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ID PMID Title PublicationDate abstract
28845604 Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. 2017 Oct OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. METHODS: HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. RESULTS: Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95% CI 3.7-4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0-2.9) in Eastern Europe to 8.0 (95% CI 6.6-9.6) in Japan and 8.4 (95% CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. CONCLUSION: Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs.
28256445 Long-term changes in the quality of life of patients with rheumatoid arthritis treated wit 2018 Jul OBJECTIVE: To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. METHOD: Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. RESULTS: Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. CONCLUSIONS: In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment.
29146040 [Effectiveness, therapeutic maintenance and reasons for stopping tocilizumab (TCZ): A retr 2018 May OBJECTIVE: Study the therapeutic maintenance, efficacy and reasons for tocilizumab stop in daily practice. PATIENTS AND METHODS: A monocentric, retrospective study of patients treated for rheumatoid arthritis who received at least one TCZ infusion between January 2009 and December 2015. Therapeutic maintenance was evaluated using the Kaplan-Meier method. The efficacy of TCZ was measured by DAS28 and the EULAR response. Reasons for stopping and new treatment lines were also collected. RESULTS: Of the 88 patients (83% women and 17% men) who were included, the mean age was 54±12.5 years. There were 75% positive rheumatoid factors and 76% positive anti-CCP. The mean duration of the follow-up was 31 months. TCZ was used as monotherapy in 24 patients (27%). Before the introduction of TCZ, the mean DAS28 was 5.07±1.32. The EULAR response at 1 year in patients still under treatment (n=63) was obtained in 59 (93.7%) patients, 46 good responders and 13 moderate responders. Therapeutic maintenance was 82.9%, 72.5%, 68.7% and 57.2%, respectively, at 12, 24, 36 and 54 months. Twenty-eight patients (32%) followed TCZ, 10 for adverse events and 14 for ineffectiveness. Abatacept was the main new therapeutic line. CONCLUSION: The therapeutic maintenance of TCZ in common practice over a long period of follow-up is similar to pivotal studies. Efficacy data are reassuring in the long-term.
28748514 A systemic review and meta-analysis of the clinical efficacy and safety of total glucoside 2018 Jan To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.
28230269 Antigenic burden and serum IgG concentrations influence rituximab pharmacokinetics in rheu 2017 Aug AIMS: Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients. METHODS: In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. RESULTS: A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day(-1) , respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k(10) ) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10(-8) ), and that k(10) decreased with time (P = 0.00015), partly explained by a change in target-antigen amount. CONCLUSIONS: The association between CD19+ count and k(10) may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k(10) may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.
27775453 The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs 2017 May OBJECTIVES: To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). METHOD: Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. RESULTS: No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. CONCLUSIONS: Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.
28451869 Contribution of subjective Disease Activity Score 28 (DAS28) components to the response to 2017 Jun We investigated the contributions made by the subjective components of the Disease Activity Score 28 (DAS28) to the treatment response of rheumatoid arthritis (RA). In addition, factors associated with poor response to treatment at 6 months, despite normalization of objective measures, were examined. A total of 426 newly diagnosed RA patients were included. The DAS28-P score (the subjective components of the DAS28 relative to the total components) was calculated as DAS28-P = 0.56 ∗ sqrt(TJC28) + 0.014 ∗ (VAS-GH) /0.56 ∗ sqrt(TJC28) + 0.28 ∗ sqrt(SJC28) + 0.7 ∗ In(erythrocyte sedimentation rate (ESR)) + 0.014 ∗ (VAS-GH). The European League Against Rheumatism (EULAR) response was assessed after 6 months of treatment. Of those who failed to attain good EULAR responses, those for whom the objective measures (the ESR, the C-reactive protein level, and swollen joints) were normalized were defined as having failed treatment because of subjective measures. The median (IQR) DAS28 score at baseline was 4.8 (4.04-5.49) and that after 6 months of treatment 3.21 (2.41-3.95). The DAS28-P score fell significantly from baseline to 6 months in good (0.43 versus 0.28, p < 0.001) and moderate responders (0.44 versus 0.4, p = 0.003), but not in non-responders (0.43 versus 0.45, p = 0.727). Younger age, a lower DAS28 score, and a lower DAS28-P score at baseline were related to a good EULAR response. Subjects who failed to respond because of subjective measures tended to have higher DAS28-P scores at baseline. We found that RA patients with high DAS28-P scores, reflecting subjective measures, were less likely to achieve good EULAR responses 6 months after treatment initiation and tended not to be classified as good responders despite normalization of objective measures.
28196535 Factors associated with sexual dysfunction in Taiwanese females with rheumatoid arthritis. 2017 Feb 14 BACKGROUND: Patients with rheumatoid arthritis (RA) may experience sexual dysfunction because of symptoms or adverse effects from treatments. Data on female sexual dysfunction (FSD) in Asian females with RA issue are limited. This study investigated the prevalence and factors associated with FSD in Taiwanese patients with RA. METHODS: This cross-sectional study used a purposive sampling method to recruit 195 females with RA from a single hospital in southern Taiwan. Demographic and clinical characteristics were obtained by review of medical records and a structured questionnaire. The Chinese version of the Female Sexual Function Index and the Taiwanese Depression Questionnaire were also administered. Multiple logistic regression analysis was used to identify factors associated with FSD. RESULTS: The crude and age-standardized prevalence of FSD were 66.8% and 48.2%, respectively. Patients who were older, with a comorbid condition, with more depressive symptoms, and with greater disease activity had a significantly higher risk of FSD. CONCLUSION: Our findings indicate that FSD is more common in Taiwanese individuals with RA who have certain specific demographic and clinical characteristics. These findings may help to identify and facilitate the provision of appropriate interventions to ensure better sexual health in female patients with RA.
28663038 Measuring fatigue with multiple instruments in a Brazilian cohort of early rheumatoid arth 2017 Sep OBJECTIVE: To assess the prevalence of fatigue in a Brazilian population with early rheumatoid arthritis using multiple instruments, and the predictors of these instruments by differents independent variables. METHODS: Cross-sectional study with direct interview and medical records review. Fatigue, dependent variable, was assessed using eight instruments: Profile of Mood States (POMS), Multidimensional Assessment of Fatigue scale (MAF), Fatigue Severity Scale (FSS), Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), Numerical Rating Scales (BRAF-NRS), Short-form Survey 36 (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Visual Analogic Scale for Fatigue (VASf). INDEPENDENT VARIABLES: sociodemographic, clinical and serological, were measured using medical records and direct interview. Disability and disease activity were assessed using the Health Assessment Questionnaire (HAQ) and disease activity assessed using the Disease Activity Score 28 joints (DAS28). The scores of scales demonstrated the level of fatigue and multiple linear regression method used in statistical analysis to demonstrate prediction models. RESULTS: A total of 80 patients was assessed, and 57 reported clinically relevant fatigue (VASf>2), representing 71.25% prevalence point (51 women [89.5%], mean age 48.35±15 years, and mean disease duration of 4.92±3.8 years). Eight predictive models showed statistical significance, one for each fatigue instrument. The highest coefficient of determination (R(2)) was 56% for SF-36 and the lowest (R(2)=21%) for FSS. The HAQ was the only independent variable to predict fatigue on all instruments. CONCLUSION: Clinically relevant fatigue is a highly prevalent symptom and is mostly predicted by disability and age in the population assessed.
27886693 Gaps in Aging Research as it Applies to Rheumatologic Clinical Care. 2017 Feb The incidence and prevalence of rheumatologic conditions are increasing and the rheumatology workforce must be aware of aging-specific issues. This article reviews specific barriers to understanding the biology of aging and aging-related mechanisms that may underlie development of rheumatologic diseases in older adults. It summarizes gaps in the assessment, outcomes measurement, and treatment of these diseases in this unique population. It also highlights potential solutions to these barriers and suggests possible ways to bridge the gap, from a research and education standpoint, so that clinicians can be better prepared to effectively manage older adults with rheumatologic conditions.
27319613 Sleep disturbance in patients with rheumatoid arthritis is related to fatigue, disease act 2017 Mar OBJECTIVES: To explore factors related to sleep disturbance in patients with rheumatoid arthritis (RA). METHOD: Cross-sectional data from 986 patients in the Oslo RA Register (ORAR) collected in 2009 were included. Sleep problems were assessed by four measures: the Medical Outcomes Study (MOS) sleep disturbance scale, and the sleep components of the Rheumatoid Arthritis Impact of Disease (RAID) score, the Multi-Dimensional Health Assessment Questionnaire (MDHAQ), and the 15-dimensional quality of life questionnaire (15D). Patient-reported outcomes (PROs) were recorded using standard questionnaires for physical and mental function [the HAQ and the MOS 36-item Short-Form Health Survey (SF-36), disease activity (the RA Disease Activity Index, RADAI), utility (SF-6D), and visual analogue scales (VAS) for pain, fatigue, and disease activity]. Demographics including comorbidity were collected. Information on use of medication for RA and sleep disturbance was obtained using checklists. Multivariate analyses were used to identify factors independently associated with sleep problems by four different measures. RESULTS: The mean (standard deviation, SD) age of the patients was 59.4 (12.5) years, 76.9% were females, and the mean (SD) disease duration was 13.7 (10.7) years. The correlation between the various sleep measures was high (r(2) = 0.71-0.78). Sleep disturbance was moderately correlated to pain (r(2) = 0.41-0.61), fatigue (r(2) = 0.44-0.58), physical function (r(2) = 0.33-0.48), RADAI (r(2) = 0.42-0.55), and utility (r(2) = 0.49-0.61). RAID sleep demonstrated the highest correlation with other PROs. RADAI, fatigue, the mental component score of SF-36, physical function, body mass index (BMI), and use of Z-drugs/benzodiazepines were independently associated with two or more measures of sleep problems (all p < 0.001). CONCLUSIONS: Sleep disturbance measured by four different measures was independently related to other PROs including fatigue, pain, and disease activity in RA patients.
27032755 Value of body mass index in the diagnosis of obesity according to DEXA in well-controlled 2017 Jan BACKGROUND: Rheumatoid arthritis (RA) has an indirect effect on body composition. Body mass index (BMI) is not a valid predictor of body fat in RA patients. OBJECTIVE: To evaluate the accuracy of BMI in identifying obesity diagnosed according to dual energy X-ray absorptiometry (DXA) in well-controlled RA patients. METHODS: An observational, cross-sectional, descriptive, analytical study. We used 3 different cutoffs for obesity as determined by DXA: >35% total fat, >40% total fat, and >35% central fat mass (central obesity). RESULTS: One hundred one patients were included. We found that 35% total fat corresponded to a BMI of 24kg/m(2), with a sensitivity of 90% and specificity of 75% (area under the curve [AUC] 0.917); 40% total fat to a BMI of 25kg/m(2), with a sensitivity of 86% and specificity of 39% (AUC 0.822); and 35% central fat mass to a BMI of 22kg/m(2), with a sensitivity of 97% and specificity of 84% (AUC 0.951). CONCLUSION: Obesity according to DXA was underdiagnosed when the classic BMI cutoffs were used in well-controlled RA patients.
28258078 Short-term low-magnesium diet reduces autoimmune arthritis severity and synovial tissue ge 2017 Apr 1 Magnesium has been suggested to have anti-inflammatory properties in short-term, mostly in vitro studies. To examine the effect of dietary magnesium modifications in arthritis severity and joint damage DA rats were placed on one of three diet regimens before the induction of autoimmune pristane-induced arthritis (PIA): a 4 wk low-magnesium diet, normal diet, and a magnesium-supplemented diet. The diets were switched to a normal diet 14 days after the induction of PIA (typical time of disease onset). Arthritis severity was scored for 38 days, and joints were examined by histology and quantitative PCR for proinflammatory genes. Rats on the low-magnesium diet were significantly and reproducibly protected and had 70% lower median arthritis severity score, with preservation of normal joint histology without erosive changes. Rats on the normal or magnesium-supplemented diets were not protected and developed equally severe and erosive disease. While the dietary modifications were at disease onset (day 14 postinduction), the protective effect of the short-term low-magnesium diet persisted, suggesting a lasting effect on a critical pathogenic pathway. Rats on the low-magnesium diet had significant reduction in synovial tissue expression of IL-6, RORA, and RORC, which are genes required for the development of Th17 T cells. This study revealed a novel role for dietary magnesium in the regulation of autoimmune arthritis and opens new possibilities for the treatment of autoimmune diseases such as rheumatoid arthritis and psoriatic arthritis with short courses of dietary or drug-induced modulations of magnesium levels.
28057522 Nanomedicines for dysfunctional macrophage-associated diseases. 2017 Feb 10 Macrophages play vital functions in host inflammatory reaction, tissue repair, homeostasis and immunity. Dysfunctional macrophages have significant pathophysiological impacts on diseases such as cancer, inflammatory diseases (rheumatoid arthritis and inflammatory bowel disease), metabolic diseases (atherosclerosis, diabetes and obesity) and major infections like human immunodeficiency virus infection. In view of this common etiology in these diseases, targeting the recruitment, activation and regulation of dysfunctional macrophages represents a promising therapeutic strategy. With the advancement of nanotechnology, development of nanomedicines to efficiently target dysfunctional macrophages can strengthen the effectiveness of therapeutics and improve clinical outcomes. This review discusses the specific roles of dysfunctional macrophages in various diseases and summarizes the latest advances in nanomedicine-based therapeutics and theranostics for treating diseases associated with dysfunctional macrophages.
28693070 [Expression of annexin A1 in peripheral blood cells of Naïve rheumatoid arthritis patient 2017 Jul 4 Objective: To explore the expression of Annexin a1 (AnxA1) mRNA in peripheral blood mononuclear cells (PBMC) from Naïve rheumatoid arthritis (RA) patients and healthy controls and to investigate its influencing factors. Methods: Thirty Naïve RA patients and 36 healthy controls were recruited from the First Affiliated Hospital of Harbin Medical University between May 2013 and January 2015.All RA patients were fulfilled the classification criteria of ACR in 1987.Clinical characteristics and laboratory indexes were collected.Real time polymerase chain reaction (RT-PCR) was used to measure AnxA1 and Foxp3 mRNA expression respectively.Serum TNF-α, IL-17 and IL-10 levels in each group was determined separately by enzyme linked immunosorbent assay (ELISA). Furthermore, correlations between the expression of AnxA1 mRNA and clinical characteristics, laboratory parameters, Foxp3 mRNA, serum IL-17, TNF-α, IL-10 level in Naïve RA patients were analyzed. Results: The expressions of AnxA1 mRNA in PBMC of Naïve RA patients were lower than that of healthy controls [0.12 (0.05-0.30) versus 1.66 (0.40-2.68), P<0.05]. The Foxp3 mRNA expressions in PBMC of Naïve RA patients were also lower than that of healthy controls [0.77 (0.39-1.89) versus 2.93 (2.65-3.49), P<0.05], while serum TNF-α, IL-17, and IL-10 levels of Naïve RA patients were higher than those of healthy controls (P<0.05). The expression of AnxA1 was positively associated with the expression of Foxp3 mRNA (r(s)=0.513, P<0.05) and negatively associated with the serum IL-17 level (r(s)=-0.381, P<0.05). But there were no correlations between expression of AnxA1 in PBMCs from Naïve RA patients with the TNF-α, IL-10 level, clinical characteristics (sex, age, disease duration and disease activity) and the laboratory indexes (RF, Anti-CCP antibody, ESR and CRP). The expression of Foxp3 mRNA and the serum IL-17 level was the independent influencing factor. Conclusions: The reduced expression of AnxA1 may associate with the reduced expression of Foxp3 and the increased IL-17 level in Naïve RA patients.It suggested that AnxA1 may play a key role in immune regulation and anti-inflammatory process in the pathogenesis of RA.
28249848 Systematic review of the methodological quality of controlled trials evaluating Chinese he 2017 Mar 1 OBJECTIVES: We appraised the methodological and reporting quality of randomised controlled clinical trials (RCTs) evaluating the efficacy and safety of Chinese herbal medicine (CHM) in patients with rheumatoid arthritis (RA). DESIGN: For this systematic review, electronic databases were searched from inception until June 2015. The search was limited to humans and non-case report studies, but was not limited by language, year of publication or type of publication. Two independent reviewers selected RCTs, evaluating CHM in RA (herbals and decoctions). Descriptive statistics were used to report on risk of bias and their adherence to reporting standards. Multivariable logistic regression analysis was performed to determine study characteristics associated with high or unclear risk of bias. RESULTS: Out of 2342 unique citations, we selected 119 RCTs including 18 919 patients: 10 108 patients received CHM alone and 6550 received one of 11 treatment combinations. A high risk of bias was observed across all domains: 21% had a high risk for selection bias (11% from sequence generation and 30% from allocation concealment), 85% for performance bias, 89% for detection bias, 4% for attrition bias and 40% for reporting bias. In multivariable analysis, fewer authors were associated with selection bias (allocation concealment), performance bias and attrition bias, and earlier year of publication and funding source not reported or disclosed were associated with selection bias (sequence generation). Studies published in non-English language were associated with reporting bias. Poor adherence to recommended reporting standards (<60% of the studies not providing sufficient information) was observed in 11 of the 23 sections evaluated. LIMITATIONS: Study quality and data extraction were performed by one reviewer and cross-checked by a second reviewer. Translation to English was performed by one reviewer in 85% of the included studies. CONCLUSIONS: Studies evaluating CHM often fail to meet expected methodological criteria, and high-quality evidence is lacking.
28296767 Fractal analysis of subchondral bone changes of the hand in rheumatoid arthritis. 2017 Mar Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder. Conventional radiography, a widely available and cost-effective examination method, remains the standard of reference for the detection and quantification of joint involvement in RA. Fractal dimension (FD) of the trabecular bone structure has been proven to correlate with the bone's physical properties. The present study was designed to use fractal analysis to validate radiograph changes in the hand of RA patients.This study retrospectively evaluated the hand radiographs of 108 subjects. Fifty-four patients were suffering from RA, of which 18 were men and 36 were women. Their ages ranged from 25 to 90 years. The hand radiographs of 54 healthy patients, 18 men and 36 women (age range 23-88 years), were used as the control group. Bone structure value (BSV) is a critical parameter for the assessment and analysis of bone microarchitecture. The BSVs were calculated over the fractal dimension using the Brownian motion.The BSV calculated for ROI showed a significant difference in ROI5 (0.210 ± 0.045), ROI6 (0.186 ± 0.066), and ROI11 (0.201 ± 0.056) in patients with RA, in comparison to the CG (P < 0.05). A significant correlation was observed between anti-CCP and ROI4, ROI5, ROI6, ROI9, and ROI12 in seropositive RA patients (post hoc test (Bonferroni) P <0.001).This study demonstrates that the bone textural image analysis technique can be used to quantify the radiographic changes in RA hands, based on comparisons of FDs.
28865493 High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with 2017 Sep 2 BACKGROUND: Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. METHODS: Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. RESULTS: Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. CONCLUSIONS: RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA. Baseline RF/anti-CCP titers may serve as indices that aid infliximab treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00691028 . Retrospectively registered on 3 June 2008.
28978340 Ultrasound of the hand is sufficient to detect subclinical inflammation in rheumatoid arth 2017 Oct 4 BACKGROUND: Ultrasound (US) is a sensitive method for detecting joint/tendon inflammation in patients with rheumatoid arthritis (RA). Subclinical inflammation is often found in patients with RA in composite score remission. The purpose of the present study was to explore whether US of only the hands is sufficient to identify subclinical inflammation in patients with established RA in clinical remission. METHODS: A total of 209 patients with established RA (81% women, mean [SD] age 53.3 (13.2) years, disease duration 10.0 [8.8] years) were examined when initiating biologic disease-modifying anti-rheumatic drugs (bDMARDs) and after 6 months (184 patients) and 12 months (152 patients) of follow-up. They were assessed by US (greyscale [GS] and power Doppler [PD] of 36 joints and 4 tendons, scored 0-3) as well as clinical and laboratory examinations, and different disease activity composite scores were calculated. The presence of US synovitis (GS score ≥ 2, PD score ≥ 1 [PD1] and score ≥ 2 [PD2]) in composite score remission was explored. RESULTS: Remission at 6 and 12 months was achieved in 74 and 59 patients, respectively, for Disease Activity Score based on 28 joints (DAS28); in 37 and 38 patients, respectively, for Clinical Disease Activity Index; in 42 and 42 patients, respectively, for Simplified Disease Activity Index; and in 38 and 35 patients, respectively, for Boolean remission. The percentages of patients in DAS28 remission at 6 months with synovitis in hands/other regions were 73.0%/64.9% for GS, 64.9%/41.9% for PD1 and 32.4%/20.3% for PD2; at 12 months, the corresponding percentages were 61.0%/64.4% for GS, 62.7%/39.0% for PD1 and 44.1%/15.3% for PD2, respectively. PD activity was more often present in the hands (p < 0.001). In patients in various composite scores of remission, US only of the hands identified ≥ 90% of the patients having PD activity in any of the assessed joints/tendons. CONCLUSIONS: A high percentage of patients had US synovitis despite being in clinical remission. US examination performed only of the hands captured ≥ 90% of patients with subclinical inflammation and could be feasible for assessing bDMARD-treated patients with RA in remission. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12610000284066 . Registered on 8 April 2010.
28165538 Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patien 2017 Jun 1 OBJECTIVE: To clarify the characteristics of lymphoproliferative disorder (LPD) in patients with RA treated with MTX. METHODS: Among 33 patients developing LPD during MTX treatment, 20 LPDs regressed spontaneously within 12 weeks after MTX cessation (regressive LPD), and 13 did not regress and most of them died or needed chemotherapy (persistent LPD). The control group consisted of 66 clinically matched MTX-treated RA patients without LPD. The clinical characteristics were compared between these three groups. RESULTS: While no significant differences were found in clinical RA and LPD features among the three groups, the absolute lymphocyte number of the two LPD groups at LPD diagnosis was significantly lower than the control group (497/µl in the regressive vs 680/µl in the persistent vs 1400/µl in the control, P < 0.05). After MTX withdrawal, the lymphocyte number in the regressive group rapidly recovered to 1214/µl (P < 0.01) by week 2 and was thereafter maintained at an equivalent level to the control group. In contrast, lymphocyte level in the persistent group did not show significant increase throughout 12 weeks (620/µl at week 2, P = 0.57). Changes in lymphocyte number following MTX withdrawal clearly distinguished the regressive LPD from the persistent LPD. CONCLUSION: A significant decrease in lymphocyte count at the LPD diagnosis and its restoration after MTX withdrawal were markedly associated with spontaneous regression of LPD developing during MTX treatment.