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ID PMID Title PublicationDate abstract
23077978 The choice of adjuvant determines the cytokine profile of T cells in proteoglycan-induced 2013 Jan Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation of the synovial joints. Collagen-induced arthritis (CIA) and proteoglycan-induced arthritis (PGIA) are mouse models of inflammatory arthritis; CIA is a T helper type 17 (Th17) -dependent disease that is induced with antigen in complete Freund's adjuvant, whereas PGIA is Th1-mediated and is induced using antigen in dimethyldioctadecyl-ammonium bromide (DDA) as an adjuvant. To investigate whether the type of adjuvant determines the cytokine profile of the pathogenic T cells, we have compared the effect of CFA and DDA on T-cell responses in a single arthritis model. No differences in incidence or disease severity between aggrecan-T-cell receptor transgenic mice immunized with aggrecan in either CFA or DDA were observed. Immunization with CFA resulted in a higher proportion of Th17 cells, whereas DDA induced more Th1 cells. However, the levels of interleukin-17 (IL-17) produced by T cells isolated from CFA-immunized mice after antigen-specific stimulation were not significantly different from those found in DDA-immunized mice, indicating that the increased proportion of Th17 cells did not result in significantly higher ex vivo IL-17 levels. Hence, the choice of adjuvant can affect the overall proportions of Th1 and Th17 cells, without necessarily affecting the level of cytokine production or disease incidence and severity.
25530330 Late-onset rheumatoid arthritis in the Counties Manukau District Health Board region of Ne 2014 Dec 19 AIM: The aim of this retrospective study was to investigate whether there are differences in the early treatment of Rheumatoid Arthritis (RA) depending on the age of the patient at diagnosis. METHODS: The electronic records of 127 newly diagnosed RA patients presenting to the Counties Manukau District Health Board Rheumatology outpatient clinic between January 2008 and December 2010 were reviewed. Demographics, disease severity, relevant investigations, and medication use were analysed using Pearson's Chi squared test, Fisher's exact test and t-test. RESULTS: The cohort included 32 aged greater than or equal to 60 years with Late Onset RA (LORA) and 95 aged <60 years with Young Onset RA (YORA). No significant differences in baseline disease severity, disease modifying anti-rheumatic drug or prednisone use rates were observed between the LORA and YORA groups, with methotrexate use rates of 26/32 (81.25%) and 74/95 (77.89%) respectively. Nonsteroidal anti-inflammatory (NSAID) rate was significantly lower (p=0.013) in the LORA group 14/32 (43.75%) compared to the YORA group 65/95 (68.42%), reflecting an awareness of the adverse effects of these drugs in an older population. CONCLUSION: Patients with new onset rheumatoid arthritis at our institution received similar disease modifying anti-rheumatic drug treatment irrespective of their age.
24129133 Use of data from multiple registries in studying biologic discontinuation: challenges and 2013 Jul Many studies have been conducted concerning discontinuation of biologic disease-modifying anti-rheumatic drugs (DMARD), but mainly in trial settings which result in limited generalisability. Registry studies can complement the current literature of biologic DMARD discontinuation by providing more generalisable information. However, it may be necessary to combine registries to increase power and provide more diverse patient populations. This increased power could provide us information about risk and benefits of discontinuing biologic DMARD in typical clinical practice. However, use of multiple registries is not without challenges. In this review, we discuss the challenges to combining data across multiple registries, focusing on biologic discontinuation as an example. Challenges include: 1) generalizability of each registry; 2) new versus prevalent users designs; 3) outcome definitions; 4) different health care systems; 5) different follow up intervals; and 6) data harmonisation. The first three apply to each registry, and the last three apply to combining multiple registries. This review describes these challenges, corresponding solutions, and potential future opportunities.
23789454 [Perception of pain in rheumatoid arthritis: relation to inflammation, psychic disorders, 2013 Pain perception was analyzed depending on the inflammatory activity of rheumatoid arthritis (RA), variants and manifestations of psychic disorders (including depressive, anxious and moderate cognitive ones), chronic fatigue, changes in the functional status and quality of life. The study included 125 patients (mean age 47.4 +/- 1.01 yr) with definitive diagnosis of RA 138.4 +/- 10.1 months in duration. RA activity was estimated from the DAS28 index, pain intensity and degree of fatigue by BPI and FSS scales respectively, the functional status and life quality by HAQ and EQ-5D. Psychic disorders were diagnosed by a psychiatrist in accordance with ICD-10 with the use of relevant psychiatric and psychological scales and methods. Pain perception was unrelated to the patients' age and RA duration. The multifactor analysis provided a basis for the prognostic model suggesting that the most severe pain in RA is related to the functional status and quality of life (VAS of general health status), hsCRP level, inflammatory activity index RA DAS28, peripheral platelet count, degree of fatigue (FSS) and depression (YADS), female sex. Depression and its severity is one more factor influencing pain perception in RA and accounting for functional insufficiency and low quality of life. Early diagnostics of psychic disorders (in the first place anxious and depressive ones) is mandatory to ensure effective combined therapy of pain in RA patients.
23955067 Cell-signaling therapy in rheumatoid arthritis. 2013 Oct New treatments for rheumatoid arthritis (RA) continue to emerge to meet unsatisfied needs of a significant number of patients. The development of new, oral biologic therapy is a significant step forward, although these drugs will require further evaluation in clinical settings before their true potential is appreciated. This new, oral biologic therapy has mostly focused on inhibition of intracellular signaling. These mechanisms and the available studies regarding the efficacy and safety of specific drugs which interfere with these mechanisms are the subject of this article.
22674870 Association between body mass index and anti-citrullinated protein antibody-positive and a 2013 Jan OBJECTIVE: Being overweight or obese is associated with many chronic diseases, but previous studies of the association with rheumatoid arthritis (RA) have shown inconsistent results. The aim of this study was to investigate the association between body mass index (BMI) and the risk of developing the 2 main subtypes of RA. METHODS: At inclusion, cases and controls answered questions about their weight and height and donated blood samples. The presence of antibodies to citrullinated protein antigens (ACPAs) was analyzed among 2,748 cases and 3,444 controls (28% men). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression. RESULTS: Compared to those with normal weight (BMI <25 kg/m(2) ), the adjusted overall OR for developing ACPA-negative RA was 1.1 (95% CI 0.9-1.3) for overweight individuals (BMI ≥25 to <30 kg/m(2) ) and 1.4 (95% CI 1.1-1.9) for obese individuals (BMI ≥30 kg/m(2) ). When stratified by sex, the OR for ACPA-negative RA for obese women was 1.6 (95% CI 1.2-2.2), and there was no association between obesity and ACPA-negative RA in men (OR 1.1, 95% CI 0.6-1.8). In obese men compared to men with normal weight, the OR for ACPA-positive RA was 0.6 (95% CI 0.3-0.9), while there was no association between BMI and ACPA-positive RA among women (OR 1.0, 95% CI 0.8-1.2). CONCLUSION: Our findings show that obesity is associated with developing ACPA-negative RA in women, and indicate an inverse association between BMI and ACPA-positive RA in men.
25267563 Occurrence of pulmonary rheumatoid nodules following biological therapies. 2015 Sep In rheumatoid arthritis (RA), disease activity is generally determined by the joint involvement, but the treatment outcome is often influenced by extra-articular manifestations. Authors present a 74-year-old female patient's case history, who was treated with seropositive RA. Marked disease activity was observed even following combined traditional disease-modifying antirheumatic drug (DMARD) treatment (disease activity score in 28 joints (DAS28) = 6.6). Therefore, the patient received TNF-α antagonist therapy. Golimumab was administered subcutaneous (SC) once monthly which resulted in significant improvement in both clinical and laboratory signs (DAS28 = 3:43). However, the follow-up chest x-ray indicated multiple intrapulmonary foci and enlarged lymph nodes. Biopsies and histology excluded malignancy; rheumatoid nodules were confirmed. Anti-TNF therapy was discontinued and tocilizumab treatment was initiated. The IL-6 receptor inhibitor suppressed arthritic activity, and 2 months later, the follow-up chest x-ray showed a regression of chest nodules. Our cases, as well as reports from other centers, suggest that TNF blockade may induce rheumatoid nodulosis and the use of alternative biologics may be feasible as further treatment of RA.
24068385 Assessment of global disease activity in RA patients monitored in the METEOR database: the 2014 Apr The objectives of this study were to compare the patient's (PtGDA) and physician's (PhGDA) assessment of global disease activity and to identify factors that might influence these differences as well as factors that may influence the patient's and the physician's scores separately. Anonymous data were used from 2,117 Dutch patients included in the Measurement of efficacy of Treatment in the Era of Rheumatology database. PtGDA and PhGDA were scored independently on a 100-mm visual analog scale (VAS) with 0 and 100 as extremes. The agreement, intraclass correlation coefficients (ICC), was calculated and a Bland-Altman plot was created to visualize the differences between PtGDA and PhGDA. Linear mixed model analysis was used to model PtGDA and PhGDA. Logistic repeated measurements were used to model the difference in PtGDA and PhGDA (PtGDA > PhGDA versus PtGDA ≤ PhGDA). Gender patient, gender physician, age, swollen joint count (SJC), tender joint count, VAS pain, disease duration, and erythrocyte sedimentation rate (ESR) were considered as possible determinants in both models. Mean (standard deviation) age was 57 (15) years and 67 % of the patients were female. Agreement between PtGDA and PhGDA was moderate (ICC, 0.57). Patients scored on average 11 units higher (worse) than rheumatologists (95 % limits of agreement, -25.2 to 47.6). Patient's perception of pain (VAS) was positively associated with a PtGDA being higher than PhGDA. Similarly, ESR and swollen joint counts were positively associated with a PtGDA being lower or equal to the PhGDA. Patients rate global disease activity consistently higher than their rheumatologists. Patients base their judgment primarily on the level of pain, physicians on the level of SJC and ESR.
23554320 Impact of etanercept on work and activity impairment in employed moderate to severe rheuma 2013 Oct OBJECTIVE: To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA). METHODS: This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test. RESULTS: RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001). CONCLUSION: In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment.
25294026 Ten-year incidences of self-reported non-vertebral fractures in Japanese patients with rhe 2015 Mar Despite improvements in rheumatoid arthritis disease activity of in the past 10 years, the incidence of self-reported non-vertebral fractures did not decrease in our cohort of 9,987 patients. This study may indicate that osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the rheumatoid arthritis disease activity. INTRODUCTION: Although rheumatoid arthritis (RA) is a risk factor for osteoporosis and fractures, few studies have described the association between disease activity and the fracture incidence in patients with RA. This study aimed to investigate changes in the non-vertebral fracture incidence between 2001 and 2010 in our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. METHODS: The IORRA is a prospective observational cohort study of Japanese RA patients. A total of 9,987 patients with RA were enrolled in this cohort from 2000 to 2010. The clinical parameter and non-vertebral fracture occurrence data were collected biannually through self-reported questionnaires. Incidences of self-reported non-vertebral fractures were also analyzed via standardization according to gender, age, and disease activity during each 2-year period. RESULTS: From 2001 to 2010, the percentage of patients with 28-joint disease activity score remission increased from 7.8 to 39.7%, prednisolone intake decreased from 51.4 to 41.3%, and bisphosphonate intake increased from 5.0 to 23.4%. The non-vertebral fracture incidence rates were 24.6/1,000 person-years in 2001 and 35.5/1,000 person-years in 2010, with no apparent change even after standardization. The overall non-vertebral fracture incidence was significantly higher in the autumn/winter than in the spring/summer (p = 0.02). CONCLUSION: Despite improvements in disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in our patients with RA. Osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the disease control in patients with RA.
24760193 HLA-DRB1 frequency in patients with familial and sporadic rheumatoid arthritis in north ea 2014 Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that has a strong correlation with HLA-DRB1. Family history is considered a known risk factor for RA. The aims of this study were to compare the frequency of HLA-DRB1 alleles between patients with sporadic and familial RA and also between healthy controls with RA patients (sporadic and familial) and clarify if familial RA is more severe than sporadic RA. This study included 129 consecutive patients with sporadic and 48 cases with familial (first-degree siblings) RA who visited a rheumatology unit. Demographic data, including extra-articular involvement, mean disease activity according to DAS28 (ESR) criteria, and main laboratory findings, were compared between patients with sporadic and familial RA. HLA-DRB1 typing was carried out using the PCR-SSP method, and the frequency of each allele was determined in all cases and compared with the results of HLA-DRB1 frequencies in 72 healthy controls who were previously reported by our group in northeast Iran. Patients with sporadic and familial RA were matched in age and sex, most of the cases in both groups were females. The mean age of patients was 45 years. Ocular involvement was the most frequent extra-articular manifestation of our patients. There was no significant difference between the two groups in visual analogue scale (VAS) index, number of inflamed or tender joints, extra-articular involvements, and main laboratory findings. HLA-DRB1* 01 (55 %), 04 (48 %), and 03 (43 %) alleles were the most frequent alleles in both sporadic and familial diseases. The frequency of HLA-DRB1*11 and HLA-DRB1*13 was significantly higher in normal participants compared with RA (p = 0.001). There was no significant difference in the HLA-DRB1 allele's frequency between sporadic and familial RA. Therefore, familial aggregation was not associated with RA severity.
23436821 Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheu 2013 Aug OBJECTIVE: Treat-to-target (T2T) leads to improved clinical outcomes in early rheumatoid arthritis (RA). The question is whether these results sustain in the long term. Our objective was to investigate the 3-year results of a protocolized T2T strategy in daily clinical practice. METHODS: In the Dutch Rheumatoid Arthritis Monitoring remission induction cohort, patients newly diagnosed with RA were treated according to a T2T strategy aimed at remission (Disease Activity Score in 28 joints [DAS28] <2.6). Patients were treated with methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with anti-tumor necrosis factor α agents in case of failure. Primary outcomes were disease activity, Health Assessment Questionnaire (HAQ) score, Short Form 36 physical component summary (PCS) and mental component summary (MCS) scores, and the Sharp/van der Heijde score (SHS) after 3 years. Secondary outcomes were sustained DAS28 remission (≥6 months) and remission according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition. RESULTS: After 3 years (n = 342), 61.7% of patients were in DAS28 remission and 25.3% met the provisional ACR/EULAR definition of remission. Sustained remission was experienced by 70.5%, which in the majority was achieved with conventional disease-modifying antirheumatic drugs only. The median scores were 0.4 (interquartile range [IQR] 0.0-1.0) for the HAQ, 45.0 (IQR 38.4-53.2) for the PCS, 53.1 (IQR 43.2-60.8) for the MCS, and 6.0 (IQR 3.0-13.0) for the total SHS. CONCLUSION: In very early RA, T2T leads to high (sustained) remission rates, improved physical function and health-related quality of life, and limited radiographic damage after 3 years in daily clinical practice.
25403368 Lack of association of matrix metalloproteinase-3 gene polymorphism with susceptibility to 2014 Nov 18 BACKGROUND: Epidemiological studies have investigated the association between matrix metalloproteinase-3(MMP-3) gene-1171 5A/6A polymorphism and rheumatoid arthritis (RA), but the results were inconsistent. To evaluate the specific relationship, we performed a meta-analysis to clarify the controversies. METHODS: The relevant literatures dated to December 07th 2013 were retrieved from PubMed, EMBASE and the China National knowledge Infrastructure (CNKI) databases. The number of the alleles and genotypes for MMP-3 were obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP-3 5A/6A promoter polymorphism and RA. All of the statistical analyses were conducted by STATA11.0 software. RESULTS: A total of 6 case-control studies covering 1451 cases and 1239 controls were included in the final meta-analysis. There was no significant association between MMP-3 5A/6A promoter polymorphism and RA in all genetic models (for 6A versus 5A: OR=1.19, 95% CI=0.91-1.56, P=0.203; 5A/6A versus 5A/5A: OR=1.31, 95% CI=0.89-1.92, P=0.174; 6A/6A versus 5A/5A: OR=1.78, 95% CI=0.68-4.61, P=0.238; the recessive model: OR=1.48, 95% CI=0.88-2.47, P=0.141; and the dominant model: OR=1.46, 95% CI=0.71-3.00, P=0.299). In the subgroup analysis by ethnicity, we obtained the similar results. CONCLUSIONS: We systematically investigate the association between MMP-3-1171 5A/6A polymorphism and RA susceptibility; however, the results show a lack of correlation. Considering the small sample size and the selection bias existed in some studies, further studies are needed to confirm the findings.
24223608 The -174G/C and -572G/C interleukin 6 promoter gene polymorphisms in mexican patients with 2013 OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 -174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 -174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and -572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.
23339423 From desk to bed: computational simulations provide indication for rheumatoid arthritis cl 2013 Jan 22 BACKGROUND: Rheumatoid arthritis (RA) is among the most common human systemic autoimmune diseases, affecting approximately 1% of the population worldwide. To date, there is no cure for the disease and current treatments show undesirable side effects. As the disease affects a growing number of individuals, and during their working age, the gathering of all information able to improve therapies--by understanding their and the disease mechanisms of action--represents an important area of research, benefiting not only patients but also societies. In this direction, network analysis methods have been used in previous work to further our understanding of this complex disease, leading to the identification of CRKL as a potential drug target for treatment of RA. Here, we use computational methods to expand on this work, testing the hypothesis in silico. RESULTS: Analysis of the CRKL network--available at http://www.picb.ac.cn/ClinicalGenomicNTW/software.html--allows for investigation of the potential effect of perturbing genes of interest. Within the group of genes that are significantly affected by simulated perturbation of CRKL, we are lead to further investigate the importance of PXN. Our results allow us to (1) refine the hypothesis on CRKL as a novel drug target (2) indicate potential causes of side effects in on-going trials and (3) importantly, provide recommendations with impact on on-going clinical studies. CONCLUSIONS: Based on a virtual network that collects and connects a large number of the molecules known to be involved in a disease, one can simulate the effects of controlling molecules, allowing for the observation of how this affects the rest of the network. This is important to mimic the effect of a drug, but also to be aware of -and possibly control- its side effects. Using this approach in RA research we have been able to contribute to the field by suggesting molecules to be targeted in new therapies and more importantly, to warrant efficacy, to hypothesise novel recommendations on existing drugs currently under test.
24056521 Predictors of response and remission in a large cohort of rheumatoid arthritis patients tr 2014 Jan OBJECTIVE: The objective of this study was to identify predictors of response and remission to tocilizumab (TCZ) in RA patients seen in daily routine clinical practice. METHODS: The efficacy of TCZ was evaluated after 12 and 24 weeks of treatment by the European League Against Rheumatism (EULAR) response criteria. Regression analysis was performed to study the association between remission or EULAR response and the following characteristics: gender, age, current smokers, prior cardiovascular disease (CVD), 28-joint disease activity score (DAS28), CRP, RF or ACPA positivity, combination therapy with DMARDs and TCZ as the first biological therapy or after failure of at least one biological therapy. RESULTS: In total, 204 patients were included with a mean DAS28 score of 5.14. EULAR response and remission were obtained in 86.1% and 40% of patients, respectively, at week 24. In multiple regression analysis, a high baseline CRP level [odds ratio (OR) 4.454 (95% CI 1.446, 13.726)] was significantly associated with EULAR response at week 24 and, inversely, age >55 years [OR 0.285 (95% CI 0.086, 0.950)] and prior CVD [OR 0.305 (95% CI 0.113, 0.825)] were significantly associated with lower EULAR response at week 24. Older age was also associated with less remission at week 24 [OR 0.948 (95% CI 0.920, 0.978)]. No additional effectiveness was found when TCZ was used in combination with a DMARD or when patients were naive to biological agents. CONCLUSION: In daily practice we identified three predictors of a better response for TCZ therapy in RA: a younger age, a high baseline CRP level and no history of CVD.
24334643 Flares in rheumatoid arthritis: frequency and management. A report from the BRASS registry 2014 Feb OBJECTIVE: To describe the frequency, duration, and management of flares as reported by patients with rheumatoid arthritis (RA). METHODS: Data were collected in a prospective observational study of patients with RA recruited from a single academic center and treated according to the rheumatologists' discretion. Every 6 months, patients reported the number and duration of RA flares and described how these were managed in terms of adding or changing medication and use of nonpharmacologic strategies. RESULTS: Of patients who reported flares at least once during the study, 74% reported having flares 6 months prior to study entry and 59% reported flares prior to the first 6-month visit. At subsequent visits, 54-57% reported having > 1 flare. Thirty percent of patients in remission reported flares. Flare duration lasted ≥ 2 weeks in 30%, 1-2 weeks in 13%, and < 1 week in 57%. Forty percent reported medication changes at the time of their flare; 16% changed medication and used nonpharmacologic strategies and 26% of patients reported no changes in treatment as a result of flares. Longer duration of flare was associated with changes in disease-modifying therapy. CONCLUSION: Patients with RA experienced flares more often when noted to be in higher disease activity states than when in remission and reported changes in disease-modifying antirheumatic drugs or biologics more frequently when flares were of longer duration. There is a need to prospectively study symptom intensity and duration of flare in relation to disease activity and consider self-management strategies in the development of a measure of flare.
25295917 Usefulness of MR imaging of the parotid glands in patients with secondary Sjögren's syndr 2015 May OBJECTIVE: To assess the correlation between MR imaging (MRI) of parotid glands with X-ray sialography, histopathology of the labial salivary glands, and salivary secretion, in patients with secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). METHODS: Non-contrast MRI of the parotid glands was performed in 13 secondary SS patients associated with RA who satisfied the revised Japanese diagnostic criteria for SS (1999), and the ACR/EULAR classification criteria for RA (2010). The MRI findings were classified according to the degree of high-intensity signal on T1-weighted images (T1WI) and short inversion time inversion recovery (STIR) images into five grades (0-4), using the modified Nagasaki University grading method. The results of MRI grading were compared with the Rubin and Holt staging of X-ray sialography (0-4), the Greenspan grading of labial salivary gland histopathology (0-4), and salivary secretion by the gum test (ml/10 min). RESULTS: All 13 patients were females, with a mean age of 50.2 ± 11.3 years. According to the MRI grading, 3 patients were Grade 1, 5 were Grade 2, 5 were Grade 3, and none was Grade 0 or Grade 4. The mean stage by X-ray sialography was 1.7 ± 1.0, the mean grade by histopathology was 2.4 ± 1.2, and the mean volume of salivary secretion was 9.7 ± 3.9 ml. The MRI grading correlated significantly with the Rubin and Holt staging and Greenspan grading (P < 0.01 each, Spearman's rank correlation), and significantly and inversely with the results of the gum test (P < 0.05). CONCLUSION: The results suggest that MRI of the parotid glands is a useful noninvasive tool for evaluating destruction and inflammation in the salivary glands.
24390938 Whole-body MRI assessment of disease activity and structural damage in rheumatoid arthriti 2014 May OBJECTIVE: The aim of this study was to investigate the ability of whole-body MRI (WBMRI) to visualize inflammation [synovitis, bone marrow oedema (BME) and enthesitis] and structural damage in patients with RA. METHODS: The 3T WBMR images were acquired in a head-to-toe scan in 20 patients with RA and at least one swollen or tender joint. Short Tau Inversion Recovery and pre- and post-contrast T1-weighted images were evaluated for readability and the presence/absence of inflammation (synovitis, BME and enthesitis) and structural damage (erosions and fat infiltrations) in 76 peripheral joints, 30 entheseal sites and in the spine. RESULTS: The readability was >70% for all individual joints, except for the most peripheral joints of the hands and feet. Synovitis was most frequent in the wrist, first tarsometatarsal, first CMC joints and glenohumeral joints (67-61%); BME in the wrist, CMC, acromioclavicular and glenohumeral joints (45-35%) and erosions in the wrist, MTP and CMC joints (19-16%). Enthesitis at ≥ 1 site was registered in 16 patients. BME was frequently seen in the cervical (20%) but not the thoracic and lumbar spine, while fat infiltrations and erosions were rare. The intrareader agreement was high (85-100%) for all pathologies. The agreement between WBMRI and clinical findings was low. CONCLUSION: Peripheral and axial inflammation and structural damage at joints and entheses was frequently identified by WBMRI, and more frequently than by clinical examination. WBMRI is a promising tool for evaluation of the total inflammatory load of inflammation (an MRI joint count) and structural damage in RA patients.
22972745 Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying antirheuma 2013 Mar OBJECTIVE: To assess the safety and tolerability of tocilizumab (TCZ) as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe rheumatoid arthritis (RA) who had an inadequate response at study entry to their current treatment with biologic agents or DMARDs. METHODS: This 24-week, multicenter, open-label, phase IIIb study conducted in the US enrolled 886 patients. Treatments were allocated to patients based on their current therapy at study entry. Patients receiving monotherapy with biologic agents were assigned to TCZ 8 mg/kg monotherapy. All other patients were randomized to either TCZ 4 mg/kg + DMARDs or TCZ 8 mg/kg + DMARDs. The primary end point was the number and percentage of patients with serious adverse events (SAEs) during 24 weeks of TCZ treatment. Efficacy assessments were evaluated as secondary outcomes. Data were analyzed descriptively. RESULTS: Overall, 69 patients (7.8%) reported ≥1 SAEs. The rate of SAEs per 100 person-years was 28.3 (95% confidence interval [95% CI] 23.1-34.4) overall and was similar across treatment groups: 29.1 (95% CI 21.0-39.2), 30.3 (95% CI 22.2-40.2), and 20.6 (95% CI 10.3-36.9) in the TCZ 4/8 mg/kg + DMARDs, TCZ 8 mg/kg + DMARDs, and TCZ 8 mg/kg monotherapy groups, respectively. The most common SAEs were infections (i.e., pneumonia [1.0%] and cellulitis [0.9%]). In addition, American College of Rheumatology response rates and reductions in mean Disease Activity Score based on a 28-joint count were generally similar among treatment groups. CONCLUSION: The safety findings in this study were consistent with the previously identified safety profile of TCZ. TCZ had an AE profile consistent with prior randomized blinded studies and was effective when administered as either monotherapy or in combination with DMARDs for the treatment of RA.