Showing papers in "Annals of the Rheumatic Diseases in 2003"
TL;DR: The updated EULAR recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions.
Abstract: Objectives: To update the EULAR recommendations for management of knee osteoarthritis (OA) by an evidence based medicine and expert opinion approach. Methods: The literature search and guidelines were restricted to treatments for knee OA pertaining to clinical and/or radiological OA of any compartment of the knee. Papers for combined treatment of knee and other types of OA were excluded. Medline and Embase were searched using a combination of subject headings and key words. Searches for those treatments previously investigated were conducted for January 1999 to February 2002 and for those treatments not previously investigated for 1966 to February 2002. The level of evidence found for each treatment was documented. Quality scores were determined for each paper, an effect size comparing the treatment with placebo was calculated, where possible, and a toxicity profile was determined for each treatment modality. Results: 497 new publications were identified by the search. Of these, 103 were intervention trials and included in the overall analysis, and 33 treatment modalities were identified. Previously identified publications which were not exclusively knee OA in the initial analysis were rejected. In total, 545 publications were included. Based on the results of the literature search and expert opinion, 10 recommendations for the treatment of knee OA were devised using a five stage Delphi technique. Based on expert opinion, a further set of 10 items was identified by a five stage Delphi technique as important for future research. Conclusion: The updated recommendations support some of the previous propositions published in 2000 but also include modified statements and new propositions. Although a large number of treatment options for knee OA exist, the evidence based format of the EULAR Recommendations continues to identify key clinical questions that currently are unanswered.
2,037 citations
TL;DR: The prevalence of systemic sclerosis associated pulmonary arterial hypertension in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies.
Abstract: Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. Methods: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of >35 mm Hg, carbon monoxide transfer factor (Tlco) 20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. Results: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure—raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3). Conclusions: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation.
710 citations
TL;DR: Smokers of both sexes have an increased risk of developing seropositive, but not seronegative, RA, which occurs after a long duration, but merely a moderate intensity, of smoking and may remain for several years after smoking cessation.
Abstract: randomly selected from the study base. Self reported smoking habits among cases and controls, and rheumatoid factor status among cases were registered. The incidence of RA in current smokers, ex-smokers, and ever-smokers, respectively, was compared with that of never-smokers. Results: Current smokers, ex-smokers, and ever-smokers of both sexes had an increased risk for sero- positive RA (for ever-smokers the odds ratio was 1.7 (95% confidence interval (95% CI) 1.2 to 2.3) for women, and 1.9 (95% CI 1.0 to 3.5) for men), but not for seronegative RA. The increased risk was only apparent among subjects who had smoked >20 years, was evident at an intensity of smoking of 6-9 cigarettes/day, and remained for up to 10-19 years after smoking cessation. The risk increased with increasing cumulative dose of smoking. Conclusion: Smokers of both sexes have an increased risk of developing seropositive, but not seronegative, RA. The increased risk occurs after a long duration, but merely a moderate intensity, of smoking and may remain for several years after smoking cessation.
623 citations
TL;DR: The British Society for Rheumatology established a register of patients newly treated with biological agents, the BSR Biologics Register (BSRBR), which became active in January 2002 and is recruiting a comparison cohort of patients with rheumatoid arthritis treated with standard disease modifying antirheumatic drugs.
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.
585 citations
TL;DR: Reduction of the number of entheses from 66 to 13 and omitting grading of the intensity of pain resulted in an index which was named the “Maastricht Ankylosing Spondylitis Enthesitis Score” (MASES), which seems to be a good alternative to the MEI with much better feasibility.
Abstract: Objective: To assess, firstly, the validity of the enthesis index published by Mander (Mander enthesis index (MEI)) and, secondly, to investigate whether it is possible to define a new enthesis index that is less time consuming to perform with at least similar or better properties. Methods: Data from the OASIS cohort, an international, longitudinal, observational study on outcome in ankylosing spondylitis, were used. In this study, measures of disease activity, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the MEI, were assessed regularly in 217 patients. With the MEI, for each measurement period independently, a process of data reduction was performed to identify the entheses most commonly reported as painful by the patients. A more concise enthesis index was constructed with aid of the entheses found in this way. Correlations with measures of disease activity were used to test the validity of several entheses indices. Results: Reduction of the number of entheses from 66 to 13 and omitting grading of the intensity of pain resulted in an index which was named the “Maastricht Ankylosing Spondylitis Enthesitis Score” (MASES). The MASES (range 0–13) has much greater feasibility than the MEI (range 0–90). However, up to 21% of patients with a score >0 on the MEI were not identified by a score on the MASES >0. Only 2.1% of the patients with an original enthesis score >0 had an original score on the MEI >3 (range 0–90) and it can be questioned whether a low score on the MEI index represents clinically important enthesitis. The Spearman correlation coefficient between the MASES score and the MEI was 0.90 and between the MASES and the BASDAI was 0.53 compared with a correlation of 0.59 between the MEI and the BASDAI. Conclusions: MASES seems to be a good alternative to the MEI with much better feasibility.
572 citations
TL;DR: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995 and the main predictors of severe ExRA were smoking at RA diagnosis and early disability.
Abstract: Objective: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. Methods: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955–94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1–42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. Results: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmo, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. Conclusion: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.
569 citations
TL;DR: BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease, and raise the possibility of a novel therapeutic approach in human SS.
Abstract: Background: Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis. Objective: To determine the level of BLyS in serum from patients with primary’s Sjogren’s syndrome (SS), another autoimmune disease in which B cell activation is high. Methods: Serum samples from 49 patients with primary SS according to the revised European criteria were assayed for BLyS, quantitative immunoglobulins, and autoantibody levels and compared with samples from 47 healthy control subjects. Results: The median level of BLyS was 5.99 ng/ml (25th-75th centile range 3.20‐8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range 1.96‐2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients with SS, the presence of anti-SSA antibodies was associated with significantly higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS in three patients with a monoclonal gammopathy was higher than in the other patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were associated with higher levels of gammaglobulins and IgG. There was a strong correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). Conclusion: In human SS the level of BLyS correlates with the level of autoantibodies. Thus, BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease. These findings raise the possibility of a novel therapeutic approach in human SS.
564 citations
TL;DR: The ASQoL provides a valuable tool for assessing the impact of interventions for ankylosing spondylitis and for evaluating models of service delivery and has excellent scaling and psychometric properties.
Abstract: Background: Although disease-specific health status measures are available for ankylosing spondylitis (AS), no instrument exists for assessing quality of life (QoL) in the condition.
Objective: To produce an AS-specific QoL measure that would be relevant and acceptable to respondents, valid, and reliable.
Methods: The ASQoL employs the needs-based model of QoL and was developed in parallel in the UK and the Netherlands (NL). Content was derived from interviews with patients in each country. Face and content validity were assessed through patient field test interviews (UK and NL). A postal survey in the UK produced a more efficient version of the ASQoL, which was tested for scaling properties, reliability, internal consistency, and validity in a further postal survey in each country.
Results: A 41 item questionnaire was derived from interview transcripts. Field testing interviews confirmed acceptability. Rasch analysis of data from the first survey (n=121) produced a 26 item questionnaire. Rasch analysis of data from the second survey (UK: n=164; NL: n=154) showed some item misfit, but showed that items formed a hierarchical order and were stable over time. Problematic items were removed giving an 18 item scale. Both language versions had excellent internal consistency (α=0.89–0.91), test-retest reliability (rs=0.92 UK and rs=0.91 NL), and validity.
Conclusions: The ASQoL provides a valuable tool for assessing the impact of interventions for AS and for evaluating models of service delivery. It is well accepted by patients, taking about four minutes to complete, and has excellent scaling and psychometric properties.
512 citations
TL;DR: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage.
Abstract: Objective: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA).
Methods: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde.
Results:Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years.
Conclusion: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.
475 citations
TL;DR: An international consensus about the use of anti-tumour necrosis factor α (anti-TNFα) for treating patients with ankylosing spondylitis is obtained and may be used for guidance in clinical decision making and as the basis for the development of guidelines.
Abstract: Objective: To obtain an international consensus about the use of anti-tumour necrosis factor α (anti-TNFα) for treating patients with ankylosing spondylitis (AS). Methods: These recommendations were developed by a review of published reports in combination with expert opinion, including a Delphi exercise, and a consensus meeting of the ASsessments in AS (ASAS) Working Group. Results: The final consensus comprises the following requirements: (1) For the initiation of anti-TNFα therapy: ( a ) a diagnosis of definitive AS; ( b ) presence of active disease for at least four weeks as defined by both a sustained Bath AS Disease Activity Index (BASDAI) of at least 4 and an expert opinion based on clinical features, acute phase reactants, and imaging modalities; ( c ) presence of refractory disease defined by failure of at least two non-steroidal anti-inflammatory drugs during a single three month period, failure of intra-articular steroids if indicated, and failure of sulfasalazine in patients with peripheral arthritis; ( d ) application and implementation of the usual precautions and contraindications for biological therapy. (2) For the monitoring of anti-TNFα therapy: both the BASDAI and the ASAS core set for clinical practice should be followed regularly. (3) For the discontinuation of anti-TNFα therapy: in non-responders, consideration should be made after 6–12 weeks’ treatment. Response is defined as improvement of ( a ) at least 50% or 2 units (on a 0–10 scale) of the BASDAI, ( b ) expert opinion that treatment should be continued. Conclusion: This consensus statement on anti-TNFα treatment in AS may be used for guidance in clinical decision making and as the basis for the development of guidelines. Evaluation of the healthcare consequences of this consensus is subject to further research by the ASAS group.
411 citations
TL;DR: Dual 5-LOX/COX inhibitors act by blocking the formation of both prostaglandins and leucotrienes but do not affect lipoxin formation, which avoids some of the disadvantages of selective COX-2 inhibitors and spares the gatrointestinal mucosa.
Abstract: Dual 5-LOX/COX inhibitors are potential new drugs to treat inflammation. They act by blocking the formation of both prostaglandins and leucotrienes but do not affect lipoxin formation. Such combined inhibition avoids some of the disadvantages of selective COX-2 inhibitors and spares the gatrointestinal mucosa.
TL;DR: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose, and the role of some traditional risk factors, such as age and hypertension, was confirmed.
Abstract: Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE).
Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-s2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed.
Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT.
Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.
TL;DR: A number of antimicrobial peptides such as defensins have multiple functions in host defence, which endows them with the capacity to marshall adaptive host defences against microbial invaders.
Abstract: A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell lining of the gastrointestinal and genitourinary tracts, the tracheobronchial tree, and keratinocytes. Some are produced constitutively, whereas others are induced by proinflammatory cytokines and exogenous microbial products. Defensins produced by cells in the course of innate host defence serve as signals which initiate, mobilise, and amplify adaptive immune host defences. Administration of defensins with antigens to mice enhances both cellular (Th1-dependent) and humoral (Th2-dependent) cytokine production and immune responses. Linkage of defensins to weak tumour antigens potentiates their immunoadjuvant effects. Defensins use multiple cellular receptors, which endows them with the capacity to marshall adaptive host defences against microbial invaders.
TL;DR: Functional gains were achieved with both exercise programmes compared with the control group, and left and right quadriceps strength was also significantly better than in the hydrotherapy group.
Abstract: Objective: To compare the effects of a hydrotherapy resistance exercise programme with a gym based resistance exercise programme on strength and function in the treatment of osteoarthritis (OA). Design: Single blind, three arm, randomised controlled trial. Subjects: 105 community living participants aged 50 years and over with clinical OA of the hip or knee. Methods: Participants were randomised into one of three groups: hydrotherapy (n = 35), gym (n = 35), or control (n = 35). The two exercising groups had three exercise sessions a week for six weeks. At six weeks an independent physiotherapist unaware of the treatment allocation performed all outcome assessments (muscle strength dynamometry, six minute walk test, WOMAC OA Index, total drugs, SF-12 quality of life, Adelaide Activities Profile, and the Arthritis Self-Efficacy Scale). Results: In the gym group both left and right quadriceps significantly increased in strength compared with the control group, and right quadriceps strength was also significantly better than in the hydrotherapy group. The hydrotherapy group increased left quadriceps strength only at follow up, and this was significantly different from the control group. The hydrotherapy group was significantly different from the control group for distance walked and the physical component of the SF-12. The gym group was significantly different from the control group for walk speed and self efficacy satisfaction. Compliance rates were similar for both exercise groups, with 84% of hydrotherapy and 75% of gym sessions attended. There were no differences in drug use between groups over the study period. Conclusion: Functional gains were achieved with both exercise programmes compared with the control group.
TL;DR: The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.
Abstract: Objectives: To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases. Methods: 249 consecutive sera from an arthritis clinic sent for rheumatology testing were selected for testing with the anti-CCP2 assays and for the presence of rheumatoid factor (RF). Patient charts were reviewed for demographic information, clinical diagnosis, radiographic information, and other laboratory data. Results: The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 66.0% and 90.4%, respectively. This compared with the sensitivity and specificity of RF for RA at 71.6% and 80.3%. Furthermore, 10/29 (34%) RF− patients with RA demonstrated reactivity to CCP. The presence of either anti-CCP or RF increased testing sensitivity for diagnosis of RA to 81.4%; the presence of both RF and anti-CCP demonstrated a testing specificity similar to that of anti-CCP reactivity alone for the diagnosis of RA (91.1%). Conclusions: The detection of anti-CCP is useful for the diagnosis of RA, in fact even more so than RF, because of its higher specificity.
TL;DR: The author reviewed the different criteria that have been proposed for the classification of patients with Sjogren’s syndrome and commented on the US-European Consensus Group criteria, which were reported for the first time in this same issue.
Abstract: I read with great interest the editorial by R Manthorpe published in the June issue of the Annals of the Rheumatic Diseases .1 The author reviewed the different criteria that have been proposed for the classification of patients with Sjogren’s syndrome (SS) and, in particular, commented on the US-European Consensus Group criteria,2 which were reported for the first time in this same issue. As the first author of the paper, I would like to discuss certain points and criticisms which he raised about our criteria set. First of all I would like to discuss briefly the meaning of “classification criteria” and the methods by which the European3,4 and US-European criteria for SS2 were derived.
Classification criteria are not meant to be used for diagnosis. Diagnosis is an often complex process by which a doctor arrives at the suspicion of a specific disease in a given patient, and then must collect enough clinical data to confirm that suspicion. Classification criteria, on the other hand, represent a tool for research and communication, providing uniform criteria for the scientific community to classify patients with the same disease, select patients for clinical-therapeutic trials, and make the data obtained by different researchers in different series of patients comparable. As any experienced rheumatologist knows, it is not uncommon to diagnose a specific rheumatic disease in a patient who does not meet the classification criteria proposed for that disease.
Given these considerations we can argue that:
TL;DR: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course.
Abstract: Results: Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in ero- sions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease. Conclusion: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.
TL;DR: The results indicate that patients with RA, by adjusting to a Mediterranean diet, did obtain a reduction in inflammatory activity, an increase in physical function, and improved vitality.
Abstract: An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis
TL;DR: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels, which can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.
Abstract: Background: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory.
Objective: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account.
Methods: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial).
Results: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity.
Conclusion: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.
TL;DR: Health related quality of life was similar for patients and reference group except for function, where patients had worse function, and more pain preoperatively and higher age and postoperative low back pain predicted a worse outcome in WOMAC function.
Abstract: questions were asked at the final follow up. Results: 198/211 (94%) of the patients and 83/109 (76%) of the reference group participated at the final follow up. At follow up, the only difference between the two groups in the SF-36 was physical function, where patients scored worse. Patients also reported worse WOMAC function. 31% of the patients had improved by <10/100 WOMAC score points for pain and/or function at final follow up, compared with preoperatively. More pain preoperatively and higher age and postoperative low back pain predicted a worse outcome in WOMAC function. Conclusion: 3.6 years after THR for OA, health related quality of life was similar for patients and ref- erence group except for function, where patients had worse function. Higher age and more pain preoperatively predicted a poor outcome. Patients with hip OA with musculoskeletal comorbidities, such as low back pain and OA of the non-operated hip, have less long term functional improvement after THR.
TL;DR: Self reported musculoskeletal diseases are highly prevalent, with a fair to good reliability and a disease-specific pain pattern, and the coexistence of these diseases is high.
Abstract: Objectives: To present the prevalence of self reported musculoskeletal diseases, the coexistence of these diseases, the test-retest reliability with six months in between, and the association with musculoskeletal pain symptoms.
Methods: Twelve layman descriptions of common musculoskeletal diseases were part of the questionnaires of a prospective cohort study of a random sample in the general Dutch population aged 25 years or more (baseline: n=3664, follow up after six months: n=2338). Data collection also included information about pain relating to five different anatomical areas.
Results: Osteoarthritis of the knee (men 10.1%, women 13.6%) was amongst the most reported musculoskeletal diseases, whereas the figures for self reported rheumatoid arthritis (RA) were 1.6% and 4.6% for men and women, respectively. The coexistence of these diseases is high: 47 of the 66 combinations were reported more often than would be expected if they were independent of each other (p<0.05). For most diseases the test-retest reliability was good (κ between 0.6 and 0.8), but for repetitive strain injury (κ=0.37) and chronic arthritis other than RA (κ=0.44) the agreement was fair to moderate. All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases, and the pain pattern was disease-specific.
Conclusions: Self reported musculoskeletal diseases are highly prevalent, with a fair to good reliability and a disease-specific pain pattern. Health surveys are a limited but valuable source of information for this group of health problems, which is not available from most other sources of information.
TL;DR: There is an association between smoking and report of regional pain, which is apparent even in ex-smokers, and people with a low threshold for reporting pain and disability are more likely to take up and continue smoking.
Abstract: Objectives: To explore the relation between smoking habits and regional pain in the general population.
Methods: A questionnaire was mailed to 21 201 adults, aged 16–64 years, selected at random from the registers of 34 British general practices, and to 993 members of the armed services, randomly selected from pay records. Questions were asked about pain in the low back, neck, and upper and lower limbs during the past 12 months; smoking habits; physical activities at work; headaches; and tiredness or stress. Associations were examined by logistic regression and expressed as prevalence ratios (PRs).
Results: Questionnaires were completed by 12 907 (58%) subjects, including 6513 who had smoked at some time, among whom 3184 were current smokers. Smoking habits were related to age, social class, report of headaches, tiredness or stress, and manual activities at work. After adjustment for potential confounders, current and ex-smokers had higher risks than lifetime non-smokers for pain at all of the sites considered. This was especially so for pain reported as preventing normal activities (with PRs up to 1.6 in current v never smokers). Similar associations were found in both sexes, and when analysis was restricted to non-manual workers.
Conclusions: There is an association between smoking and report of regional pain, which is apparent even in ex-smokers. This could arise from a pharmacological effect of tobacco smoke (for example, on neurological processing of sensory information or nutrition of peripheral tissues); another possibility is that people with a low threshold for reporting pain and disability are more likely to take up and continue smoking.
TL;DR: For patients with insufficient efficacy from etanercept, treatment with infliximab provided better results, suggesting that a trial of inflIXimab is reasonable for such patients, and data provide support for atrial of the reciprocal TNFalpha blocker in patients when one such agent has failed.
Abstract: Objective: When one TNFα blocker (etanercept or infliximab) has failed, to determine whether it makes sense to treat patients with the other.
Patients and methods: Since 1999 patients treated with etanercept or infliximab have been systematically followed up at our institution in the STURE database. We identified 31 patients who had received both agents.
Results: Eighteen patients received etanercept first; discontinuation was mostly due to lack of efficacy. DAS28 values had improved only slightly with etanercept, with a mean (SEM) best DAS28 value of 4.8 (0.6). After switching to infliximab, the mean best DAS28 was 3.6 (0.6)—significantly better than the previous result (p<0.05). Similarly, the mean best ACR-N during etanercept treatment was 17.2 (6.65) and during subsequent infliximab treatment 40.4 (10.6) (p = 0.08). Thirteen patients received infliximab first; discontinuation was mainly due to adverse events. The best DAS28 value achieved during etanercept was 3.6 (0.4) compared with 4.1 (0.4) for infliximab (p<0.05), but the change in DAS28 was not different and ACR-N were similar for infliximab and etanercept in this group.
Conclusion: For patients with insufficient efficacy from etanercept, treatment with infliximab provided better results, suggesting that a trial of infliximab is reasonable for such patients. For patients who discontinued infliximab owing to adverse events, treatment with etanercept gave at least similar clinical efficacy. Taken together, these data provide support for a trial of the reciprocal TNFα blocker in patients when one such agent has failed.
TL;DR: In this paper, a double blind, placebo controlled, phase Ib clinical trial with a specific, oral CCR1 antagonist was carried out, where 16 patients with active rheumatoid arthritis (RA) were randomised 3:1 to active:placebo treatment for 14 days.
Abstract: Background: Chemokines and their receptors are considered important contributors in cell migration and inflammation in chronic inflammatory disorders. Chemokines affecting monocytes/macrophages are considered potential therapeutic targets, but no studies of the effects of blocking the chemokine repertoire in humans with a chronic inflammatory disease have been reported.
Objective: To carry out a double blind, placebo controlled, phase Ib clinical trial with a specific, oral CCR1 antagonist.
Methods: 16 patients with active rheumatoid arthritis (RA) were randomised 3:1 to active:placebo treatment for 14 days. Synovial biopsy specimens were obtained on days 1 and 15. Immunohistochemistry was used to detect the presence of various cell types before and after treatment and the results measured by digital image analysis. Results before and after treatment were compared by paired t test, and a two sample t test was used to compare the changes from baseline in the two groups.
Results: All patients completed the study. A significant reduction in the number of macrophages (p=0.016), intimal macrophages (p=0.026), and CCR1+cells (p=0.049) in patients treated with the chemokine antagonist compared with the placebo group occurred in the synovium. Significant decreases in overall cellularity, intimal lining layer cellularity, CD4+ T cells, and CD8+ T cells also occurred in treated patients. Cells lacking CCR1 were not affected. Trends towards clinical improvement were seen in the treated patients but not in the placebo group. Severe side effects were not reported.
Conclusion: Specific chemokine receptor blockade can result in relevant biological effects in patients with active RA.
TL;DR: Many infections have been found to be associated with antiphospholipid antibodies (aPL), although a pathogenic role for these antibodies has not usually been obvious except in a few isolated cases.
Abstract: Many infections have been found to be associated with antiphospholipid antibodies (aPL), although a pathogenic role for these antibodies has not usually been obvious except in a few isolated cases. Two types of aPL have been referred to as "autoimmune" and "infectious" types. This distinction, however, has subsequently been found not to be absolute.
TL;DR: Findings suggest that TNFα antagonists merit further study for the treatment of RA in HCV infected patients, and larger and longer term studies are still needed.
Abstract: Background: Tumour necrosis factor α (TNFα) antagonists are effective for the treatment of rheumatoid arthritis (RA), but concerns remain about the safety of these agents in the presence of chronic infections, including hepatitis C virus (HCV) infection.
Objective: To examine the influence of treatment with TNFα antagonists on levels of HCV viraemia and serum transaminases in patients with RA and HCV.
Methods: In a retrospective survey the course of 16 HCV infected patients with RA who had received the TNFα antagonists etanercept or infliximab was analysed. Eight additional patients with RA and HCV were also enrolled into a three month prospective trial of etanercept. Serum concentrations of albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and HCV were followed.
Results: Viraemia was measured in 22 patients receiving a TNFα antagonist at the start of treatment and after 1–34 months (median 9 months follow up). Twenty four patients had serial tests of liver related enzymes and albumin. None of the differences between liver related tests at baseline and at follow up achieved significance (p>0.05). Similarly, the mean HCV measurement at 1–3, 4–6, 7–12, and 13–34 months did not differ significantly from baseline (p>0.05).
Conclusion: In this study, liver related blood tests and HCV viral load measurements did not change substantially. These findings suggest that TNFα antagonists merit further study for the treatment of RA in HCV infected patients. Larger and longer term studies are still needed.
TL;DR: Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs, and the proportion of extra-articular manifestations is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.
Abstract: Objectives: To characterise RA in a sample of Spanish patients by estimating mean clinical activity, functional ability, and radiological damage, and current and cumulative prevalence of extra-articular manifestations. Methods: Cross sectional analysis of a cohort of patients with RA randomly selected from the clinical databases of 34 centres. Standard definitions and measurements were used, and radiographs read centrally. Estimates and confidence intervals were adjusted to sampling. Results: Data were available for 788 patients. Extra-articular RA was present in 285 (36.2%) patients. Cumulative prevalence and 95% confidence intervals of extra-articular manifestations were estimated: nodules 24.5% (21.5 to 27.5), Sjogren’s syndrome 17.0% (14.4 to 19.6), atlantoaxial subluxation 12.1% (9.8 to 14.4), carpal tunnel syndrome 10.7% (7.8 to 13.6), interstitial lung disease 3.7% (2.4 to 5.0), serositis 2.5% (1.4 to 3.5), eye disease 2.5% (1.1 to 3.9), vasculitis 1.3% (0.5 to 2.1), amyloidosis 0.6% (0.1 to 1.2), and Felty’s syndrome 0.3% ( Conclusion: Spanish patients with RA ever seen by a rheumatologist have, on average, a moderate degree of activity, despite widespread use of DMARDs. Measures of the degree of progression do not show a benign disease. The proportion of extra-articular manifestations in Spanish patients with RA is similar to that found in other Mediterranean populations, and lower than that reported in Anglo Saxon countries.
TL;DR: The impact on several dimensions of health related QOL in patients with RA and AS of working age under rheumatological care was comparable and, after disease characteristics, was the most important determinant.
Abstract: Objective: To investigate the relationship between work and quality of life (QOL) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) aged 16-59. Methods: 1056 patients with RA and 658 with AS were included in the study. Data were obtained by postal questionnaire, which included severa generic and disease related QOL instruments. Separate dimensions and physical and mental summary scores from the SF-36 were compared. Stepwise multiple regression was performed to study the relationship between work and physical and mental health related QOL, including disease related factors, coping, and fatigue. Results: Physical health related QOL was reported to be worse, and mental health related QOL better, in RA than in AS in people of working age. No differences between RA and AS were found in somatic pain, physical role functioning, social functioning, emotional role functioning, vitality, or general health perception; nor were there any significant differences in fatigue and behavioural coping styles. Work was positively associated with physical health related QOL in both groups and, after disease characteristics, was the most important determinant. No association was found with mental health related QOL. Conclusions: Although physical health related QOL was worse in patients with RA, the impact on several dimensions of health related QOL in patients with RA and AS of working age under rheumatologica care was comparable. Patients with RA and AS experienced similar limitations in physical role functioning, including work. Work is an important independent external determinant of physical health related QOL, but not of mental health related QOL.
TL;DR: MTX toxicity, final dose, and efficacy are influenced by folate supplementation, and baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.
Abstract: Objective: To study factors associated with toxicity, final dose, and efficacy of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Methods: Data were used from a randomised clinical 48 week trial on 411 patients with RA all treated with MTX, comparing folates and placebo. Logistic regression was used to study the relation between baseline variables and various dependent factors, including hepatotoxicity (alanine aminotransferase ⩾3×upper limit of normal), MTX withdrawal, final MTX dose ⩾15 mg/week, and MTX efficacy. Results: Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity. Next to this, high body mass index was related to the occurrence of hepatotoxicity. Prior gastrointestinal (GI) events and younger age were related to the adverse event, diarrhoea. Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal, which in turn was associated with the absence of folate supplementation, body mass index, prior GI events, and female sex. Renal function (creatinine clearance ⩾50 ml/min) was not associated with toxicity. Reaching a final dose of MTX of ⩾15 mg/week was related to folate supplementation and the absence of prior GI events. Efficacy of MTX treatment was associated with low disease activity at baseline, male sex, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lower creatinine clearance. Conclusions: MTX toxicity, final dose, and efficacy are influenced by folate supplementation. Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.
TL;DR: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.
Abstract: Objectives: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). Methods: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. Results: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p⩽0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p⩽0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p⩽0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p⩽0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo. Conclusions: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.