were requested to undergo radiographic examinations of the hands and feet at the first and/or second annual followup visits. All patients were requested to undergo radiographic examinations at the fifth annual followup visit. The most recent erosion-free radiograph was identified for 416 eligible patients, and these data were used to derive the duration of disease since the recalled date of onset of first symptoms. The rate of occurrence of first erosions was then determined (as a cumulative prevalence and as an incidence rate using Poisson regression) from analysis of followup films. Patients were assumed to be free of erosions at symptom onset. Results The cumulative prevalence of erosions in patients whose first film was obtained 12–24 months after disease onset was 36%, equivalent to an incidence rate of 24.5/1,000 patient-months. We identified 3 analysis groups of patients who were free of erosions based on films obtained 12–24 months, 24–36 months, and 36–60 months since the recalled date of onset of first symptoms. New erosions were observed in all 3 groups, with cumulative prevalences of 23%, 28%, and 47%, respectively. These were equivalent to first-erosion incidence rates/1,000 patient-months of 5.4 (95% confidence interval [95% CI] 3.8–8.3), 6.8 (95% CI 4.7–10.0), and 13.0 (95% CI 8.9–19.2), respectively. Conclusion Many patients with erosive disease first develop their erosions >2 years from disease onset.

Objective To determine the effect of treatment with disease-modifying antirheumatic drugs (DMARDs) and/or steroids on 5-year disability outcome in patients with inflammatory polyarthritis. Methods Three hundred eighty-four patients registered by the Norfolk Arthritis Register (a primary care–based observational cohort) were followed up for 5 years. Treatment details and Health Assessment Questionnaire (HAQ) scores were recorded annually. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs and/or steroids within 12 months of baseline. Based on this model, each subject was given a probability of starting treatment (“propensity score”). A second model compared the odds of disability (HAQ score ≥1.00) in treated and untreated patients, adjusting for differences in disease severity using the propensity score. Results Unadjusted analysis suggested that patients who received treatment had an increased odds of a worse outcome compared with those who did not receive treatment. When adjusted for differences in disease severity, using the propensity score, early treatment (within 6 months of symptom onset) was associated with a similar odds of disability at 5 years compared with those not treated (odds ratio 0.71; 95% confidence interval 0.34, 1.44). In contrast, starting treatment later (≥6 months) was associated with a 2-fold increased odds of having a HAQ score ≥1.00 at 5 years. Conclusion The propensity score was a useful method of adjusting for “confounding by indication” in observational studies. Furthermore, this study showed that early treatment with DMARDs/steroids (within 6 months of symptom onset) reduced the odds of disability 5 years later to a level comparable with that of patients judged clinically as not requiring treatment.

Background : Previous reports suggest a possible increased risk of osteoporosis in those with postmenopausal symptoms. There are, however, no data from population samples, exploring the relationship between postmenopausal symptoms and vertebral osteoporosis. Aim : To determine if there is an association between self-reported postmenopausal symptoms and radiographic vertebral deformity. Methods : Women aged 50 years and over were recruited from population registers in 30 European centres and invited to attend for an interviewer administered questionnaire and lateral thoracic and lumbar spine radiographs. The questionnaire sought information about aspects of lifestyle, personal, medical and gynaecological history, including postmenopausal symptoms: flushing, sleep disturbance and ‘other’ symptoms. Radiographs were taken according to a standard protocol and evaluated morphometrically. Vertebral deformity was defined according to the McCloskey–Kanis method. Bone mineral density data were obtained in a subsample of women at both the spine and femoral neck. Results : A total of 4023 postmenopausal women, aged 50–64 years, were studied: 73% reported a history of flushing, 45% sleep disturbance and 23% ‘other’ symptoms, at or around their menopause. The prevalence of vertebral deformity was 8.2%. Those with postmenopausal symptoms were slightly younger and more likely to have ever taken hormone replacement therapy (HRT) than those without symptoms. After adjusting for potential confounders (age, centre, body mass index, cigarette smoking and HRT) there was no association between deformity and any of the postmenopausal symptoms: flushing (odds ratio (OR) 1.0; 95% confidence intervals (CI) 0.8, 1.3), sleep disturbance (OR 1.0; 95% CI 0.8, 1.2), ‘other’ symptoms (OR 0.9; 95% CI 0.7, 1.3). Amongst women who had ever taken HRT, however, those with vertebral deformity were more likely to report a history of flushing (OR 2.1; 95% CI 0.9,4.8). Conclusion : A history of postmenopausal symptoms per se does not appear to be associated with increased susceptibility to vertebral osteoporosis. However, women with more severe symptoms (as suggested by their use of HRT) may be at increased risk.

This study documented bone loss at three different sites in the early postmenopausal period, and examined potential predictors. Forty-three women underwent repeated measurements of bone density at the lumbar spine, proximal femur and distal radius for up to 14 years. Individual rates of bone loss were calculated for the spine and hip; for radial trabecular bone, rates were calculated separately for two time periods, earlier and later after menopause. In the spine and radius, initially high rates of loss diminished with time after menopause. No positive correlations for bone loss were found between the three sites, suggesting that faster than average bone loss was specific to individual bones. High body mass index (BMI) was significantly protective against fast bone loss at the spine and radius; in the spine, each unit increase in BMI was associated with a approximately 5% reduction in the rate of bone loss. Of the other variables measured (maximum oxygen consumption, lean body mass, fat mass, mean psoas muscle area at the L3 level, hand grip strength as well as anthropometry) only bone densitometry was sufficiently predictive to help guidance on hormone replacement or other prophylactic therapy. The data suggest that the known relationship between excessive leanness and risk of osteoporosis and vertebral fracture after menopause might in part be due to fast post-menopausal bone loss. Because bulk of psoas muscle was associated with low spine loss rates, the data also support a role for applied muscular loading in local maintenance of bone density.

We have measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) of the spine and hip, spinal quantitative computed tomography (QCTspi), and peripheral radial quantitative computed tomography (pQCTrad) in 334 spine and 51 hip fracture patients. The standardized hip and spine BMD for each patient was calculated and compared with the combined reference ranges published previously, each densitometer having been cross- calibrated with the prototype European Spine Phantom (ESPp) or the European Forearm Phantom (EFP). Male and female fracture cases had similar BMD values after adjusting for body size, where appropriate. This suggests that the relationship between bone density (mass per unit volume) and fracture risk is similar between men and women. However, compared with age-matched controls, mean decreases in BMD ranged from 0.78 SD units (women with hip fracture, DXAspi) to 2.57 SD units (men with spine fractures, QCTspi). The proportion of spine and hip fracture patients falling below the cutoff for osteoporosis (T-score

The aetiology of rheumatoid arthritis (RA)-related pulmonary fibrosis (PF), one of the major extra-articular manifestations of RA (1), remains unknown and is likely to be multifactorial (2). Howeve...

Background Methotrexate (MTX) is the most commonly prescribed disease modifying anti-rheumatic drug in the treatment of rheumatoid arthritis (RA). Patients taking MTX are advised to restrict their alcohol consumption because of a theoretical hepatotoxic interaction between alcohol and MTX. However data are limited to support this advice. Objectives To quantify the association between alcohol consumption and abnormal serum liver function tests (LFTs) in patients with RA taking MTX, using routinely collected clinical data. Methods Patients with RA in the Clinical Practice Research Database (CPRD) starting MTX between 1987 and 2011 were studied. Patients were included if they had alcohol consumption details recorded in CPRD and ≥6 LFTs per year, indicating adequate monitoring. Patients were grouped by reported weekly alcohol consumption. Crude rates of abnormal LFTs (defined as alanine transaminase or aspartate aminotransferase level ≥3 times the upper limit of normal) per 1000 person-years follow up were calculated. Cox proportional hazards models described the association between alcohol consumed and development of abnormal LFTs whilst taking MTX univariately, then adjusting for age and gender. Patients were censored at time of first abnormal LFT, death or the end of follow up (31/12/2011). Results 8801 patients were included in the study, 6285 (71%) female, mean age (SD) was 58 (14) years. There were 241 abnormal LFTs in 38000 person-years follow up. There was no difference in rates of abnormal LFTs between drinkers and non-drinkers, adjusted hazard ratio (HR) (95% confidence interval (CI)) 1.12 (0.82–1.51). Crude rates of abnormal LFTs appeared to increase with increasing levels alcohol consumption (table 1); similarly when treated as a continuous variable, each increased unit of alcohol consumed was associated with a higher risk of abnormal LFTs, adjusted HR (95%CI) 1.01 (1.00–1.02). In the adjusted Cox model, moderate alcohol consumption (≤14 units per week) was not associated with a statistically significant risk of developing abnormal LFTs (table 1). There was a non-significant trend to higher HR with higher levels of alcohol consumption, however power was limited in the patients consuming >14 units per week. Conclusions In patients with RA taking MTX, increasing alcohol consumption is associated with an increased risk of developing abnormal LFTs. The clinical importance of this increased risk may be small when drinking ≤14 units per week. Disclosure of Interest None declared

Background There is concern that women with rheumatoid arthritis (RA) are at increased risk of high-grade cervical dysplasia (HGCD) detected via cervical smear. There is also controversy regarding the effect of chronic disease/disability on routine cancer screening attendance in this population. Objectives To (1) compare uptake of cervical screening for women with RA in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) with the general population and (2) compare frequency of HGCD between RA and the general population and between patients with RA ever versus never exposed to biologics. Methods The BSRBR-RA, a prospective cohort study, was linked to the NHS Cervical Screening Programme England (CSPE). Data from 2004–2014 was analysed in line with CSPE methods who publish coverage analysis annually; coverage is defined as the number of women who have been adequately screened at the defined age-dependent review period out of the total number of women eligible for screening in this period. Annual coverage was calculated for the eligible BSRBR-RA population and compared to national statistics. Within the BSRBR-RA, coverage was also compared between those patients with mild/moderate disability (mean Health Assessment Questionnaire (HAQ) scores Rates of HGCD (moderate dyskariosis or greater) and low grade cervical dysplasia (LGCD, borderline or mild dyskariosis) were compared to rates of negative smears using risk difference calculations between the BSRBR-RA and national statistics, and between the biologic naive (standard DMARD therapy) and biologic exposed cohorts within the BSRBR-RA. Results Of 13565 linked records, 12939 women had RA of which 12785 had cervical screening data, 2132 (17%) on nbDMARD therapy and 10653 (83%) with biologic exposure. Between 2004–2014 mean five-year coverage was higher in the BSRBR-RA population at 82.5% (95% CI 81.9, 83.1) compared to 79.0% (95% CI 78.5, 79.6) nationally. This mostly reflects significantly higher age appropriate coverage in the 25–49 year group for the BSRBR-RA population: 77.2% (95% CI 75.9, 78.6) compared to 71.4% (95% CI 70.2, 72.6) nationally. Coverage was higher among women with HAQ The risk of HGCD was lower in the BSRBR (0.9%) compared to the general population (1.3%) with a risk difference of -0.004 (95% CI -0.005, -0.002). The risk of LGCD was higher in the BSRBR (7.5%) compared to the general population (5.4%) with a risk difference of 0.021 (95% CI 0.017, 0.025). There was no significant risk difference for HGCD between the biologic and nbDMARD cohorts at 0.009 (95% CI -0.003, 0.021). Conclusions Women in the BSRBR-RA in England have higher rates of cervical screening attendance than the general population, although high HAQ scores had a negative effect on screening attendance. Those aged 25–49 years had markedly higher attendance; this may reflect familiarity with accessing healthcare. Cytology analysis suggests lower risk for HGCD in the RA group but higher risk for LGCD; this may reflect increased screening attendance. Women receiving biologic therapy were not at an increased risk of HGCD compared to those receiving standard DMARD therapy. Disclosure of Interest None declared

Background Early diffuse cutaneous systemic sclerosis (dcSSc) has high morbidity and mortality, and there is currently no cure. Objectives The main objective of ESOS (European Scleroderma Observational Study) was to compare the effectiveness of currently used immunosuppressant treatments. Methods ESOS was a prospective observational cohort study, capturing entry and outcome data in a standard way. Four recommended treatment protocols were decided by the steering committee: methotrexate (MTX), mycophenolate mofetil (MMF), cyclophosphamide, and “no immunosuppressant”. Patients were assessed at baseline, and then 3-monthly for 24 months or (for those entering the study subsequent to September 2013) at least 12 months. The primary outcome measure was the change in modified Rodnan skin score (mRSS – 17 sites) between 0 (baseline) and 12 months. Secondary endpoints largely reflected routine clinical practice and are not reported here. Effects of treatment on the skin score were assessed using linear regression with baseline treatments as predictors. Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights, while censoring weights adjust for bias due to patient attrition. Survival in each protocol was estimated using Kaplan-Meier curves and survival differences were tested based on the results of an IPT-weighted Cox regression model. Results Target recruitment was achieved, with 326 patients from 50 centres (median age 52.3 years, 72% female, median disease duration 11.1 months). Because this was not a randomized study, the number of patients starting on each treatment protocol differed: 65 MTX, 117 MMF, 87 cyclophosphamide, and 57 no immunosuppressant treatment. 273 patients (84%) completed 12 months follow-up and 179 (55%) 24 months follow-up. Median mRSS at baseline was 21.0 units. After 12 and 24 months, 153 (56%) and 139 (78%) of remaining patients had an improved skin score with respect to baseline. The mean change in mRSS after 12 and 24 months was -2.9 and -6.8 units. Predicted decreases in mRSS in each of the protocols are summarized in Figure 1. In both weighted and unadjusted models, the differences between the treatment groups are non-significant (p=0.27 and p=0.16). At 24 months, Kaplan-Meier predicted survival rates (adjusted for confounding) are 94% (MTX), 90% (MMF), 91% (cyclophosphamide) and 87% (no immunosuppressant). However, differences are non-significant (p=0.42). Conclusions 1. All groups showed improvement in MRSS which was not significantly different between groups although there was a trend in favour of methotrexate and MMF. 2. Survival was similar between groups although the no immunosuppressant group had lower survival (but it is important to stress that this was not a true “control” group). Disclosure of Interest None declared

Background Corticosteroid (CS) use has been identified as a key factor associated with damage in SLE but detailed analyses of patterns of use in large international cohorts have not previously been reported. Objectives To describe oral (PO) and parenteral CS use in a large international SLE cohort. Methods The SLICC Inception Cohort recruited patients within 15 months of developing ≥4 1997 American College of Rheumatology (ACR) criteria for SLE, between 2000 and 2011. Details of PO and parenteral steroid use were captured at enrolment and each annual assessment, including type, dose and course dates. All CS data was converted to prednisolone equivalents and analysed using Stata 13. Results 1848 patients have been recruited to the Cohort. Those with follow up data (1686) are included in this analysis, providing data on 10,572 annual follow-up (FU) intervals. The mean (SD) total FU is 6.72 (3.60) years; 1072 (63.5%) patients contributed ≥5 years FU; 343 (20.3%) contributed ≥10 years FU. The proportion of time spent on PO CS can be calculated for 10,098 (95.5%) FU intervals. For the majority of FU intervals (n=9103 (90.1%)), NONE (4494 (44.5%)) or ALL (4609 (45.6%)) of the time was spent on PO CS. In 995 (9.9%) FU intervals, only a proportion of the time was spent on PO CS. In those FU intervals where PO CS have been received (n=5604) the median (IQR) “average daily PO dose” was 6.5 (4.75–10) mg. The average daily CS dose decreased in later FU intervals: median (IQR) at FU 1=10 (5–15) mg and at FU 5=5.5 (4.8–10.0) mg. 558 (34.7%) patients have been on PO CS for ALL of their time in the study, 720 (44.8%) for some of it and 330 (20.5%) have never been on PO CS. 228 patients (13.5%) received parenteral CS prior to and/or at enrolment at a median (IQR) total dose of 1.5 (0.5–3.0) g. CS pulses were given during 429 (4.37%) FU intervals at a median (IQR) total dose of 679.5 (120–2500) mg. This compares to a median (IQR) cumulative total PO dose between FUs of 2565 (1575–4462) mg. PO CS use between FUs (using various definitions - see table 1) was higher in those FU intervals in which pulsed CS have also been given. Conclusions CS are widely prescribed in this international SLE cohort. 79.5% have been on CS at some point and 1 in 3 patients have taken CS throughout their entire disease duration. PO CS tend to be given at low daily doses for long periods of time but with a higher average daily dose earlier in the disease. Parenteral steroid use is associated with higher overall PO CS use, however PO CS contribute most to the total cumulative dose that patients receive. Current management of SLE still relies on CS use as a mainstay of therapy in a high proportion of patients. Acknowledgement The Systemic Lupus International Collaborating Clinics (SLICC) acknowledge funding support of UCB Pharma for this study. Disclosure of Interest None declared

Background Corticosteroids (CS) have been identified as a key factor associated with long term damage in systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) has been extensively validated and a previous analysis (Gladman et al J Rheumatol 2003;30:1955–9) suggested that SDI items can be grouped according to their likely association with CS. Objectives To generate international expert consensus opinion on which SDI items have an association with the use of CS. Methods We performed a Delphi exercise amongst SLICC members and associates. A survey requested expert opinions on how each SDI item was influenced by CS use on a Likert scale. The scale ranged from -3 to +3 where -3 = I believe that CS have a strong protective link with this item, 0 = I believe that CS have no effect on this item, +3 = I believe that CS have a strong causal link with this item. A second Delphi round presented each participant with their previous rating and the group median for that item, providing the opportunity for revision. A preliminary univariate analysis of CS exposure against damage was performed within the SLICC Inception Cohort to assess the appropriateness of these groupings and if any other items needed reclassifying. Results Of 43 members/associates, 36 respondents returned 26 complete forms (60.5%). All 26 completed the second round (100%) after which adequate consensus was reached. Four items (cataract, osteoporosis, avascular necrosis and diabetes mellitus) were assessed to be highly likely to be related to CS (median & mode =3, Table 1). Ten other items were “probably”/“possibly” CS related by expert opinion. The remaining items were felt not to be associated with CS. The univariate analysis supported these groupings and identified a significant association between CS exposure and the muscle atrophy/weakness item (e.g. OR (95% CI) 6.81 (1.91–24.27) if on steroids for all of intervening follow up period c.f. some or none of the period). It was agreed that muscle atrophy/weakness should be reclassified into the 9definite association9 group. Conclusions A consensus exercise based on expert opinion and initial analysis in an international inception cohort has generated a preliminary classification of the 42 SDI items according to their likely association with CS. This classification system requires further validation but will facilitate studies examining the impact of CS exposure on SLE populations. Acknowledgement The Systemic Lupus International Collaborating Clinics (SLICC) acknowledge funding support of UCB Pharma for this study. Disclosure of Interest None declared

Background The association between TNF inhibitors and vasculitis-like events, possibly secondary to induction of autoantibodies, has been well reported. However, the incidence, drug-specific differences, and associated factors have been poorly characterised. The aim of this study was to assess the drug-specific risk, and associated factors, of vasculitis-like events in patients with rheumatoid arthritis treated with TNF inhibitors and non-biologic disease modifying antirheumatic drugs (nbDMARDs). Methods This analysis included two cohorts from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) recruited from Oct 1, 2001, to May 31, 2015: patients starting first TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) and a comparison cohort receiving nbDMARDs. After identification of vasculitis-like events, additional information from hospital consultants was sought for verification. The risk of an event was compared between the two cohorts with Cox proportional hazard models, adjusted using propensity scores (inverse probability of treatment weighting). Findings There were 95 incident vasculitis-like events (14 in 3640 patients on nbDMARD, 81 in 12 745 patients starting first TNF inhibitors) with 20 365 and 52 428 patient-years of follow-up generating crude incidence rates of 7 per 10 000 and 16 per 10 000 person-years, respectively. After adjustment, the hazard ratio (HR) of vasculitis-like events in patients on TNF inhibitors versus nbDMARD was 1·3 (95% CI 0·4–4·0). Drug specific HRs were highest in patients on infliximab (HR 2·7, 95% CI 1·4–5·2) and etanercept (2·6, 1·4–4·8), but these associations were not significant after adjustment. Factors associated with vasculitis-like events included baseline disease activity (HR 1·4, 95% CI 1·2–1·7), rheumatoid factor positive status (1·8, 1·2–2·8), health assessment questionnaire score (1·7, 1·2–2·3), and sulfasalazine use (0·6, 0·3–0·9). Interpretation In one of the largest registers of patients receiving biological drugs, the absolute risk of vasculitis-like events was low, irrespective of whether patients received TNF inhibitors or nbDMARDs. There were no significant differences in risk between TNF inhibitors after adjustment. Higher baseline disease activity and seropositive status were associated with higher rates of vasculitis events, whereas baseline sulfasalazine use was associated with lower rates. To our knowledge, this is the first study to date to assess the risk of this outcome in a prospective, observational cohort. Funding Medical Research Council.

Propensity score calibration (PSC) can be used to adjust for unmeasured confounders using a cross-sectional validation study that lacks information on the disease outcome (Y), under a strong surrogacy assumption. Using directed acyclic graphs and path analysis, the authors developed a formula to predict the presence and magnitude of the bias of PSC in the simplest setting of a binary exposure (T) and 1 confounder (X) that are observed in the main study and 1 confounder (C) that is observed in the validation study only. PSC bias is predicted on the basis of parameters that can be estimated from the data and a single unidentifiable parameter, the relative risk (RR) associated with C (RR(CY)). The authors simulated 1,000 cohort studies each with a Poisson-distributed outcome Y, varying parameter values over a wide range. When using the true parameter for RR(CY), the formula predicts PSC bias almost perfectly in this simple setting (correlation with observed bias over 24 scenarios assessed: r = 0.998). The authors conclude that the bias from PSC observed in certain scenarios can be estimated from the imbalance in C between treated and untreated persons, after adjustment for X, in the validation study and assuming a range of plausible values for the unidentifiable RR(CY).

Introduction Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. Methods A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. Results The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). Conclusion A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.

Objective To compare the effectiveness of rituximab (RTX) or a second anti–tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients who had failed their first anti-TNF and switched to either RTX or a second anti-TNF, in routine clinical practice. Methods RA patients were registered with the British Society for Rheumatology Biologics Register. Response to treatment 6 months after switching was assessed using European League Against Rheumatism (EULAR) criteria and improvements in a Health Assessment Questionnaire (HAQ) score (0.22 unit or more). Regression analyses were used to compare EULAR response and improvement in HAQ score between the 2 groups, adjusting for propensity scores. Results In total, 1,328 patients were included in the analysis of EULAR response, and 937 patients were included in the analysis of HAQ scores. Six months after switching, 54.8% of patients who switched to RTX were EULAR responders compared to 47.3% of those who switched to a second anti-TNF. A total of 38.4% of RTX patients achieved a clinically important improvement in HAQ score compared to 29.6% in anti-TNF patients. After adjustment using propensity scores, patients who switched to RTX were significantly more likely to achieve EULAR response (odds ratio [OR] 1.31; 95% confidence interval [95% CI] 1.02, 1.69) compared to those who switched to an alternative anti-TNF. RTX patients were also significantly more likely to achieve improvements in HAQ score (OR 1.49; 95% CI 1.07, 2.08). Conclusion The results suggest that switching to RTX may be of more benefit than switching to an alternative anti-TNF therapy after failing the first anti-TNF therapy in RA patients.

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/m2). Morbid obesity (BMI ≥35 kg/m2) 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.

Objective.To assess the effectiveness of rituximab (RTX) in patients with rheumatoid arthritis (RA) in routine clinical practice, and to identify predictors of 6-month response to RTX in patients for whom at least 1 anti-tumor necrosis factor-α (anti-TNF) therapy has failed.Method.The analysis involved 646 patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR) who were starting RTX and were followed for at least 6 months. Change in the 28-joint Disease Activity Score (DAS28), European League Against Rheumatism (EULAR) response, and proportions of patients achieving disease remission were used to assess the clinical response 6 months after starting RTX. Regression analyses were used to identify factors associated with the response in the patients for whom anti-TNF therapy had not worked. The models included baseline demographics, disease characteristics, baseline Health Assessment Questionnaire (HAQ), and drug history including biologic history.Results.The mean DAS28 at baseline was 6.2 (95% CI 6.1, 6.3), which decreased significantly to 4.8 (95% CI 4.7, 4.9) at the 6-month followup. Seventeen percent of the patients were EULAR good responders and 43% were moderate responders. Eight percent of the patients achieved disease remission. Subjects with higher baseline DAS28 score and those with positive rheumatoid factor (RF) status were significantly associated with a decrease in their DAS28 score (improvement), while women and patients with higher baseline HAQ score were less likely to improve.Conclusion.RTX has proven to be effective in routine clinical practice. When anti-TNF therapy fails, response to RTX was influenced by baseline DAS28 score, RF status, baseline HAQ score, and sex.

Objective It has been found that women with rheumatoid arthritis (RA) have a poorer prognosis than men. However, the impact of age at symptom onset is unclear. We investigated the relationship between these factors and functional disability in patients with recent-onset inflammatory polyarthritis (IP). Methods A total of 3,666 patients (66% women) were registered with the Norfolk Arthritis Register between 1990 and 2008. Functional disability was assessed using the Health Assessment Questionnaire (HAQ), adjusted for age at HAQ completion. Linear random-effects models were used to examine HAQ score over time, by sex and age at symptom onset (early = age

Objectives To identify baseline disease-related predictors in patients with early inflammatory polyarthritis (IP) for starting subsequent biological therapy and to determine if patients who failed their first non-biological disease-modifying antirheumatic drug (DMARD) within 6 months were more likely to need biological therapy. Methods Patients with early IP recruited between 1990 and 1994 (cohort 1) and between 2000 and 2004 (cohort 2) in the Norfolk Arthritis Register were included in this study. The association between possible predictors with the start of biological therapy was assessed using Cox proportional hazards regression models. Results 32/407 (7.9%) patients in cohort 1 and 45/416 (10.8%) patients in cohort 2 received biological therapy during follow-up. In both cohorts, anti-citrullinated protein antibody (ACPA) positivity (cohort 1, HR 7.62, 95% CI 2.46 to 23.58; cohort 2, HR 4.68, 95% CI 2.23 to 9.78) was the strongest predictor for starting biological therapy. In cohort 2, younger patients (HR 0.97, 95% CI 0.95 to 0.99) and patients who failed their first non-biological DMARD within 6 months due to inefficacy were also more likely to receive biological therapy (HR 2.35, 95% CI 1.05 to 5.27). Conclusion Patients with early IP who are ACPA positive, are younger or who fail their first non-biological DMARD due to inefficacy within 6 months are more likely to need biological therapy.

The Standards, Audit and Guidelines Working Group (SAGWG) of the British Society for Rheumatology (BSR) have recently updated the guidelines on eligibility for anti-TNF drugs in RA [1] and have updated the anti-TNF safety and efficacy guidelines [2] for general use of the rheumatology community. The National Institute for Heath and Clinical Excellence (NICE) in the UK, which is the is an independent organization responsible for providing national guidance in the UK on promoting good health and preventing and treating ill health, has published a technology appraisal guidance [3] for use of rituximab in RA in 2007. Furthermore, a consensus statement from EULAR [4] was also published in 2007. Therefore, it was felt appropriate to undertake a review of the currently available data as new evidence was available. The group did not wish to duplicate the guidance in those documents, but wished to review the more recent evidence and supplement what is already known.

OBJECTIVE: Use of oral contraceptives (OCs) may prevent the development of rheumatoid arthritis but the influence of OC use on disease outcome is unresolved. The purpose of this study was to examine functional outcome and OC use in women with inflammatory polyarthritis (IP). METHODS: The Norfolk Arthritis Register (NOAR) is an inception cohort of patients with recent-onset IP. We studied patient-reported history of OC use in 663 women who were born after 1945 and who had not used OCs during followup. OC use during followup was additionally investigated in 265 women who were

Objective: To test the predictive ability of remission in terms of long-term disability in patients with recent-onset inflammatory polyarthritis (IP). Methods: Consecutive patients with early IP, recruited between 1990 and 1994 (first cohort) and 2000 and 2004 (second cohort), were included in this study. Remission was defined as the absence of clinically detectable joint inflammation on a 51-joint count. In additional analyses, less stringent definitions of remission were used based on the 40-and 28-joint counts. Remission was assessed at 1, 2, and 3 years after inclusion. A 5-year Health Assessment Questionnaire score ≥1 (moderate disability) was chosen as the primary outcome measure. Results: A total of 841 and 498 patients from the first and second cohorts, respectively, completed 5 years of followup. In the first cohort, patients with at least 1 episode of remission had lower odds of 5-year disability (odds ratio [OR] 0.26, 95% confidence interval [95% CI] 0.17-0.41). The number of times in remission correlated with the odds of disability, with a mean decrease in the probability of disability of ∼64% for each additional time point in remission (OR 0.38, 95% CI 0.28-0.52). The time until first remission was not associated with functional disability. Remission according to less stringent criteria showed a weaker protection against future disability. Similar results were found in the second cohort. Conclusion: Patients with IP achieving a state of sustained remission early are less likely to show long-term deterioration of function compared with patients who do not achieve remission. The most persistent remission under the most stringent definition of remission has the lowest probability of long-term disability. © 2011, American College of Rheumatology.