Methotrexate use and alcohol.

A literature review was performed to look at the interactions between alcohol and methotrexate in non-malignant disease. The evidence from research into psoriasis and inflammatory arthritis, and an overview of international and national guidelines, was amalgamated into some consensus recommendations.

Anti-TNF-alpha agents are less effective for the treatment of rheumatoid arthritis in current smokers.

OBJECTIVES: To assess if smoking status at the time of commencing an anti-TNF-alpha agent for rheumatoid arthritis (RA) reduces the likelihood of achieving at least a moderate response on the European League Against Rheumatism (EULAR) response criteria at 3-month assessment. METHODS: All patients with RA treated with their first anti-TNF-alpha agent at the Department of Rheumatology, Derby Hospital NHS Trust between April 2001 and October 2008 were included in this retrospective case control study. Information about age, gender, disease duration, body mass index, smoking status (current smoker, ex-smoker, and nonsmoker), comorbidities, oral prednisolone use, and 28 joint 4 variables disease activity score (DAS28) at the time of commencing an anti-TNF-alpha agent was recorded. Details of rheumatoid factor (RF) and past and present disease modifying antirheumatic drugs were recorded. A case control study was carried out to examine possible baseline predictors of treatment effects at the 3-month assessment. RESULTS: Results were available for 395 patients at 3-month assessment. According to the EULAR response criteria 42 patients failed to show at least a moderate response. After adjusting for confounders using multivariate analysis, current smoking at the time of commencing an anti-TNF-alpha agent reduced the chance of achieving at least a moderate response on the EULAR response criteria when compared with nonsmokers (aOR [95% CI] 0.20 [0.05-0.83], P = 0.03). CONCLUSIONS: RA patients who smoke are less likely to respond to an anti-TNF-alpha agent.

Analysis of rewarming curves in Raynaud's phenomenon of various aetiologies.

This study investigated whether a modified Cold Provocation Test could distinguish between 86 normal subjects and 31 patients with Raynaud's phenomenon or 59 with hand arm vibration syndrome (HAVS). Of the HAVS subjects, 56 were seen for medical reports as they were involved in litigation. Their assessments were done in a different location but the same protocol was used. A standardised cold stress was used to reduce the finger temperature to 15 degrees C or less without inducing reflex hyperaemia. This test had acceptable repeatability for subjects without HAVS with an intra-class correlation of 0.7. Baseline temperature, temperature rise in the first 30 seconds and the time taken to rewarm by 5 degrees C were measured. Patients with Raynaud's phenomenon and HAVS had cooler hands than controls. HAVS patients rewarmed most in the first 30 seconds. Patients with Raynaud's phenomenon take longer to rewarm by 5 degrees C than controls or those with HAVS (P<0.001). A baseline difference of >7.5 degrees C between the temperature of the digit and that of the room is unlikely to occur in patients with Raynaud's phenomenon or HAVS. A temperature gain of > or =2.2 degrees C in the first 30 seconds on rewarming combined with a low baseline temperature strongly suggests HAVS. This modified cold provocation test may differentiate between patients with Raynaud's phenomenon, HAVS and controls but this observation requires independent verification in subjects not involved in litigation and tested in the same facility.

The importance of the baseline Disease Activity Score 28 in determining responders and non-responders to anti-TNF in UK clinical practice.

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: a clinical perspective.

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.

An update on UK rheumatology consultant workforce provision: the BSR/ARC Workforce Register 2005-07: assessing the impact of recent changes in NHS provision.

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.

Discrepancies between the EULAR response criteria and the NICE guidelines for continuation of anti-TNF therapy in RA: a cause for concern?

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.

Is pre-assessment for anti-TNF therapy in RA necessary in the UK? Analysis of DAS28 in six centres.

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.

Characteristics and treatment responses of patients satisfying the BSR guidelines for anti-TNF in ankylosing spondylitis.

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.

Ages of onset suggestive of genetic anticipation in rheumatoid arthritis multicase sibships can be explained by observational bias.

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.

The impact of anti-tumour necrosis factor therapy for rheumatoid arthritis on the use of other drugs and hospital resources in a pragmatic setting.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has been an important development for the treatment of rheumatoid arthritis (RA) but the impact of its delivery on hospital resources in still emerging. AIMS: We audited the effect of starting anti-TNF on the use of other anti-rheumatic therapies and hospital resources in a routine secondary care setting. METHODS: A retrospective study of resource use before and after anti-TNF was conducted. Hospital records of 54 RA patients were studied and data taken from the time of commencing anti-TNF to 1 October 2004 and an equal time period prior to commencing anti-TNF. Identical data were collected for 54 controls not on anti-TNF. Relevant figures were extrapolated to per annum rates. Results were analysed using two-factor ANOVAs comparing the pre- versus post-anti-TNF period. Cases on intravenous (IV) versus subcutaneous (SC) anti-TNF were also compared in separate ANOVAs. RESULTS: Mean duration of anti-TNF therapy was 17.04 months (range 3.60-42.36). Mean pre- and 3-months post-anti-TNF Disease Activity Scores (DAS28) were 6.93 and 3.88, respectively. Cases were more likely than controls to be on oral prednisolone pre- and post-anti-TNF. Methylprednisolone requirement, number of disease-modifying anti-rheumatic drugs (DMARDs), telephone helpline contacts and duration as an inpatient reduced significantly post-anti-TNF. Day case admissions increased but outpatient appointments decreased only in cases on IV anti-TNF. CONCLUSIONS: In a pragmatic setting, anti-TNF therapy led to reduced need for steroid injections and other DMARDs, as well as reductions in use of several hospital resources. Wider replication of these findings will be important for planning delivery.