Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network.

OBJECTIVES: To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. METHODS: Demographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6-3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit. RESULTS: Of 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3-5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points). CONCLUSION: These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28.

The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.

The association of obesity with disease activity, functional ability and quality of life in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Study/Early Rheumatoid Arthritis Network UK prospective cohorts.

OBJECTIVES: To examine associations between BMI and disease activity, functional ability and quality of life in RA. METHODS: Data from two consecutive, similarly designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS) and the Early RA Network (ERAN). Recruitment figures/median follow-up for the ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years), respectively. Standard demographic and clinical variables were recorded at baseline and annually. Multilevel piecewise longitudinal models with a change point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as dependent variables. BMI was examined in separate models as both continuous and categorical variables (based on World Health Organization definitions) and up to 5 years from disease onset. RESULTS: BMI data from 2386 newly diagnosed RA patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI 0.21, 0.33). Baseline obesity was associated with a significant reduction in the odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2, HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at year 2, but not at year 5, and also associated with significantly higher HAQ and SF-36 PCS scores at years 2 and 5. CONCLUSION: Obesity prevalence is rising in early RA and associates with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low DAS28. The data argue strongly for obesity management to become central to treatment strategies in RA.

Can Rheumatologists Predict Eventual Need for Orthopaedic Intervention in Patients with Rheumatoid Arthritis? Results of a Systematic Review and Analysis of Two UK Inception Cohorts.

PURPOSE OF REVIEW: The structural damage caused by rheumatoid arthritis (RA) can often be mitigated by orthopaedic surgery in late disease. This study evaluates the value of predictive factors for orthopaedic intervention. METHODS: A systematic review of literature was undertaken to identify papers describing predictive factors for orthopaedic surgery in RA. Manuscripts were selected if they met inclusion criteria of cohort study design, diagnosis of RA, follow-up duration/disease duration ≥3 years, any orthopaedic surgical interventions recorded, and then summarised for predictive factors. A separate predictive analysis was performed on two consecutive UK Early RA cohorts, linked to national datasets. RECENT FINDINGS: The literature search identified 15 reports examining predictive factors for orthopaedic intervention, 4 inception, 5 prospective and 6 retrospective. Despite considerable variation, acute phase, x-ray scores, women and genotyping were the most commonly reported prognostic markers. The current predictive analysis included 1602 procedures performed in 711 patients (25-year cumulative incidence 26%). Earlier recruitment year, erosions and lower haemoglobin predicted both intermediate and major surgery (P<0.05). Studies report variations in type of and predictive power of clinical and laboratory parameters for different surgical interventions suggesting specific contributions from different pathological and/or patient-level factors. Our current analysis suggests that attention to non-inflammatory factors in addition to suppression of inflammation is needed to minimise the burden of orthopaedic surgery.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

OBJECTIVE: To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. METHODS: Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. RESULTS: A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). CONCLUSION: Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States.

OBJECTIVE: To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease-modifying antirheumatic drug treatment. METHODS: A total of 2,701 patients were recruited over 25 years to 2 UK-based RA inception cohorts: the Early Rheumatoid Arthritis Study (9 centers; 1986-2001) and the Early Rheumatoid Arthritis Network (23 centers; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed-effects models, including random effects for recruitment center. RESULTS: Age at onset increased from 53.2 to 57.7 years in 1990 and 2010, respectively (2.6 months/year; 95% confidence interval [95% CI] 1.2, 4.1). Sex ratio, the proportion living in deprived areas, and smoking status were unchanged (P > 0.05) and there were no changes in the proportion seropositive or erosive at baseline (P > 0.05). After controlling for treatment at the time of assessment, erythrocyte sedimentation rate decreased and hemoglobin increased over time (P > 0.05); however, the Health Assessment Questionnaire (HAQ), the Disease Activity Score (DAS), the DAS in 28 joints, and joint counts were unchanged (P > 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions, including hypertension. There was a significant increase in body mass index (0.15 units/year; 95% CI 0.11, 0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. CONCLUSION: Age at onset and comorbidity burden, especially obesity, have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast, there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity, or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of comorbidity on outcomes.

Have radiographic progression rates in early rheumatoid arthritis changed? A systematic review and meta-analysis of long-term cohorts.

OBJECTIVE: To evaluate, firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage. METHODS: A comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589). RESULTS: Meta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patients pre- and post-1990 (2.01% vs 2.03%; P > 0.01); however, the annual rate of progression was significantly reduced in the post-1990 cohorts (0.68% vs 1.50%; P < 0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and RF positivity remain consistently predictive of long-term radiographic joint damage. CONCLUSION: Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of RF/anti-CCP are strongly associated with increased radiographic progression.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds.

OBJECTIVES: To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. METHODS: Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6-3.2), low-moderate (LMDAS≥3.2-4.19), high-moderate (HMDAS 4.2-5.1) and high (HDAS>5.1). RESULTS: Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. CONCLUSIONS: There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.

The Effect of Disease Severity and Comorbidity on Length of Stay for Orthopedic Surgery in Rheumatoid Arthritis: Results from 2 UK Inception Cohorts, 1986-2012.

OBJECTIVE: To examine factors predicting length of stay (LoS) for orthopedic intervention in rheumatoid arthritis (RA). METHODS: LoS for orthopedic intervention was examined in 2 consecutive, multicenter inception cohorts: the Early RA Study (n = 1465, 9 centers) and the Early RA Network (n = 1236, 23 centers). Date, type of orthopedic procedure, and LoS were recorded and validated against national data, the UK National Joint Registry, and the UK Hospital Episode Statistics database. Clinical, laboratory, and radiographic measures and comorbidity recorded at baseline and annually were examined for their predictive power on LoS using regression analysis. RESULTS: A total of 770 of 2701 patients (28.5%) had 1602 orthopedic interventions: 40% major (mainly total hip/knee replacements), 24% intermediate (mainly hand/wrist and ankle/foot surgery), and 16% minor (mainly soft tissue surgery). Median (interquartile range) LoS was 8 (5-13), 3 (1-5), and 1 (0-2) days for major, intermediate, and minor interventions, respectively. Older age predicted longer LoS (p < 0.001) whereas a more recent operation year predicted shorter LoS (p < 0.001). Markers of active disease, namely low hemoglobin, high Health Assessment Questionnaire, and high Disease Activity Scores in the first year all predicted longer LoS for all types of surgery (p = 0.001, p < 0.001, p = 0.05, respectively). Presence of 1 or more major comorbidities predicted longer LoS (p < 0.001). CONCLUSION: Comorbidity and standard clinical and laboratory markers of disease activity affect the LoS for orthopedic surgery in RA, which has important clinical and economic implications, providing a target for improving patient outcomes.

Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but large-joint replacement rates remain unchanged: results from two UK inception cohorts.

OBJECTIVE: To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup. METHODS: The study examined orthopedic data from the UK Early RA Study (1986-1999, 9 centers; n = 1,465) and the UK Early RA Network (2002-2012, 23 centers; n = 1,236) with linkage to national data sets (Hospital Episode Statistics, National Joint Registry, and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardized and obtained yearly in both cohorts. The use of disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologic therapies reflected the contemporary conventional practices and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, and interventions were classified into major, intermediate, and minor categories. RESULTS: A total of 1,602 orthopedic surgical procedures were performed in 770 patients (29%) over a maximum of 25 years of followup. The 25-year cumulative incidence rate of major interventions was 21.7% (range 19.4-24.0%), and that of intermediate interventions was 21.5% (range 17.8-25.5%). There was a decline in the 10-year cumulative incidence of intermediate surgeries over time (P < 0.001), but not of major/minor surgery. This decline coincided with a gradual shift from sequential monotherapy to combination DMARD therapies and biologic agents in recent recruitment periods. CONCLUSION: Orthopedic surgery is an important and common outcome in RA. Only the rates of hand/foot surgery showed a consistent decline from 1986 to 2011. Possible explanations include differences in the pathophysiologic processes affecting the joints, variations in the responses to therapy between large-joint and small-joint destructive processes, and changes in service provision and thresholds for surgery over time.

Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality.

OBJECTIVE: This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. METHODS: Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. RESULTS: Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. CONCLUSION: The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.

Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumatoid arthritis study further replicates the TRAF1 association with radiological damage.

OBJECTIVE: The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques. METHODS: Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR). RESULTS: The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016). CONCLUSION: The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.

A study of baseline prevalence and cumulative incidence of comorbidity and extra-articular manifestations in RA and their impact on outcome.

OBJECTIVES: To study the prevalence at diagnosis and cumulative incidence of comorbidity in RA, associations with clinical features and impact on outcome. METHODS: Standard clinical, laboratory and radiological measures of RA, and details of comorbidity and extra-articular features were recorded at baseline and yearly in an inception cohort of 1460 patients with recently diagnosed RA from nine regions in the UK. The General Practice Research Database was used to compare the incidence of common comorbid conditions (International Classification for Disease-10 codes). RESULTS: Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage. CONCLUSION: Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.

Work disability rates in RA. Results from an inception cohort with 24 years follow-up.

OBJECTIVE: To explore rates of and reasons for work disability in an early RA cohort with median 10 years follow-up. METHODS: One thousand four hundred and sixty patients with early RA (<2 years symptom duration) and no prior DMARD therapy were recruited from nine rheumatology outpatient departments across the UK between 1986 and 1998. Standard clinical, laboratory and radiological assessments were recorded at 6-monthly and yearly intervals. Assessment of employment included details of type and hours of paid work. The main outcomes investigated were rates of and main reasons for work cessation, analysed by age of onset of RA (<45, 45-60 years) and year of recruitment to the study (before or after 1992). RESULTS: Maximum follow-up was 24 years, median 10 years. Of 647 patients in paid work at baseline, the majority were <60 years old (91%). The estimated probability of stopping work due to RA was highest in patients with older age of onset (45-60 years) who were recruited before 1992, but improved in those recruited from 1992 to 1998 (P < 0.01). There was no difference seen over the study recruitment years in younger age of onset patients. CONCLUSION: Work loss related to RA occurred much earlier than for other reasons, especially in the first 5 years of RA, but improved in the later recruitment period. Work disability is multifactorial, and the gradual changes in therapies used over time in this cohort may be one explanation for the secular differences seen.

Sustained clinical remission in rheumatoid arthritis: prevalence and prognostic factors in an inception cohort of patients treated with conventional DMARDS.

OBJECTIVE: Clinical remission is now a realistic goal in managing RA following the introduction of biologic agents. As there are limited data on sustained remission in conventionally treated RA, this study examines prevalence and predictive factors of sustained remission in a pre-biologic inception cohort of RA. METHODS: Patients with recent onset RA and before use of DMARDs were recruited from nine centres. Standard clinical and radiological assessments were recorded at baseline and yearly. Point remission was defined by DAS of <1.6, and sustained remission if DAS was <1.6 at all 3-, 4- and 5-year follow-ups. Sustained remission was compared with baseline features, with mortality and with radiological and functional progression in 704 patients. RESULTS: Point remission at 3, 4 and 5 years was 25, 26 and 22%, respectively. Eleven per cent (n = 78) had sustained remission. Male sex, short duration of symptoms and less tender joints at baseline were independent predictors of sustained remission. These patients had fewer DMARD therapies and less radiographic progression by 5 years. Mean HAQ decreased from 0.79 to 0.13 (P < 0.001) in sustained remission, compared with an increase from 0.92 to 1.1 (P < 0.001) in the non-remission group. CONCLUSION: Sustained clinical remission by 5 years with conventional DMARDs was 11%, half as likely as point remission. Prognostic factors were similar to comparable studies and simple to measure. Patients in sustained clinical remission showed less structural damage and better functional outcomes.

Biologic agents for rheumatoid arthritis--negotiating the NICE technology appraisals.

In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance [technology appraisals (TAs) 130, 186, 195, 198 and 225] on the use of biologic drugs for the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of ≥5.1. Alternative biologic agents are denied to those with contraindications to anti-TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist.

Use of conservative and surgical foot care in an inception cohort of patients with rheumatoid arthritis.

OBJECTIVES: To describe conservative and surgical foot care in patients with RA in England and explore factors that predict the type of foot care received. METHODS: Use of podiatry and type of foot surgery were outcomes recorded in an inception cohort involving nine rheumatology centres that recruited patients with RA between 1986 and 1998 across England. Associations between patient-specific factors and service use were identified using univariate logistic regression analyses. The independence of these associations was then verified through multiple binary logistic regression modelling. RESULTS: Data were collected on 1237 patients with RA [66.9% females, mean (s.d.) age at disease onset = 54.36 (14.18) years, median DAS = 4.09 (1st quartile = 3.04, 3rd quartile = 5.26), median HAQ = 1 (0.50, 1.63)]. Interventions involving the feet in the cohort were low with only 364 (30%) out of 1218 receiving podiatry and 47 (4%) out of 1237 patients having surgery. At baseline, female gender, increasing age at onset, being RF positive and higher DAS scores were each independently associated with increased odds of seeing a podiatrist. Gender, age of onset and baseline DAS were independently associated with the odds of having foot surgery. CONCLUSIONS: Despite the known high prevalence of foot pathologies in RA, only one-third of this cohort accessed podiatry. While older females were more likely to access podiatry care and younger patients surgery, the majority of the RA population did not access any foot care.

An evaluation of the strengths and weaknesses of a register of newly diagnosed rheumatoid arthritis, 1986-2010.

OBJECTIVES: To evaluate the strengths and weaknesses of a register of management and outcomes of recently diagnosed RA, and allow comparisons between rheumatology centres on good clinical practice and guidelines. METHODS: A register of newly diagnosed RA was initiated in 1986 in nine different regions of England, later expanded to UK-wide membership in 2002. Standardized data collection includes disease activity, function, radiological damage, therapy, hospitalizations, major comorbidity and mortality. A centralized database generates individual reports and comparative data for each centre yearly. Aims have been compared with actual achievements and any changes over 25 years. RESULTS: Thirty rheumatology centres have recruited 2866 patients. Study outputs have included peer-reviewed scientific publications and contributions to the recent National Audit Office report on RA. Referral times into secondary care have changed little over 25 years, but time to initiation of drug therapies has decreased. Delays between publication of clinical trial evidence and management guidelines and their implementation in normal clinical practice are illustrated by relatively infrequent use of combination therapies at diagnosis. Consecutive case recruitment, centre participation and follow-up were reportedly compromised by local funding issues. Centre participants report a benefit from feedback of actual clinical practice compared with recommended standards of care. CONCLUSIONS: Most of the original objectives have been achieved. Cohort studies based predominantly in District General Hospitals provide unique insights into the natural history and impact of RA, its management, the translation of research findings into clinical practice and provide participating centres with important clinical governance and professional development opportunities.