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ID PMID Title PublicationDate abstract
21243493 Long-term follow-up of adalimumab monotherapy for rheumatoid arthritis in Japanese patient 2012 Feb We present six cases of patients with Japanese rheumatoid arthritis (RA) treated with a tumor necrosis factor (TNF)-alpha blocking agent, adalimumab as monotherapy for 220 weeks. All six patients were women, and the median age was 54.0 ± 7.07 years old. The median duration of the disease was 7.43 ± 11.1 years, and the median disease activity score (DAS28-CRP) was 5.35 ± 0.69. Three of six patients were able to continue to receive this treatment for 220 weeks successfully, and the DAS28-CRP decreased to 1.89 ± 0.75. Two patients withdrew because of lack of efficacy, and one patient withdrew because of adverse events (non-Hodgkin lymphoma). Adalimumab resulted in a sustained clinical response in RA patients during 220-week follow-up.
20658292 Cold and heat pattern of rheumatoid arthritis in traditional Chinese medicine: distinct mo 2012 Jan The research is aimed to explore the distinct molecular signatures in discriminating the rheumatoid arthritis patients with traditional Chinese medicine (TCM) cold pattern and heat pattern. Twenty patients with typical TCM cold pattern and heat pattern were included. Microarray technology was used to reveal gene expression profiles in CD4+ T cells. The signal intensity of each expressed gene was globally normalized using the R statistics program. The ratio of cold pattern to heat pattern in patients with RA at more or less than 1:2 was taken as the differential gene expression criteria. Protein-protein interaction information for these genes from databases was searched, and the highly connected regions were detected by IPCA algorithm. The significant pathways were extracted from these subnetworks by Biological Network Gene Ontology tool. Twenty-nine genes differentially regulated between cold pattern and heat pattern were found. Among them, 7 genes were expressed significantly more in cold pattern. Biological network of protein-protein interaction information for these significant genes were searched and four highly connected regions were detected by IPCA algorithm to infer significant complexes or pathways in the biological network. Particularly, the cold pattern was related to Toll-like receptor signaling pathway. The following related pathways in heat pattern were included: Calcium signaling pathway; cell adhesion molecules; PPAR signaling pathway; fatty acid metabolism. These results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment.
22085488 Modulation of T cell proliferation and cytokine response by Plumbagin, extracted from Plum 2011 Nov 16 BACKGROUND: The extracts of Plumbago zeylanica have been used in China and other Asian countries as folk medicine for the treatment of cancer, rheumatoid arthritis and dysmenorrhoea. Effect of Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) purified from Plumbago zeylanica on Con A induced T cell proliferation was studied in spleen cells from collagen induced arthritic DBA/1 mice. METHODS: The DBA/1 mice (five per each group) were immunized with 0.1 mL of collagen (emulsified in CFA) by intradermal injection at the base of the tail. On day 20, mice were given a booster dose of collagen (emulsified in IFA) through the same route. Plumbagin was given at different concentrations (3.3, 6.6, 13.3 mg/kg body weight) intraperitoneally. Control mice received olive oil alone. The Con A induced T cell proliferative responses of arthritic and Plumbagin treated mice were studied by cell culture experiments using tritiated Thymidine. In addition the cytokine levels were estimated from the in vitro spleen culture supernatants of arthritic mice primed with different concentrations of Plumbagin by ELISA. RESULTS: Plumbagin enhanced the decreased Con A induced T cell proliferation and Interleukin-2 production in arthritic mice. Moreover elevated levels of IFN- γ were found to be decreased in Plumbagin treated spleen cell culture supernatants. Subclasses of IgG were found to be decreased by Plumbagin treatment, IgG2a reduction seems to be more prominent. CONCLUSION: The results obtained in the current study indicate that Plumbagin is very effective in the mechanism based treatment of Rheumatoid arthritis.
22004229 Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheuma 2011 Oct AIM: 1,25 dihydroxy vitamin D3 has immunomodulatory functions in rheumatoid arthritis (RA) and is an anti-osteoporotic agent. No studies exist to assess its pain-relieving action in RA. METHODS: An open-labeled randomized trial comparing triple disease-modifying anti-rheumatic drug (DMARD) therapy and 500 IU 1,25 dihydroxy vitamin D3 + calcium combination versus triple DMARD and calcium alone was conducted. The primary outcome was the time to pain relief by patients' visual analogue scale (VAS). Changes in VAS after first achievement of pain relief and after 3 months were noted. 25 hydroxy-vitamin D levels were correlated with disease activity scor (DAS-28), adjusting for sun exposure. Comparisons between the groups were done by Mann-Whitney test and independent samples test. RESULTS: Patients on the vitamin D group (n = 59) had higher pain relief than the control group (n = 62) (50%vs. 30%, P = 0.006). There was no significant difference in the time taken for initial pain relief between the two groups. Occurrence of hypovitaminosis D in RA patients (68.1%) is comparable to published normal Indian prevalence. There was no correlation between 25 hydroxy vitamin D levels and disease activity. CONCLUSIONS: Supplementation of 500 IU of 1,25 dihydroxy vitamin D3 daily to previously DMARD-naïve patients with early RA along with triple DMARD therapy results in a significantly higher pain relief at the end of 3 months. The number needed to treat for this additional pain relief was 5. The prevalence of vitamin D deficiency in the study population was 68.1%.
22679298 The ability of synovitis to predict structural damage in rheumatoid arthritis: a comparati 2013 May OBJECTIVES: To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). METHODS: Patients with RA. STUDY DESIGN: Prospective, 2-year follow-up. DATA COLLECTED: Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. ANALYSIS: Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. RESULTS: Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36-2.98) p<0.001 versus 1.61 (1.06-2.45) p=0.026 versus 1.75 (1.18-2.58) p=0.005 for the clinical versus US-GS versus US-PD evaluation, respectively. In the joints with normal baseline examination (clinical or US), an increased probability for structural progression in the presence of synovitis for the other modality was also observed (OR=2.16 (1.16-4.02) p=0.015 and 3.50 (1.77-6.95) p<0.001 for US-GS and US-PD and 2.79 (1.35-5.76) p=0.002) for clinical examination. Persistent (vs disappearance) synovitis after 4 months of therapy was also predictive of subsequent structural progression. CONCLUSIONS: This study confirms the validity of synovitis for predicting subsequent structural deterioration irrespective of the modality of examination of joints, but also suggests that both clinical and ultrasonographic examinations may be relevant to optimally evaluate the risk of subsequent structural deterioration.
22539487 The prevalence of clinical remission in RA patients treated with anti-TNF: results from th 2012 Sep OBJECTIVES: To evaluate the prevalence of clinical remission and minimal disease activity according to the ACR/European League Against Rheumatism (EULAR) remission, DAS-28 <2.6 and minimal disease activity (MDA) criteria, and to compare the extent of residual disease activity with disability in RA patients after 6 months of treatment with anti-TNF. METHODS: In the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic registry the prevalence of DAS-28 <2.6, MDA and ACR/EULAR remission criteria was assessed. Residual disease activity during MDA or remission was assessed as the percentage of patients with swollen and tender joints, elevated acute-phase reactants and general health on a visual analogue scale (VAS). Disability was evaluated with the HAQ score. RESULTS: Prevalence of DAS-28 <2.6 was 27%, prevalence of MDA was 34% and ACR/EULAR remission was reached by 6% of patients. Residual disease activity was present mostly in the most lenient criteria and occurred most frequently on the level of swollen joint count and VAS score: at least one swollen joint in DAS-28 <2.6, MDA and ACR/EULAR remission was present in, respectively, 51, 54 and 34% of the patients. VAS >1 occurred in, respectively, 67, 69 and 0% of the patients. Modification of the cut-point of the patient-reported outcome increased the prevalence of ACR/EULAR remission, but also the level of disability. CONCLUSION: MDA and DAS-28 <2.6 are reachable treatment targets in RA with anti-TNF, although residual disease activity might still be present. In turn, ACR/EULAR remission criteria leave little residual disease activity, but might be too stringent for use in daily clinical practice due to the strict cut-point in the patient-reported outcome.
22394488 Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citru 2012 Sep In the last years, the detection of antibodies (Abs) against citrullinated peptides (ACPA) has largely replaced rheumatoid factor (RF) as the most helpful biomarker in the diagnosis of rheumatoid arthritis (RA). Current assays detect ACPA reactivity with epitopes on various different citrullinated proteins. Among these, anti-cyclic citrullinated peptide (CCP) Abs have been widely demonstrated to be an important diagnostic and prognostic tool because of their high specificity. Recently, citrullinated vimentin, a protein highly released in synovial microenvironment, has been identified as potential autoantigen in the pathophysiology of RA and an enzyme-linked immunosorbent assay (ELISA) for the detection of Abs directed against a mutated citrullinated vimentin (anti-MCV) was developed. Several recent studies evaluating the characteristics of anti-MCV in comparison to anti-CCP Abs, have given conflicting results. Anti-MCV have been demonstrated to perform better than anti-CCP as predictor of radiographic damage. Conversely, its additional diagnostic and prognostic role in comparison to anti-CCP in both early and established RA is controversial. Aim of this study was to evaluate the diagnostic performance of anti-MCV in RA and to compare it to anti-CCP and the recently developed assay targeting viral citrullinated peptide 2 (VCP2) in a large cohort of RA patients (n=285), healthy subjects and other disease controls (n=227). Anti-MCV resulted to have a sensitivity of 59% and a specificity of 92%. In comparison, anti-CCP and anti-VCP2 displayed a sensitivity of 77% and 61% and a specificity of 96% and 95%, respectively. Of interest, at the manufacturer recommended cutoff value of 20U/mL, a high percentage of healthy subjects as well as Epstein Barr (EBV) and hepatitis C (HCV) virus infected patients resulted anti-MCV positive. In our large cohort of RA patients, anti-MCV demonstrated lower sensitivity than anti-CCP and VCP2 test, thus not allowing to confirm previously published data. Moreover, the high rate of detection in infectious diseases limits its diagnostic value in undifferentiated arthritis.
22983768 Evaluation of disease activity in rheumatoid arthritis by Routine Assessment of Patient In 2012 Dec Serial objective assessment of disease activity in rheumatoid arthritis (RA) is imperative to achieve remission. Routine Assessment of Patient Index Data 3 (RAPID3), an index without formal joint counts, appears attractive for evaluation of disease activity in RA patients in a busy clinical setting. This study aims to evaluate correlation and agreement of RAPID3 with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI) in RA patients. All patients completed a Multidimensional Health Assessment Questionnaire (MDHAQ) at each visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate were completed in 200 literate patients with RA to score DAS28, CDAI, and RAPID3. RAPID3 includes the three MDHAQ patient self-report RA core dataset measures for physical function, pain, and patient global estimate. Proposed RAPID3 (range, 0-30) severity categories of high (>12), moderate (6.1-12.0), low (3.1-6.0), and near remission (≤3) were compared to DAS28 (0-10) activity categories of high (> 5.1), moderate (3.21-5.1), low (2.61-3.2), and remission (≤ 2.6), and CDAI (0-76) categories of >22, 10.1-22.0, 2.9-10.0, and ≤2.8. Statistical significance was analyzed using Spearman correlations, cross-tabulations, and kappa statistics. Comparison of RAPID3 with DAS28 and CDAI indicated Spearman rank-order correlation coefficients for DAS28 with RAPID3 of 0.910, and for CDAI with RAPID3 of 0.907, all highly significant (P < 0.001). There was substantial agreement between RAPID3 and DAS28 (kappa value = 0.634, P < 0.001) and also between RAPID3 and CDAI (kappa value = 0.690, P < 0.001). Overall, 89-94 % of patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID severity criteria and 84-88 % who met DAS28 or CDAI remission/low activity criteria also met similar RAPID criteria. RAPID3 scores provide similar quantitative information to DAS28 and CDAI, and hence, is an informative index for evaluation of disease activity in RA in busy clinical settings.
21504991 Use of conservative and surgical foot care in an inception cohort of patients with rheumat 2011 Sep OBJECTIVES: To describe conservative and surgical foot care in patients with RA in England and explore factors that predict the type of foot care received. METHODS: Use of podiatry and type of foot surgery were outcomes recorded in an inception cohort involving nine rheumatology centres that recruited patients with RA between 1986 and 1998 across England. Associations between patient-specific factors and service use were identified using univariate logistic regression analyses. The independence of these associations was then verified through multiple binary logistic regression modelling. RESULTS: Data were collected on 1237 patients with RA [66.9% females, mean (s.d.) age at disease onset = 54.36 (14.18) years, median DAS = 4.09 (1st quartile = 3.04, 3rd quartile = 5.26), median HAQ = 1 (0.50, 1.63)]. Interventions involving the feet in the cohort were low with only 364 (30%) out of 1218 receiving podiatry and 47 (4%) out of 1237 patients having surgery. At baseline, female gender, increasing age at onset, being RF positive and higher DAS scores were each independently associated with increased odds of seeing a podiatrist. Gender, age of onset and baseline DAS were independently associated with the odds of having foot surgery. CONCLUSIONS: Despite the known high prevalence of foot pathologies in RA, only one-third of this cohort accessed podiatry. While older females were more likely to access podiatry care and younger patients surgery, the majority of the RA population did not access any foot care.
22776409 Associations between vitamin D, disease activity, and clinical response to therapy in rheu 2012 Sep OBJECTIVES: Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results. METHODS: Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go-Before Trial). Subjects were methotrexate and biologic therapy naïve. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response. RESULTS: Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (β-0.021 [95% CI -0.22, 0.18]), adjusted for age, race, sex, BMI, disease duration and glomerular filtration rate. Vitamin D deficiency was not associated with baseline vdHS scores or inflammatory markers in adjusted or unadjusted models. There was no association between baseline vitamin D deficiency and change in DAS28 (β = -0.024 [-0.30, 0.25]), proportion meeting ACR response (OR 0.82 [0.56, 1.20]), or radiographic progression at 52 weeks (OR 0.91 [0.59-1.40]). CONCLUSIONS: Vitamin D levels were not associated with RA disease activity, inflammatory markers, or vdHS scores at baseline. Furthermore, there was no association between baseline vitamin D level and response to therapy or radiographic progression.
20422194 Risk factors for development and progression of atlantoaxial subluxation in Korean patient 2011 Oct We sought to evaluate the frequency of cervical spine (C-spine) involvement, and associated risk factors for this disorder and its progression in Korean patients with rheumatoid arthritis (RA). From 1995 to 2008, we recruited patients with RA attending the rheumatology clinic of a single tertiary care hospital, and evaluated 1,120 of the patients who had neck pain for C-spine involvement. A diagnosis of C-spine involvement was made in 28.6% of patients evaluated, and within this group, anterior atlantoaxial subluxation (AAS) and subaxial subluxation were found in 89.7 and 15%, respectively. Of the 1,120 patients, 570 patients were followed for more than 3 years. Comparing the clinical characteristics of 193 patients with C-spine involvement and 377 patients without C-spine involvement, we found the associations with female gender, RA diagnosis at or before age 45, erosive changes in hand or foot radiographs, C-reactive protein levels and erythrocyte sedimentation rates at the time of first visit, and combination disease-modifying anti-rheumatic drug (DMARD) therapy. We found using logistic regression analysis that significant predictors of C-spine involvement included erosion in hand or foot radiographs (OR = 2.22, p = 0.001) and RA diagnosis at or before age 45 (OR = 2.26, p < 0.001). Among 137 patients followed for more than 3 years, for whom at least two consecutive X-rays were available, we observed radiographic progression in 60.4%. Patients with and without radiologic evidence for cervical progression did not differ significantly in clinical characteristics. In conclusion, Korean patients with RA frequently show radiographic evidence for progressive involvement of the cervical spine. Significant risk factors for C-spine involvement may be associated with erosive peripheral joint disease and RA diagnosis at an early age.
23077565 Analysis of the interferon gamma (rs2430561, +874T/A) functional gene variant in relation 2012 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients.
21572157 Time to treatment for new patients with rheumatoid arthritis in a major metropolitan city. 2011 Jul OBJECTIVE: To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists and treated with disease-modifying antirheumatic drugs (DMARD) within 3 months of symptom onset, to determine where treatment delays occur, and to identify contributing factors. METHODS: A retrospective cohort study in which adult patients with RA, diagnosed between January 1, 2003, and May 31, 2006, were recruited from rheumatologists' offices to participate in a telephone survey and chart review. The percentage treated with DMARD within 3 months of symptom onset was determined, along with median times for delay. Factors contributing to the delay were explored using multivariable logistic regression. RESULTS: Our study included 204 patients. Within 3 months of symptoms, 22.6% (95% CI 16.8%, 28.3%) received DMARD and within 6 months, 47.6% (95% CI 40.7%, 54.4%). The median time from symptom onset to DMARD was 6.4 months [interquartile range (IQR) 3.3, 12.0] with a median time from RA diagnosis by a rheumatologist to DMARD of 0.0 months (IQR 0.0, 1.0). Higher baseline swollen joint counts resulted in earlier treatment. Age, sex, education, comorbidity, rheumatologist practice type, and years since the physician's graduation did not affect time to treatment. CONCLUSION: Fewer than 25% of patients referred to rheumatologists were treated within 3 months of symptom onset. Identification of inflammatory arthritis and referral to rheumatologists are the key factors in timely care, because once patients are seen there is no delay to treatment. Future resources should be focused on development and evaluation of interventions to facilitate rapid triage, referral, and assessment by a rheumatologist.
21572146 Diagnostic accuracy of ACR/EULAR 2010 criteria for rheumatoid arthritis in a 2-year cohort 2011 Jul OBJECTIVE: To evaluate the diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and 1987 ACR criteria for rheumatoid arthritis (RA), and the respective role of the algorithm and scoring of the ACR/EULAR. METHODS: In total, 270 patients with recent-onset arthritis of < 1 year duration were included prospectively between 1995 and 1997 and followed for 2 years. RA was defined as the combination, at completion of followup, of RA diagnosed by an office-based rheumatologist and treatment with a disease-modifying antirheumatic drug or glucocorticoid. We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the criteria sets in the overall population, in the subgroup meeting the tree condition for ACR/EULAR scoring, and in the overall population classified according the full tree. RESULTS: At baseline, 111 of the 270 patients had better alternative diagnoses and 16 had erosions typical for RA; of the 143 remaining patients, 52 had more than 6 ACR/EULAR 2010 points (indicating definite RA) and 91 had fewer than 6 points. After 2 years, 11/16 patients with erosions and 40/52 with more than 6 points had RA. 100 of the 270 patients met the reference standard for RA. Sensitivity, specificity, PPV, and NPV of the ACR/EULAR (full tree) were 51/100 (51%), 153/170 (90%), 51/68 (75.4%), and 153/202 (75.7%), respectively. Diagnostic accuracies of the ACR/EULAR score and ACR 1987 criteria were not statistically different. CONCLUSION: Much of the improvement of the ACR/EULAR criteria was ascribable to the use of exclusion criteria in the algorithm.
21442165 Relationship between arterial dysfunction and extra-articular features in patients with rh 2012 Jun Systemic inflammation may be a common process that underpins both atherosclerosis and extra-articular features (ExRA) of rheumatoid arthritis (RA). We evaluated the relationship between ExRA and arterial dysfunction in 114 consecutive patients with RA (82% women) without overt arterial disease aged 40-65 years. A trained research nurse undertook 'SphygmoCor' pulse wave analysis (PWA) using radial applanation tonometry to measure the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWT, msec) of aortic wave reflection. Assessment included fasting blood sample, patient questionnaire and medical record review. Mean differences were adjusted for age, sex, mean blood pressure, smoking pack-years, fasting cholesterol, Stanford HAQ score and erythrocyte sedimentation rate. Mean age was 54 (SD 7) and median RA duration 10 (IQR 4-17) years. There was a trend for arterial dysfunction (higher AIX%; lower RWT) to increase as the number of ExRA features rose, but no difference in AIX% (-0.5, 95%CI -2.8 to 1.8, P = 0.65) or RWT (0.3 ms, 95%CI -3.6 to 4.2, P = 0.86) between 'any ExRA' and 'no ExRA'. Arterial dysfunction was not associated with the presence of rheumatoid nodules, Sjogren's syndrome or carpal tunnel syndrome. Our study was too small to determine whether severe ('Malmo') ExRA (vasculitis, pericarditis, episcleritis) was truly associated with a higher AIX% (3.8, 95%CI -2.3 to 9.9, P = 0.22) and lower RWT (-5.5 ms 95%CI -13.1 to 2.1, P = 0.16). While arterial dysfunction may be associated with the number of ExRA features and severe ExRA, it does not appear to be associated with other ExRA features.
22006120 Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-nega 2012 Aug We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.
22458503 New drug discovery strategies for rheumatoid arthritis: a niche for nonhuman primate model 2012 Apr INTRODUCTION: Despite the tremendous advances made in the treatment of rheumatoid arthritis (RA), there is still excess mortality observed in RA patients, which is mainly caused by cardiovascular disease (CVD). Altered lipid metabolism plays a major role in the etiology of CVD. A second common complication observed in RA patients is anemia. Both conditions are serious, reduce quality of life and are undertreated. AREAS COVERED: The authors postulate that there is a specific niche for nonhuman primate models of inflammatory arthritis to address these systemic complications that occur in RA. Furthermore, the authors postulate that these nonhuman primate models are a useful platform to unveil the mechanisms underlying dyslipidemia and anemia, which are responsible for the manifestation of these complications. EXPERT OPINION: The presence of currently untreated systemic complications of RA, such as dyslipidemia and anemia, provides interesting opportunities to include these in the preclinical evaluation of new therapies. In the selection of relevant models for the evaluation of new treatments for RA or the identification of new targets for therapy, we postulate that nonhuman primates should be considered as a valid preclinical model. Because of their closer immunological and physiological proximity to humans, these models in nonhuman primates can be valuable for studying disease-related aspects that cannot be addressed in rodent models.
22532638 Patient's global assessment of disease activity and patient's assessment of general health 2012 Dec OBJECTIVES: To assess (A) determinants of patient's global assessment of disease activity (PTGL) and patient's assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. METHODS: Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lin's coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. RESULTS: Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of -4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95-0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75-0.84) in RA activity state classification for all three indices. CONCLUSIONS: PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.
21213089 Rheumatoid synovectomy: does the surgical approach matter? 2011 Jul BACKGROUND: Surgical synovectomy relieves pain in patients with rheumatoid arthritis (RA). The comparative effect of arthroscopic versus open synovectomy on pain reduction, recurrence of synovitis, radiographic progression, and need for subsequent total joint arthroplasty (TJA) is unclear. Whether synovectomy relieves pain in patients with advanced degenerative joint changes is also controversial. QUESTIONS/PURPOSES: We therefore asked whether arthroscopic synovectomy resulted in equal pain relief, recurrence rates, rates of radiographic progression, likelihood of arthroplasty, and whether surgical synovectomy relieved pain and halted progression in the presence of advanced RA. METHODS: We searched PubMed, Cochrane Database of Systematic Reviews, and BMJ Clinical Evidence. After appropriate selection criteria, 58 studies were identified, including 36 on open synovectomy and 22 on arthroscopic synovectomy, with a total of 2589 patients and a mean followup of 6.1 years. Meta-analysis was performed for knees and elbows, comparing open versus arthroscopic synovectomy. Variables included the percentage of patients with pain reduction, recurrence of synovitis, radiographic progression, and need for subsequent TJA or arthrodesis. RESULTS: Patients undergoing arthroscopic synovectomy had similar pain reduction, but more frequent recurrences of synovitis and radiographic progression than patients with open synovectomy. Patients undergoing arthroscopic synovectomy had similar and decreased risks of subsequent elbow and knee arthroplasties, respectively. Advanced preoperative radiographic RA did not correlate with worse pain scores nor increased need for subsequent arthroplasty when compared with minimal degenerative joint changes. CONCLUSIONS: Arthroscopic synovectomy, while providing similar pain relief, may place patients at higher risk for recurrence and radiographic progression of RA. Advanced preoperative degenerative joint disease should not be an absolute contraindication to synovectomy. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
22462423 Randomized comparison of etanercept with usual therapy in an Asian population with active 2012 Apr AIM: Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia-Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia-Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia-Pacific countries. METHOD: In this open-label, active-comparator, parallel-design, multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR-N) area under the curve (AUC) over 16 weeks. RESULTS: Baseline characteristics were similar between groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference -145.3; P < 0.001). Significantly greater proportions of subjects achieved ACR 20, 50 and 70 responses with ETN + MTX versus DMARD + MTX at Week 16 (P < 0.05). Low Disease Activity Score based on a 28-joint count (DAS28 < 3.2) was also achieved by significantly more subjects in the ETN + MTX group versus the DMARD + MTX group (P < 0.001). Greater improvements were shown for DAS28, pain visual analogue scale, health assessment questionnaire, and physician and patient global assessments (P < 0.05) for ETN + MTX versus DMARD + MTX. No new safety signals were found. CONCLUSION: In this Asia-Pacific population of subjects with moderate to severe RA, ETN + MTX showed superior efficacy versus usual DMARD + MTX regimens, with similar safety profiles.