Rheumatoid Arthritis: Scott DG

Deighton CM, George E, Kiely PD, Ledingham J, Luqmani RA, Scott DG. · No affiliation provided · Rheumatology (Oxford). · Pubmed #16527881 links to  free full text

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Griffiths I, Silman A, Symmons D, Scott DG. · No affiliation provided · Rheumatology (Oxford). · Pubmed #15328420 links to  free full text

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O'Gradaigh D, Scott DG. · Department of Rheumatology, Addenbrook Hospital, Cambridge, UK. · Clin Exp Rheumatol. · Pubmed #10589352 No free full text.

Abstract: Rheumatoid arthritis continues to be a cause of significant morbidity and disability. Increased understanding of the immunopathogenesis of the disease, of its progression over time, and of patient characteristics which correlate with outcome, have allowed more appropriate therapy. However, currently available disease-modifying therapy fails to adequately control disease in many patients, and many combinations of these drugs have therefore been described. In this review, we critically evaluate the existing literature, identifying combinations for which reasonable evidence of efficacy exists, and highlighting important issues in interpreting such evidence as well as issues of drug monitoring in such patients.

Jois RN, Masding A, Somerville M, Gaffney K, Scott DG. · Department of Rheumatology, East block, Level-2, Norfolk and Norwich University Hospital, Colney lane, Norwich NR4 7UY, UK. · Rheumatology (Oxford). · Pubmed #17384180 links to  free full text

Abstract: OBJECTIVES: Rituximab has recently been shown to be effective in suppressing disease activity in patients with rheumatoid arthritis (RA) who fail anti-TNF therapy. We present our experience of treating patients with long-standing, multi-DMARD and anti-TNF resistant RA with rituximab in 'real-life' setting. METHODS: Patients with RA resistant to more than two anti-TNF drugs and with persistent disease activity (DAS28 > 5.1) were considered for treatment with rituximab (two infusions 1000 mg each, a fortnight apart). DAS28 and HAQ scores were performed at baseline, 3 and 6 months post-treatment. Response to rituximab was defined as per the EULAR response criteria. Re-treatment with a second cycle of rituximab was offered if they had responded to the earlier one but flared. RESULTS: Twenty patients received rituximab. Median disease duration was 16 yrs (range 5-39) and 90% were rheumatoid factor positive. Median number of biologics received pre-treatment was two (range 2-4). Rituximab treatment led to a significant reduction in DAS28 score (P < 0.0001) at 3 months and various other disease parameters. The benefit was sustained at 6 months. Moderate-to-good EULAR response was seen in 85% of patients at 3 months and 60% at 6 months. No significant side effects were observed. 50% of the patients flared and received re-treatment. Interval to re-treatment varied from 6 to 18 months. The majority of the RA patients responded to re-treatment with rituximab and no major side effects were observed. CONCLUSION: Rituximab was effective in controlling disease activity in anti-TNF therapy resistant RA patients in 'real-life' setting. Rituximab was safe with no major side effects. Re-treatment with rituximab was safe and efficacy was maintained.

Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DG, Patel J, Sopwith M, Isenberg DA. · Academic Department of Rheumatology, GKT School of Medicine, King's College London, King's College Hospital, London, UK. · Rheumatology (Oxford). · Pubmed #12364632 links to  free full text

Abstract: OBJECTIVE: Biological products that neutralize tumour necrosis factor alpha (TNF-alpha) are beneficial in rheumatoid arthritis (RA). We studied the effects of CDP870, a novel anti-TNF-alpha antibody fragment modified to obtain a prolonged plasma half-life ( approximately 14 days). METHODS: Thirty-six patients were randomized in a double-blind, ascending-dose group study to a single intravenous infusion of placebo (n = 12) or 1, 5 or 20 mg/kg CDP870 (each n = 8). The patients were predominantly female (30/36), had a mean age of 56 yr and a mean duration of RA of 13 years. They had received a mean of five DMARDs or experimental therapies (with 1 month washout before the study started) and had active disease. Continuation of NSAIDs and up to 7.5 mg prednisolone daily was allowed. Following the blinded dosing period, 32 patients received a single open-label infusion of either 5 or 20 mg/kg CDP870. RESULTS: In the blinded dosing period, 6/12 placebo patients withdrew from the study (for deteriorating RA < or =4 weeks after dosing). Two of 24 CDP870-treated patients withdrew, both in the 1 mg/kg group (for deteriorating RA or lost to follow up >4 weeks after dosing). The proportion of patients with ACR20 improvement for the per-protocol population with the last observation carried forward was 16.7, 50, 87.5 and 62.5% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.012, primary analysis) at 4 weeks and 16.7, 25, 75 and 75% (P = 0.032) at 8 weeks. The proportion of patients with ACR50 improvement for the per-protocol population with the last observation carried forward was 0, 12.5, 12.5 and 50% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.079) at 4 weeks and 0, 12.5, 12.5 and 50% (P = 0.079) at 8 weeks. Following the open-label dose of CDP870, similar beneficial effects were achieved. CONCLUSION: CDP870 is effective, was very well tolerated in this small study, and has an extended duration of action following one or more intravenous doses.

Oliver S, Bosworth A, Airoldi M, Bunyan H, Callum A, Dixon J, Home D, Lax I, O'Brien A, Redmond A, Ryan S, Scott DG, Steuer A, Tanner L. · Litchdon Medical Centre, Devon, UK. · Musculoskeletal Care. · Pubmed #18785194 No free full text.

Abstract: OBJECTIVE: Consumers of healthcare can reveal important insights into the personal challenges they experience when negotiating their health needs. The National Rheumatoid Arthritis Society (NRAS) wanted to explore the experiences of those with rheumatoid arthritis (RA) in order to understand the impact on the individual and on healthcare resources and benchmark care against published standards and guidelines. METHODS: A project was designed to explore the experiences of individuals with sero-positive RA who had been diagnosed for three years or less. Qualitative semi-structured interviews were used and combined with process mapping to explore the experiences of a purposeful sample of individuals with RA. The information generated was mapped and variances explored. Ethical approval was not required as the data were collected outside the National Health Service. RESULTS: Twenty-two participants' stories were mapped. Fifty per cent of participants sought a medical opinion within three weeks of symptom onset and the majority received a disease-modifying anti-rheumatic drug within six months from first presenting symptoms. Work-related issues were highlighted by 13 participants, and seven of these experienced job losses directly attributed to their diagnosis. CONCLUSIONS: This unique mapping approach used qualitative research and process mapping to compare patient experiences against recognized standards and guidelines. These twenty-two stories reveal important insights into the challenges experienced in negotiating these healthcare journeys and the impact upon the individual as a result of variances in standards of care received. The participants in this study were chiefly self-motivated, informed and articulate, and did not reflect the broad ethnic, social or cultural diversity in the UK. Limitations must also be considered in relation to perceptions and recall of participants over a three-year period, as these may have altered over time and illness experience.

Teir J, Koduri G, Meadows A, Griffin J, Kelsey C, Kola A, Persey M, Sinclair H, Yuksel F, Moshtaghi P, Ramabhadram B, Poole K, Pradeep J, Lane S, Pountain G, Scott DG, Sheehan NJ, Stodell M, Young A, Hall FC. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18573801 No free full text.

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Morgan C, Lunt M, Bunn D, Scott DG, Symmons DP. · ARC Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. · Rheumatology (Oxford). · Pubmed #18032539 No free full text.

Abstract: OBJECTIVES: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. METHODS: Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. RESULTS: Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. CONCLUSIONS: Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.

Ostör AJ, Chilvers ER, Somerville MF, Lim AY, Lane SE, Crisp AJ, Scott DG. · Rheumatology Department, Addenbrooke's Hospital, Cambridge, UK. · J Rheumatol. · Pubmed #16511933 No free full text.

Abstract: We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.

Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. · University of Manchester, UK. · Arthritis Rheum. · Pubmed #16052597 links to  free full text

Abstract: OBJECTIVE: To test the hypothesis that the C-reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP). METHODS: Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD. RESULTS: The median followup was 10.1 years (interquartile range 9.3-10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (> or=5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2-13.4) for men, and HR 4.22 (95% CI 1.4-12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7-32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4-7.6]). CONCLUSION: The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new-onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.

Ramjeet J, Koutantji M, Barrett EM, Scott DG. · School of Nursing and Midwifery Research Unit, Yorkon Building, University of East Anglia, Norwich, Norfolk, UK. · Rheumatology (Oxford). · Pubmed #15941729 links to  free full text

Abstract: OBJECTIVES: To examine the role of gender, age and coping in psychological adjustment of patients with early inflammatory polyarthritis (IP). METHODS: One hundred and twelve patients with IP of up to 18 months' duration from the Norfolk Arthritis Register completed questionnaires measuring coping, anxiety, disability and pain. RESULTS: Thirty-six per cent of the patients were at risk of depressive symptoms. Women had significantly higher levels of depression and anxiety than men. Regression analyses showed that pain and (low) illness acceptance predicted levels of depression. Younger age, wishful thinking and covering up predicted anxiety levels. CONCLUSIONS: The study found higher levels of depression and anxiety for women than men with early IP. Psychological distress was predicted by younger age, specific coping strategies and high levels of pain.

Lim AY, Gaffney K, Scott DG. · Rheumatology Department, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK. · Rheumatology (Oxford). · Pubmed #15901903 links to  free full text

Abstract: OBJECTIVE: To ascertain the extent of methotrexate (MTX)-related pancytopenia at the Norfolk and Norwich University Hospital (NNUH) between 1999 and 2004. METHODS: Patients were identified by a department database search, review of pharmacy records and personal communication. Pancytopenia was defined as white blood cell count (WBC) <3.5 x 10(9)/l, haemoglobin (Hb) <11 g/dl and platelet count <130 x 10(9)/l. Severe pancytopenia was defined as WBC <2.0 x 10(9)/l, Hb <10 g/dl and platelet count <50 x 10(9)/l. RESULTS: Twenty-five patients had MTX-induced pancytopenia. Eleven patients were taking folic acid and one folinic acid. The median dose of MTX was 12.5 mg weekly (interquartile range 5.625 mg) and median duration of treatment 36 months (interquartile range 40.5 months). The severity of pancytopenia correlated with the dose (P = 0.04). The numbers of patients with potential risk factors were: renal insufficiency, 8; pre-existing folate deficiency, 7; age >75 yr, 15; hypoalbuminaemia, 18; pre-existing infection with hip prosthesis, 1; possible drug interactions, 18; dosing errors, 1; and polypharmacy, 15. Pancytopenia was detected by routine blood monitoring in nine patients. There were seven deaths (28% mortality), five from sepsis and two from acute myeloid leukaemia. CONCLUSION: This is the largest reported individual case series of MTX-induced pancytopenia. With the increasing long-term use of MTX, it is important that patients be monitored for haematological side-effects as pancytopenia can be a late manifestation. Pharmacogenetics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.

Ostor AJ, Crisp AJ, Somerville MF, Scott DG. · Department of Rheumatology, Addenbrooke's Hospital, Cambridge CB2 2QQ. · BMJ. · Pubmed #15564258 links to  free full text

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Watts RA, Mooney J, Lane SE, Scott DG. · Department of Rheumatology, Ipswich Hospital NHS Trust, Heath Road, Ipswich IP4 5PD, UK. · Rheumatology (Oxford). · Pubmed #15126674 links to  free full text

Abstract: BACKGROUND: Systemic rheumatoid vasculitis (SRV) is a relatively rare complication of RA. The incidence of SRV appeared to increase during the 1970s and 1980s from 6.0 to 12.5/million. During the 1990s there have been major changes in the treatment of RA, with more aggressive control of inflammation. Our aim was to study the epidemiology of SRV in a stable, well-defined population over a 15-yr period. METHODS: Since 1988 we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset SRV, as defined by the criteria of Scott and Bacon, and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2002 were identified. The population in 2002 was estimated to be 445 000 (215 000 males). RESULTS: Fifty-one patients (24 male) with SRV were identified, with median age 61 yr and disease duration 16.8 yr. The overall annual incidence was 7.9/million (95% CI 5.9-10.4) (males, 7.7/million; females, 8.1/million). During the first quinquennium (1988-92) the incidence was 11.6/million (95% CI 7.4-17.0) and during the third (1998-2002) it was 3.6/million (95% CI 1.6-7.1). A rolling 3-yr average showed that the peak incidence was in 1992-94, at 15.2/million (95% CI 9.1-23.8), and the nadir was in 1998-2000, at 3.0/million (95% CI 0.8-7.8). A similar pattern was seen for males and females. There was no difference in age or disease duration at onset of SRV between the three quinquennia. CONCLUSIONS: The incidence of SRV has declined dramatically since the 1980s. This could be due to better control of inflammatory disease or changes in smoking habits.

Silman A, Symmons D, Scott DG, Griffiths I. · ARC Epidemiology Unit, University of Manchester, UK. · Ann Rheum Dis. · Pubmed #14532144 links to  free full text

Abstract: The British Society for Rheumatology (BSR) established a register of patients newly treated with biological agents, the BSR Biologics Register (BSRBR), which became active in January 2002. The goal is to register all patients in the United Kingdom with rheumatic diseases, newly starting treatment with these agents and to follow them up to determine the incidence of any short and long term hazards to health. The Register is also recruiting a comparison cohort of patients with rheumatoid arthritis treated with standard disease modifying antirheumatic drugs to determine the relative contributions of disease factors and other treatments apart from biological agents on any risks observed.

Cooper NJ, Mugford M, Symmons DP, Barrett EM, Scott DG. · Department of Epidemiology and Public Health, University of Leicester, Leicester, UK. · Rheumatology (Oxford). · Pubmed #12096226 links to  free full text

Abstract: OBJECTIVE: To estimate the health service, non-health service and total costs and predictors of costs in individuals with early inflammatory polyarthritis (IP). METHODS: We conducted a prospective longitudinal study over a 6-month period. The participants were a random sample of 133 individuals who had enrolled with the community-based Norfolk Arthritis Register (NOAR) database between 1994 and 1999. The main outcome measures were the mean (per person) 6-month health service cost, non-health-service cost and total cost associated with IP. RESULTS: One hundred and fifteen of the 133 individuals who were recruited into the study completed 6 months of follow-up. The mean 6-month total cost was estimated to be 2800 pounds sterling per person, of which 14% was health service costs and the remainder non-health-service costs. Higher total costs were associated with lower health status and rheumatoid factor positivity. CONCLUSIONS: Early IP has a considerable impact on both the health-care system and, more importantly, society. Non-health-service costs (i.e. costs incurred by the individual with the disease, their family and friends) account for a substantial proportion (86%) of the total costs associated with early IP.

Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ. · University of Manchester Medical School, Manchester, UK. · Arthritis Rheum. · Pubmed #11953966 No free full text.

Abstract: 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.

Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ. · ARC Epidemiology Unit, University of Manchester Medical School, Oxford Road, Manchester M13 9PT, UK. · Rheumatology (Oxford). · Pubmed #11934959 links to  free full text

Abstract: 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.

Wiles NJ, Scott DG, Barrett EM, Merry P, Arie E, Gaffney K, Silman AJ, Symmons DP. · ARC Epidemiology Unit, University of Manchester Medical School, Oxford Road, Manchester M13 9PT, UK. · Ann Rheum Dis. · Pubmed #11557653 links to  free full text

Abstract: BACKGROUND: Treatment, and therefore outcome, of rheumatoid arthritis (RA) will improve in the next few years. However, improvement in outcome can only be judged against the probability of certain outcomes with current conventional treatment. AIM: To document the five year outcome of RA in the late 1990s. SETTING: Norfolk Arthritis Register (NOAR). DESIGN: Longitudinal observational cohort study. METHODS: 318 patients with recent onset inflammatory polyarthritis recruited by NOAR in 1990-91 completed five years of follow up. Four groups were assessed: the whole cohort, all those referred to hospital, those who satisfied criteria for RA at baseline, and those referred to hospital who satisfied criteria for RA at baseline. Outcome was assessed with a visual analogue scale for pain, the Health Assessment Questionnaire (HAQ), and the Short Form-36 (SF-36). RESULTS: Of the RA hospital attenders, 50% had a visual analogue scale pain score of 5 cm or less and an HAQ score of 1.125 or less. SF-36 scores were reduced in all domains. Results are presented as cumulative percentages. CONCLUSIONS: These results can be used for comparison and to set targets for improvement.

Bukhari M, Harrison B, Lunt M, Scott DG, Symmons DP, Silman AJ. · University of Manchester, UK. · Arthritis Rheum. · Pubmed #11407682 links to  free full text

Abstract: 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] 3.8-83), 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.

Harrison BJ, Silman AJ, Wiles NJ, Scott DG, Symmons DP. · ARC Epidemiology Unit, University of Manchester, UK. · Arthritis Rheum. · Pubmed #11229462 links to  free full text

Abstract: OBJECTIVE: Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA). In this study, we examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP). METHODS: We studied 486 patients with IP who were referred to the Norfolk Arthritis Register, of whom 323 (67%) satisfied the American College of Rheumatology 1987 criteria for RA. Smoking status was assessed at baseline. Disease outcome was assessed at 3 years, using measures of joint inflammation, functional disability, and radiologic damage. The influence of smoking on disease outcome was explored using logistic regression techniques, with patients who had never smoked as the referent group. Results are expressed as odds ratios (ORs), with their 95% confidence intervals (95% CIs). RESULTS: Current smokers were significantly more likely to be RF positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%). After 3 years, rheumatoid nodules were significantly more common in smokers (13%) compared with ex-smokers/never smokers (4%), a relationship which persisted after adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting for age and sex, current smokers had significantly fewer swollen joints (OR 0.61, 95% CI 0.37-0.98). However, smoking status had no influence on the development of erosions or functional disability. CONCLUSION: Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage.

Barrett EM, Scott DG, Wiles NJ, Symmons DP. · Norfolk Arthritis Register, St Michael's Hospital, Aylsham, Norfolk. · Rheumatology (Oxford). · Pubmed #11136885 links to  free full text

Abstract: OBJECTIVE: To establish the prevalence of work disability and predictors of change in employment status in patients with early rheumatoid arthritis (RA). SETTING: The Norfolk Arthritis Register (NOAR), a primary-care based inception cohort of patients with recent-onset inflammatory arthritis. METHODS: Two cohorts of patients notified to NOAR, who satisfied the 1987 ACR criteria for RA at the time of notification (baseline) and who were economically active at the time of RA symptom onset, were identified. Cohort 1 consisted of 160 patients with an onset of RA between 1989 and 1992, and was followed for a mean of 8.6 yr from symptom onset. For 110 of these cases, a control group, matched for age, gender and employment status at baseline, was identified from the local population. Their employment histories were compared in 1995. Cohort 2 consisted of 134 patients with an onset of RA between 1994 and 1997, and was followed for a mean of 4.1 yr from symptom onset. RESULTS: One-third of RA cohort 1 had stopped working on the grounds of ill health by 1995. The baseline health assessment questionnaire (HAQ) score was the most important predictor of work disability. These patients were 32 times more likely to stop work on health grounds than the matched controls. The rates for work disability for the RA cases 1, 2, 5 and 10 yr after symptom onset were 14, 26, 33 and 39% respectively. For cohort 2, the rates for work disability 1 and 2 yr from onset were 23 and 33% respectively. CONCLUSION: Work disability is an important outcome in RA patients of working age. Many people stop working very early in the disease process, often before they are referred to hospital or started on disease-modifying anti-rheumatic drugs. Although the peak rates for work disability are in the early years, people with RA continue to leave the work force several years after onset. Thus, the recent move to earlier, more aggressive treatment has had no effect on the rates of work disability.

Pipitone N, Jolliffe VA, Cauli A, Scott DG, Pitzalis C. · Rheumatology Unit, GKT, Guys, Kings and St Thomas Hospitals, School of Medicine and Dentistry, London and. Rheumatology Unit, Norfolk & Norwich Hospital, Norwich, Norfolk, UK. · Rheumatology (Oxford). · Pubmed #11085811 links to  free full text

Abstract: We describe a 62-yr-old male patient with primary hypogammaglobulinaemia (PH) who fulfilled the 1987 American Rheumatism Association/American College of Rheumatology revised diagnostic criteria for rheumatoid arthritis (RA) but, despite persistent symmetrical synovitis, did not develop erosions. Virology studies and blood and synovial fluid (SF) cultures were consistently negative; a search for crystals in the SF was unrevealing. Peripheral blood (PB) B cells were absent, whilst the PB CD3(+) cell count was normal. The ratio of naive (CD45RA(+)) to memory (CD45R0(+)) cells was also normal (1:1) but the CD4:CD8 ratio was reversed. To our knowledge, this is the first report which combines the immunophenotypic analysis of the PB with that of the SF and synovial membrane (SM). This confirmed the absence of B cells and the reversed CD4:CD8 ratio. However, as in other chronic arthropathies, the SF and SM cellular infiltrate consisted almost exclusively of memory T cells, consistent with the preferential localization of this subset to inflamed tissues. This case indicates that synovitis can proceed persistently in the absence of B cells and that the migratory mechanisms of T cells are not altered. However, the case suggests that the absence of B cells and negativity for rheumatoid factor, combined with an increased presence of CD8(+) (suppresser/cytotoxic) T cells in the joint, might contribute to the non-erosive nature of the synovitis.

Cooper NJ, Mugford M, Scott DG, Barrett EM, Symmons DP. · School of Health Policy and Practice, University of East Anglia, Norwich, England. · J Rheumatol. · Pubmed #10990221 No free full text.

Abstract: OBJECTIVE: To estimate the secondary health service care and second line drug costs (including drug monitoring costs) for a cohort of people with early inflammatory polyarthritis (IP) and the subgroup classified as having rheumatoid arthritis (RA) recruited to a population based register. METHODS: The study population consisted of 344 people with IP who had enrolled on the Norfolk Arthritis Register (NOAR) in 1990-91, an average of 24 weeks after onset of their symptoms. Utilizing resource use data from NOAR, augmented by unit cost data from other sources, the average (per person) and cumulative secondary care and second line drug costs were estimated for Years 1, 2, 3, 4, and 5 following registration with NOAR. RESULTS: The total secondary health service care and second line drug costs were 472,125 (338,704 for RA subgroup) (1990-91 prices) over the 5 year study period, with inpatient stays, outpatient visits, and second line drugs accounting for 58, 9, and 33%, respectively. Nineteen percent of the study population neither visited hospital nor were prescribed second line drugs. CONCLUSION: Overall, inpatient stay costs represented the largest proportion of secondary health service care and second line drug costs, making 21% of the total study cohort responsible for 80% of the total 5 year costs incurred.

Wiles N, Symmons DP, Harrison B, Barrett E, Barrett JH, Scott DG, Silman AJ. · University of Manchester Medical School, UK. · Arthritis Rheum. · Pubmed #10403260 links to  free full text

Abstract: OBJECTIVE: To examine the effect of delay between symptom onset and notification to an arthritis register and the effect of application of the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria in a cumulative manner on estimates of the incidence of rheumatoid arthritis (RA). METHODS: General practitioners and/or hospital consultants in the Norwich Health Authority, Norfolk, UK, notified the Norfolk Arthritis Register (NOAR) of all patients who had onset of inflammatory polyarthritis (swelling of > or =2 joints) during 1990. The patients were assessed within 2 weeks of notification and annually thereafter. The ACR 1987 criteria for RA were applied at each assessment. Age- and sex-specific incidence rates were calculated. RESULTS: If up to 12 months elapsed from symptom onset to notification to NOAR and the ACR criteria were applied at the baseline assessment, RA incidence estimates, age-adjusted to the population of England and Wales, were 30.8/100,000 for women and 12.7/100,000 for men. If up to 5 years elapsed from symptom onset to notification, these estimates rose by 45% for women and 36% for men. If up to 5 years elapsed between symptom onset and notification and the criteria were applied cumulatively, the estimates rose by 75% and 93% for women and men, respectively, compared with the 1-year data, reaching 54.0/100,000 for women and 24.5 per 100,000 for men. CONCLUSION: Accurate estimation of the incidence of RA requires long-term followup of patients who present with undifferentiated inflammatory polyarthritis. The highest age-adjusted estimates from this study are probably the best that are available.