Rheumatoid Arthritis: Devlin J

Devlin J, Wagstaff K, Arthur V, Emery P. · Rheumatism and Rehabilitation Research Unit, University of Leeds, UK. · Rheumatology (Oxford). · Pubmed #10325668 links to  free full text

Abstract: OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, Anonymous00244. · Hospital de Gran Canaria Dr, Negrin, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n 35011, Spain. · Arthritis Res Ther. · Pubmed #18325087 links to  free full text

Abstract: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Mattey DL, Thomson W, Ollier WE, Batley M, Davies PG, Gough AK, Devlin J, Prouse P, James DW, Williams PL, Dixey J, Winfield J, Cox NL, Koduri G, Young A. · University Hospital of North Staffordshire, Stoke-on-Trent, UK. · Arthritis Rheum. · Pubmed #17469097 links to  free full text

Abstract: OBJECTIVE: To determine whether the HLA-DRB1 shared epitope (SE) is associated with early mortality and specific causes of death in rheumatoid arthritis (RA). METHODS: HLA-DRB1 genotyping was carried out on blood samples from 767 patients recruited for the Early RA Study (ERAS), a multicenter, inception cohort study with followup over 18 years. Dates and causes of death (n = 186) were obtained from the Office of National Statistics. The association of HLA-DRB1 alleles with risk of mortality was assessed using Cox proportional hazards regression analyses. Multivariate stepwise models were used to assess the predictive value of HLA-DRB1 genotypes compared with other potential baseline risk factors. RESULTS: The SE was not significantly associated with overall mortality. However, the presence of 2 SE alleles was associated with risk of mortality from ischemic heart disease (hazard ratio [HR] 2.02 [95% confidence interval 1.04-3.94], P = 0.04), and malignancy (HR 2.18 [95% confidence interval 1.17-4.08], P = 0.01). Analysis of specific SE genotypes (corrected for age and sex) revealed that the HLA-DRB1*0101/*0401 and 0404/*0404 genotypes were the strongest predictors of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively), and DRB1*0101/*0401 showed a possible interaction with smoking. Male sex, erythrocyte sedimentation rate, and Carstairs Deprivation Index were also predictive, but the Health Assessment Questionnaire score, rheumatoid factor, nodules, and swollen joint counts were not. Mortality due to malignancy was particularly associated with DRB1*0101 genotypes. CONCLUSION: The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA-DRB1 genotypes with particular homozygous and compound heterozygous SE combinations.

Quinn MA, Gough AK, Green MJ, Devlin J, Hensor EM, Greenstein A, Fraser A, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Chapel Allerton Hospital, Chapeltown Road, Leeds LS74SA, UK. · Rheumatology (Oxford). · Pubmed #16287917 links to  free full text

Abstract: OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls. METHODS: One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.

Green MJ, Gough AK, Devlin J, Smith J, Astin P, Taylor D, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, Leeds, UK. · Rheumatology (Oxford). · Pubmed #12509618 links to  free full text

Abstract: OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.

Young A, Dixey J, Kulinskaya E, Cox N, Davies P, Devlin J, Emery P, Gough A, James D, Prouse P, Williams P, Winfield J. · Rheumatology Unit, City Hospital, St Albans, Herts AL3 5PN, UK. · Ann Rheum Dis. · Pubmed #11874837 links to  free full text

Abstract: OBJECTIVES: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). SETTING: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. PATIENTS: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. METHODS: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. OUTCOME MEASURES: Changes in, and loss of paid work by five years' follow up. RESULTS: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. CONCLUSIONS: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Young A, Dixey J, Cox N, Davies P, Devlin J, Emery P, Gallivan S, Gough A, James D, Prouse P, Williams P, Winfield J. · City Hospital, St Albans AL3 5PN, UK. · Rheumatology (Oxford). · Pubmed #10888704 links to  free full text

Abstract: OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives. METHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Devlin J, Gough A, Huissoon A, Perkins P, Jubb R, Emery P. · Rheumatology and Rehabilitation Research Unit, Leeds, UK. · Clin Rheumatol. · Pubmed #10791615 No free full text.

Abstract: The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation.

Njeh CF, Boivin CM, Gough A, Hans D, Srivastav SK, Bulmer N, Devlin J, Emery P. · Department of Nuclear Medicine, Queen Elizabeth Hospital, Birmingham, UK. · Osteoporos Int. · Pubmed #10367033 No free full text.

Abstract: Osteoporosis associated with active rheumatoid arthritis (RA) has been demonstrated in both the axial and peripheral skeleton, especially the periarticular regions more directly affected by the disease. Quantitative ultrasound (QUS) is a recently accepted tool for the assessment of bone status, and therefore could be used to monitor bone changes in RA patients. In a cross-sectional study we measured ultrasound velocity (Ad-SOS) through the proximal phalanges in three groups of female subjects. These included: 51 patients with rheumatoid arthritis (group 1), 44 general practitioner (GP)-referred patients for osteopenia (group 2) and 52 young healthy volunteers (group 3). For groups 1 and 2 bone mineral density (BMD) of the lumbar spine and proximal femur were also measured. For the RA patients BMD of the hand, measurement of hand function (HAQ and grip strength) and disease activity (ESR and CRP) were also assessed. The precision of long-term Ad-SOS measurements on volunteers gave a root mean square coefficient of variation (CV) of 0.7% and standardized CV of 3.6%. No statistically significant effect of dominance was observed in the measured Ad-SOS between the dominant and non-dominant hand (r = 0.96, p < 0.001). Ad-SOS was found to be significantly different in the three groups (p < 0.0001). Ad-SOS was highly dependent on age (r = -0.67), with a gradual reduction (-5.2 m/s per year) after the age of 30 years for female patients in both group 1 and group 2. Ad-SOS was significantly correlated with lumbar spine, femoral neck and hand BMD, with correlation coefficients of 0.49, 0.51 and 0.72 respectively for RA patients. Finger ultrasound was moderately correlated with measures of hand function, with coefficients of 0.37 and 0.39 for HAQ and grip strength respectively. Hand BMD also correlated to the same power with these parameters. Neither finger ultrasound nor BMD was significantly correlated with ESR and CRP (measures of disease activity). We have demonstrated that bone status can be assessed quickly and cheaply using a portable QUS device. Ad-SOS relates to the measure of hand function in RA patients. Longitudinal studies are required to determine the usefulness of finger ultrasound for monitoring disease progression or the effect of treatment in RA.

Pease CT, Bhakta BB, Devlin J, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, UK. · Rheumatology (Oxford). · Pubmed #10325661 links to  free full text

Abstract: OBJECTIVE: To identify factors affecting prognosis in patients with late-onset rheumatoid arthritis (RA). METHODS: A total of 400 patients with RA fulfilling the American College of Rheumatology criteria for diagnosis were prospectively recruited from two hospital rheumatology centres. Of these patients, 214 had disease onset above age 65 yr (LORA) and 186 below age 65 yr (YORA). Follow-up clinical, functional, laboratory and radiological assessments were compared. The Ritchie articular index (RAI) and joint erosions were used as markers of disease activity and damage, respectively. Disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). RESULTS: At median follow-up of 3.6 yr, the frequency of joint erosions was similar (YORA, 51.6%; LORA, 54.2%). The remission rate was greater in the LORA group (YORA, 20.4%; LORA, 45.8%, P < 0.01). Factors associated with the development of erosions were: IgM rheumatoid factor (RF) seropositivity [odds ratio (OR) = 4.24, 95% confidence interval (CI) 2.56, 6.94], HLA DR4 (OR = 2.07, 95% CI 1.28, 3.35) and elevated inflammatory markers (OR = 1.81, 95% CI 1.04, 3.14). Continuous steroid use >3 months for the LORA group was associated with increased erosions (OR = 4.09, 95% CI 1.81, 9.27). LORA patients (OR = 2.99, 95% CI 1.77, 5.02) were more likely to go into remission and IgM RF-seropositive patients less likely to go into clinical remission (OR = 0.47, 95% CI 0.28, 0.77). Female patients with a high HAQ score at presentation experienced a poor functional outcome (female OR = 3.01, 95% CI 1.59, 5.68; high HAQ OR = 3.02, 95% CI 1.98, 4.62). CONCLUSION: LORA can be as damaging as classical RA and joint erosions are often observed at presentation. Being RF seropositive, DR4 positive, and having elevated inflammatory markers at onset, were associated with poor radiological outcome irrespective of age of onset. Being female and having marked disability at presentation were associated with poor functional outcome in both groups. These findings suggest that treatment approaches used in classical YORA should be instituted with equal vigour in patients with LORA.