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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rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event.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.

Objectives: Anti-TNF therapy has improved outcomes for patients with highly active RA. Less is known about its effectiveness in patients with lower disease activity. The aim of this analysis is to compare the response to anti-TNF therapy between RA patients with high (DAS28 > 5.1) and moderate (DAS28 > 3.2-5.1) disease activity., Methods: A total of 4687 anti-TNF and 344 DMARD patients with high disease activity despite treatment with two standard DMARDs (including MTX) and 224 anti-TNF- and 300 DMARD-treated patients with moderate disease activity were selected from the British Society For Rheumatology Biologics Register. Mean change in HAQ over the first 12 months of enrolment was compared first between anti-TNF-treated and untreated patients in each DAS28 group, and then between anti-TNF-treated patients in the moderate and high DAS28 groups, using doubly robust estimates, adjusting for age, gender, disease duration, baseline HAQ and DAS28 score, number of previous DMARDs and steroid use., Results: Compared with anti-TNF-untreated patients within each DAS group, treated patients were younger, had higher DAS28 and HAQ and had failed a higher number of previous DMARDs. The mean adjusted change in HAQ over 12 months was similar in anti-TNF-treated patients with moderate and high disease activity at baseline: moderate -0.26 (95% CI -0.35, -0.16), high -0.28 (95% CI -0.34, -0.23) and mean difference -0.03 (95% CI -0.14, 0.08)., Conclusions: Improvement in HAQ score 12 months after start of anti-TNF therapy was not dependent on baseline DAS28 scores, suggesting that substantial benefits may also be gained by treating those with moderately active disease despite standard DMARD therapy.

Objectives: The NICE re-appraisal of anti-TNF requires demonstration of ongoing response, making the baseline 28-joint Disease Activity Score (DAS28) crucially important. A retrospective analysis of all RA patients on their first anti-TNF determined predictive factors for those classified as non-responders at 6 months according to current NICE guidelines., Methods: The patients were divided into responders (DAS28 dropped by >1.2) and non-responders. These groups were compared for demographics, DAS28 at the two pre-assessments 1 month apart and at baseline. Exposure to intramuscular, oral and IA steroids in the 3 months period before the baseline DAS28 was recorded., Results: At 6-month assessment in 256 patients, 82.8% were responders with no demographic differences between them and non-responders. Although the first pre-assessment score was not significantly different (6.8 vs 6.6), the second pre-assessment score (7.1 vs 6.7) and the baseline DAS (7.2 vs 6.3) were lower in the non-responders (P < 0.04 and P < 0.001, respectively). Comparing the differences in DAS28 from the first pre-assessment to baseline, the responders had increased by 0.4, and the non-responders had decreased by 0.4, (P < 0.001). If the first pre-assessment score had been taken as the baseline DAS28, then 9.4% of responders would be re-classified as non-responders, and 31.8% of non-responders would be re-classified as responders. The proportion of patients who had steroid treatment within the 3 months period before the baseline DAS28 did not differ significantly between the responders and non-responders (34% vs 41%, P = 0.38)., Conclusion: Baseline DAS28 is critical in classifying responders at the 6-month assessment.

Rheumatoid cachexia is under-recognized in clinical practice. The loss of lean body tissue, which characterizes cachexia, is often compensated for by gain in body fat-so called 'cachectic obesity'-so that 85% or more RA patients have a normal BMI. Severe cachexia with loss of weight leads to increased morbidity and premature mortality but loss of muscle bulk with a normal BMI also associates with poor clinical outcomes. Increasing BMI, even into the obese range, is associated with less joint damage and reduced mortality. Measurement of body composition using DXA and other techniques is feasible but the results must be interpreted with care. Newer techniques such as whole-body MRI will help define with more confidence the mass and distribution of fat and muscle and help elucidate the relationships between body composition and outcomes. Cachexia shows little response to diet alone but progressive resistance training and anti-TNF therapies show promise in tackling this potentially disabling extra-articular feature of RA.

Objectives: To describe changes in the provision of rheumatology services, monitor the pattern of inequalities in UK rheumatology service provision since 2005, and to summarize the 3-yr impact of the new National Health Service (NHS) consultant contract and the Musculoskeletal Services Framework in England and Wales., Methods: Questionnaires about timetable and working conditions were sent to all consultants on the BSR/ARC UK Workforce Register in January 2007, along with the personal and job-related details currently held about them on the register to update. The questionnaire included a visual analogue scale asking 'how concerned are you that your current post might be under threat' ranging from 0 'Not at all' to 100 'Extremely'., Results: The response rate of the 2005 and 2007 surveys were 89 and 87%, respectively. Levels of optimal provision now exceed 70% in England and Wales, and 50% in Scotland and Northern Ireland. Levels of provision remain substantially higher in London than anywhere else. The median level of perceived job threat in the UK was 31 (interquartile range 11-61). Consultants in areas where provision is highest and a higher proportion of services are run in conjunction with Clinical Assessment and Treatment (CAT) centres report higher perceived job threat., Conclusions: Provision of rheumatology services has continued to expand over the past decade; however, inequalities persist at national and sub-national level. There is evidence of improvement in regions with the lowest provision, but there are indications of increased perceived job threat in areas with traditionally higher provision and where CAT centres have been introduced.

Objectives: A discrepancy exists between the National Institute for Health and Clinical Excellence (NICE) guidelines for continuation of TNF therapy in RA and EULAR response criteria. We performed a retrospective study of patients starting anti-TNF therapy to establish how many NICE non-responders would have met EULAR response criteria, and whether this may increase., Method: We calculated the percentage of NICE non-responders who would have met EULAR moderate response criteria. We then compared the mean decrease in disease activity score (DAS28) for patients with low and high baseline scores. We analysed trends for treating RA in Derby with anti-TNF to address whether we were treating less active disease over time., Results: At 3 months (n = 271 patients), 7.7% of NICE non-responders would have met EULAR moderate response criteria. At 6 months (n = 240 patients) this was 23.7%. Patients starting with a higher DAS28 had a significantly greater absolute drop in score. The mean decrease between the 1st and 3rd tertiles of patients divided by baseline DAS28 was significant at 3 and 6 months (P < 0.001). Derby rheumatologists were treating less active RA over time. Comparing the mean DAS28 baseline between the 1st and 3rd tertiles of patients divided by anti-TNF commencement date was significant (P < 0.001)., Conclusions: A significant minority of NICE non-responders would fall within the moderate EULAR response criteria. This is likely to increase in future due to the increasing tendency to initiate anti-TNF in patients with less active disease. Consequently, NICE guidelines should be brought in line with EULAR response criteria.

Objectives: National Institute for Health and Clinical Excellence (NICE) guidelines for anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA) state that two pre-assessments of Disease Activity Score (DAS28) should be performed a month apart. We performed a retrospective audit of data from six centres to determine the stability of DAS28 between assessments, and the proportion of patients still satisfying eligibility criteria at baseline., Methods: All RA patients assessed for anti-TNF from six centres had their pre-assessment DAS28 (DAS-1) compared with their baseline DAS28 (DAS0) using paired t-tests, and a similar analysis for the components of the DAS28. Patients who were no longer eligible for anti-TNF at DAS0 were noted., Results: Six hundred and seventy-nine RA patients showed no significant change in the DAS28, with a mean DAS-1 of 6.74 and DAS0 of 6.73. (P = 0.86). Of the patients, 97.2% fulfilled the UK eligibility criteria at DAS0. Comparison of the individual components of the DAS28 between the two pre-assessment dates showed that there was no significant difference between either the numbers of swollen joints or the erythrocyte sedimentation rate (ESR), but there was a significant increase in the numbers of tender joints of 1.41 (P < 0.001) and in the visual analogue scale (VAS) of 4.22 (P < 0.001)., Discussion: The overwhelming majority of patients who fulfil eligibility criteria for anti-TNF drugs 1 month prior to baseline also fulfil the criteria at baseline. There is no significant change in the DAS28 over the month waiting to go onto anti-TNF therapy. A single assessment of the DAS28 would suffice to enable patients to go on to anti-TNF treatment.

Objective: We present the results of the response to anti-tumour necrosis factor (anti-TNF) of 30 ankylosing spondylitis (AS) patients where we have complied with the BSR guidelines., Method: All patients had pre-assessments of Bath AS Disease Activity Index (BASDAIs) at two points a month apart prior to commencing anti-TNF. They then had 2 week and 2 month assessments followed by 3 monthly thereafter. BASDAI, visual analogue scales, blood count and erythrocyte sedimentation rate (ESR) were performed on each occasion., Results: All patients had stable active disease at the pre-assessments with a mean BASDAI of 6.8. Twenty-nine patients showed a rapid and dramatic response with a mean BASDAI at 2 months assessment of 3.2 (P < 0.001). This was maintained for up to 20 months of follow up. Haemoglobin rose significantly (mean of 13.0 g/dl to 13.8) and the ESR dropped from 49 mm/h to 23 (both P < 0.001). Fifteen patients (51.7%) were able to stop their non-steroidal anti-inflammatory drugs (NSAIDs) and a further eight reduced them., Conclusion: Patients who fulfil the BSR guidelines for anti-TNF in AS have sustained active inflammatory disease prior to going onto etanercept or infliximab. Despite this, they show rapid, dramatic sustained responses to treatment, and over half are able to stop their NSAIDs. Any health economic analyses of anti-TNF in UK clinical practice need to take these observations into account.

Objectives: Previous work has suggested that features of genetic anticipation might be present in familial rheumatoid arthritis (RA), but bias is difficult to exclude when looking at disease in two consecutive generations. We used data from the North American Rheumatoid Arthritis Consortium (NARAC) and the Arthritis Research Campaign National repository for RA multicase pedigrees to determine whether differences in age of onset within multicase sibships were supportive of genetic anticipation., Method: RA sibling pairs were identified from both data sets. The period of observation was defined as the time between the first sibling developing RA and the time that the sibship was ascertained for the study. A paired t-test for the difference in ages of RA onset within the pairs was calculated. Ages of conception of the parent were correlated with the age of RA onset., Results: Information was available for 743 sibships in the NARAC data set and 396 sibships in the Arthritis Research Campaign (ARC) data set. In both data sets, the older siblings had an older age of onset than their younger siblings (39.3 vs 36.9 in the NARAC, and 43.8 vs 40.1 in the ARC data set, both P < 0.001). The two data sets were then stratified into tertiles by a period of observation. In both data sets, there was a progressive decline in the sibling age of onset differences. For the first tertile (shortest observation period), the older sibling had a significantly older age of onset than the younger. This difference decreased in the second tertile, and was not significant in the third tertile (longest observation period). There was no significant correlation between the age of RA onset and the maternal or paternal ages of conception in either data set., Conclusion: Features compatible with genetic anticipation in RA multicase sibships are subject to observational bias. This does not support a role for genetic anticipation in familial RA.

Background: To compare the core hand and knee examination skills gained by undergraduates taught either by trained patient educators (PEs) or by doctors., Methods: A total of 50 final year medical students were randomized to receive training from PEs or doctors. Group A were taught hand examination by a PE with rheumatoid arthritis, and knee examination by a PE with osteoarthritis. Group B was taught hand and knee examination by a consultant rheumatologist plus an untrained patient with appropriate signs. All students were taught an established core skills set in small group workshops. Students then undertook two validated objective structured clinical examination (OSCE) stations with two blinded assessors. Pre- and post-teaching questionnaires established the students' self-reported levels of skills (SRS) and a student evaluation of teaching (SET). The study was analysed as an equivalence trial. A mean difference in OSCE scores of 10% was assumed to be of educational significance., Results: Although the SET scores of both groups were high, the doctor-led group received higher scores. Aside from this, the two student groups did not differ significantly. There were no significant differences in mean hand OSCE (mean difference = 0.88, P = 0.28, 95% CI = -0.73 to 2.49) or knee OSCE (mean difference = 0.28, P = 0.7, 95% CI = -1.19 to 1.75) scores. Both the upper and lower confidence intervals for each mean difference fell within the 10% range (-2.8 to 2.8 for the hand, and -2.5 to 2.5 for the knee) and equivalence was assumed., Conclusions: Adequately trained PEs can deliver clearly structured undergraduate skills, teaching with equivalent learning outcomes to those of rheumatology consultants. PEs are a valuable development to augment musculoskeletal education in the face of expanding student numbers.

Objective: To determine whether final year medical students' perceptions of teaching workshops delivered by a consultant rheumatologist are similar those of the same workshops delivered by an experienced nurse clinical educator (NCE)., Methods: The design was a semi-randomized post-test intervention study. The consultant and NCE alternated in presenting eight teaching workshops to four groups of six final year medical students. After each of the workshops, students evaluated the feedback by self-completed questionnaires., Results: Seventy-three questionnaires were available from the consultant workshops and 65 from the NCE ones. There was no difference in the overall scores for the consultant and the NCE. The consultant scored significantly higher on two individual questions, but these differences were lost when we adjusted for multiple testing., Conclusion: We were unable to demonstrate a major difference between the feedback received from medical students in workshops delivered by an enthusiastic consultant and an experienced NCE.