Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
34995761 Methotrexate in early rheumatoid arthritis: Is the anchor drug still holding? 2022 Apr Treat-to-target (T2T) is currently the most fashionable strategy for treatment-naïve, early rheumatoid arthritis (RA) patients. A T2T approach can lead to a complete and drug-free disease remission, whereas failure to obtain remission leads to damage early in the disease course. Hence, one should try to achieve high remission rates as early as possible, implementing the best therapeutic strategies available. Methotrexate (MTX) combined with glucocorticoid bridging is the mainstay of T2T. However, MTX is often used suboptimally in RA patients for many reasons, including poor tolerability, low compliance, and safety issues. Recent evidence has suggested that novel targeted synthetic DMARDs (tsDMARDs) such as the Janus-kinase (JAK) inhibitors in combination with glucocorticoids yielded better outcomes in early RA than conventional treatment. Such an approach may have advantages in terms of patients' outcomes, though some concerns about serious adverse events need to be addressed.
35462089 The Structural Index Score and its relation to foot function, disability and physical perf 2022 May OBJECTIVES: To evaluate the Structural Index Score (SIS) - a clinical foot deformity assessment index developed for RA, and to compare its results with foot function, disability and physical performance tests. METHODS: In this cross-sectional study, 104 patients with foot pain were evaluated according to SIS score, subscales (Forefoot SIS and Rearfoot SIS) and items. Results were compared with the Foot Function Index (FFI), the Health Assessment Questionnaire Disability Index (using lower limbs items: LL-HAQ), and physical performance tests: Berg Balance Scale (BBS), the Timed Up and Go test (TUG) and the 5-Time Sit down-to-Stand up Test (SST5). RESULTS: There was a weak correlation of SIS score with FFI and LL-HAQ. Rearfoot SIS was correlated with FFI, LL-HAQ and worse performance in BBS, TUG and SST5. Regarding Rearfoot SIS items, the ankle ROM was correlated to all studied outcomes, the calcaneus varus/valgus was correlated with FFI (total, pain and disability subscales) and the planus/cavus deformity with FFI-pain, HAQ-DI and LL-HAQ. Forefoot SIS did not correlate with any outcome measures. In relation to Forefoot SIS items, hallux valgus was associated with foot function (FFI-total, pain and disability subscales), the MTPs joints subluxation was correlated with FFI-disability subscale, and the 5th MTP exostosis was associated with FFI-pain. CONCLUSION: SIS score was correlated to impaired foot function (FFI) and disability (LL-HAQ). Rearfoot SIS was correlated to worse performance on FFI, LL-HAQ, BBS, TUG and SST5. SIS score index can be a useful tool to evaluate the rheumatoid foot deformities, but a better graduation of foot deformities should add sensitivity to this method.
34718869 Temperature might increase the hospital admission risk for rheumatoid arthritis patients i 2022 Jan Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0-11 (RR = 2.68, 95% CI: 1.23-5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03-1.91) and 1.24 (95% CI: 1.0-1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01-1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02-2.15) and lag 0-2 (RR = 2.35, 95% CI: 1.11-4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission.
35200118 User experience with a voice-enabled smartphone app to collect patient-reported outcomes i 2022 May OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease, requiring frequent patient-provider interaction and self-monitoring. We developed a novel mobile health smartphone app with a voice-enabled feature to help patients virtually track disease activity and ask general questions about RA. METHODS: With a user-centered design (UCD) approach, we developed a voice-enabled app (VEA) which was then tested in two focus groups of patients (n=8) and one with providers (n=4). Voice enablement and a question and answer (Q & A) library function were previously requested by patients. Based on focus group feedback, the VEA was refined and tested with 26 patients for 56 days. The VEA asked patients to fill in daily patient-reported outcomes (PROs) and complete the trial with a satisfaction survey. RESULTS: Of the 26 patients in the VEA trial, 77% were female and 50% were aged 55 and older. Adherence to daily PROs during the 56-day trial was 66%, with <1% of PROs completed using the voice-enabled feature. PROMIS short forms and RADAI-5 PROs remained stable. Of the 22 satisfaction survey respondents, 86% were satisfied with their overall experience with the app and 18.5% were satisfied with voice enablement. The voice assistant had an 86% success rate at understanding and answering interactions regarding surveys and a 44% success rate regarding Q & A interactions. CONCLUSIONS: We developed a novel VEA through a UCD framework and conducted pilot testing. Adherence was moderate and RADAI-5 and PROMIS measures were stable. Based on satisfaction results, PROs may not be the best use of voice enablement technology.
35587067 The effect of statin on major adverse cardiovascular events and mortality in patients with 2022 May OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the effect of statin on major adverse cardiovascular events (MACE) and mortality in patients with RA. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, Scopus, Embase, and Clinicaltrials.gov for studies investigating the effect of statin on MACE and mortality in RA patients up until 6 February 2022. The primary outcome was MACE, which can be defined as nonfatal myocardial infarction (MI), nonfatal presumed ischemic stroke, transient ischemic attack, any coronary or non-coronary revascularization, or cardiovascular death. The pooled effect estimated was reported as hazard ratio (HR). RESULTS: There were 40,307 patients from a total of six studies, comprising of one double-blind placebo controlled randomized controlled trial, four propensity-score matched cohorts, and one observational study included in this meta-analysis. The rate of MACE was lower in RA patients receiving statin [OR 0.67 (95%CI 0.51, 0.89), p=0.005; I2: 21.0%, p=0.29] (Figure 2). Sensitivity analysis using fixed-effect model showed that MACE was lower in the statin group [OR 0.73 (95%CI 0.62, 0.87), p<0.0051 I2: 21.0%, p=0.29]. Mortality was lower in RA patients receiving statin [OR 0.73 (95%CI 0.62, 0.88), p<0.001; I2: 29.0%, p=0.25] (Figure 3). Sensitivity analysis using fixed-effect model showed that mortality was lower in the statin group [OR 0.75 (95%CI 0.66, 0.85), p<0.001 I2: 29.0%, p=0.25]. CONCLUSIONS: This systematic review and meta-analysis showed that statin was associated with reduction of MACE and mortality in patients with RA.
32829446 Data Mining Study on Prescription Patterns of Different Dosage Forms of Chinese Herbal Med 2022 Mar OBJECTIVE: To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices. METHODS: Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups. RESULTS: (1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions. CONCLUSIONS: The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.
32524889 Changes in hand grip strength and body weight after a dynamic exercise program and Mediter 2022 Apr BACKGROUND: In patients with rheumatoid arthritis (RA) exercise improves muscle strength and decreases fat mass, whereas the consumption of a Mediterranean diet (MD) also has been associated with higher grip strength. Therefore, it is important to explore the combined effects of these interventions on hand grip strength and weight in RA. OBJECTIVE: To determine the combined effect of an MD and a dynamic exercise program (DEP) on hand grip strength in women with RA. METHOD: In a randomized clinical trial, 106 women with RA were included and assigned to the DEP-MD, DEP and MD groups. Weight, body circumferences, Disease Activity Score-28, Health Assessment Questionnaire Disability Index [HAQ-DI], and hand grip strength were measured at baseline and 24 weeks after the interventions. RESULTS: After 24 weeks, hand grip strength showed a significant increase in the DEP group (median 2 kg) compared with DEP-MD (median 0.5 kg) and MD (median -0.5 kg) groups (p = 0.03). In the MD group weight and waist circumference showed a significant decrease (-2.2 kg and -4.3 cm) compared with DEP-MD (0.85 kg and 1.9 cm) and DEP (0.35 kg and 0.5 cm) groups (p < 0.01). Finally, a significant decrease was observed in the HAQ-DI after treatment in the DEP-MD group of -0.5 and the DEP group of -0.25 compared with the MD group with no change (p = 0.03). CONCLUSION: In women with RA, in addition to pharmacological treatment, DEP increases hand grip strength and an MD decreases weight and waist circumferences, while the combination of DEP and MD improves disability.
35063223 Validity of bioimpedance for assessment of fat-free mass in women with Rheumatoid Arthriti 2022 Feb BACKGROUND & AIMS: The aim was to assess the validity of bioimpedance in the assessment of fat free mass (FFM) among women and to study if the validity differs between women with and without Rheumatoid Arthritis (RA). METHODS: 38 women with RA and 24 non-rheumatic controls were included. FFM was measured in the non-fasting state using DXA (Lunar Prodigy), multi-frequency bioelectrical impedance analysis (BIA) (MF-BIA [Tanita MC-180 MA]), single-frequency BIA (SF-BIA) and bioelectrical impedance spectroscopy (BIS) (both Impedimed SFB7). BIS raw data were also used to calculate FFM from equations by Matthie, Jaffrin and Moissl. Results were compared using correlation, Bland Altman analysis, Mann Whitney U test and Wilcoxon Signed Ranks Test. RESULTS: Women with RA had different body water distribution compared to women without RA (p < 0.05). Median bias in FFM assessed by bioimpedance was 0.62-7.87 kg with wide limits of agreement for all methods. Median FFM differed significantly from DXA by all bioimpedance methods except for BIS by Jaffrin. Women with RA had significantly smaller biases compared to non-rheumatic controls using BIS equations by Matthie (p = 0.012) and Moissl (p = 0.025). Correlations between FFM measured by DXA and bioimpedance (r = 0.73-0.85, all p < 0.001) did not differ between groups. The sensitivity of bioimpedance to detect low fat free mass index (FFMI) was 0-47%. CONCLUSION: The results of this study show that bioimpedance has similar validity in women with RA compared to non-rheumatic controls, despite differences in body water distribution. Agreement with DXA improved when applying specific equations, but the clinical utility of bioimpedance is questionable as all methods failed to identify low FFMI with acceptable precision. TRIAL REGISTER: Clinicaltrials.org, NCT04247009.
35038176 A deep learning classification of metacarpophalangeal joints synovial proliferation in rhe 2022 Feb OBJECTIVE: To evaluate if an automatic classification of rheumatoid arthritis (RA) metacarpophalangeal joint conditions in ultrasound images is feasible by deep learning (DL) method, to provide a more objective, automated, and fast way of RA diagnosis in clinical setting. MATERIALS AND METHODS: DenseNet-based DL model was used and both training and testing are implemented in TensorFlow 1.13.1 with Keras DL libraries. The area under curve (AUC), accuracy, sensitivity, and specificity values with 95% CIs were reported. The statistical analysis was performed by using scikit-learn libraries in Python 3.7. RESULTS: A total of 1337 RA ultrasound images were acquired from 208 patients, the number of images is 313, 657, 178, and 189 in OESS Grade L0, L1, L2, and L3, respectively. In Classification Scenario 1 SP-no versus SP-yes, three experiments with region of interest of size 192 × 448 (Group 1), 96 × 224 (Group 2), and 96 × 224 stacked with pre-segmented annotated mask of SP area (Group 3) as input achieve an AUC of 0.863 (95% CI: 0.809, 0.917), 0.861 (95% CI: 0.805, 0.916), and 0.886 (95% CI: 0.836, 0.936), respectively. In Classification Scenario 2 Healthy versus Diseased, experiments in Group 1, Group 2 and Group 3 achieve an AUC of 0.848 (95% CI: 0.799, 0.896), 0.864 (95% CI: 0.819, 0.909), and 0.916 (95% CI: 0.883, 0.952), respectively. CONCLUSION: We combined DenseNet model with ultrasound images for RA condition assessment. The feasibility of using DL to create an automatic RA condition classification system was also demonstrated. The proposed method can be an alternative to the initial screening of RA patients.
34462262 Joint inflammation tends to recur in the same joints during the rheumatoid arthritis disea 2022 Feb OBJECTIVES: We investigated whether local joint swelling recurs in the same joints over time in patients with rheumatoid arthritis (RA) who are treated to target. METHODS: Patients with newly diagnosed RA participating in the Behandel-Strategieën, "treatment strategies" (BeSt) study (n=508) were followed for median 10 years while receiving Disease Activity Score (DAS) ≤2.4 steered treatment. Every 3 months 68 joints were assessed for the presence of swelling. We evaluated whether baseline local joint swelling was predictive for swelling in the same joint during follow-up using a multilevel mixed-effect logistic regression model. Different strategies were used to account for missing data. A permutation test was performed to assess if joint swelling was better predicted by baseline swelling of the joint itself than by baseline swelling of randomly selected other joints. RESULTS: In 46% of the joints that were swollen at baseline, joint swelling later recurred at least once during follow-up. Joint swelling at baseline was statistically significantly associated with swelling in the same joint during follow-up (OR 2.37, 95% CI 2.30 to 2.43, p<0.001), and also specifically with recurrent swelling in the same joint (OR 1.73, 95% CI 1.37 to 1.59, p<0.001). Local joint swelling was better predicted by baseline swelling of that particular joint than by baseline swelling of other joints (p<0.001). CONCLUSION: Joint swelling tends to recur locally in the joints swollen at RA onset. This suggests that local factors influence the manifestation of joint inflammation over time.
34774696 Transdermal release of methotrexate by cationic starch/poly(vinyl alcohol)-based films as 2022 Jan 5 Methotrexate (MTX) is a common drug used for rheumatoid arthritis (RA) treatment; however, a series of adverse effects associated with its oral or subcutaneous administration is reported. Transdermal delivery of MTX is an alternative to abate these issues, and the use of drug delivery systems (DDS) based on polymeric films presents an impressive potential for this finality. Based on this, in this study, we report the preparation of films made by cationic starch (CSt), poly(vinyl alcohol) (PVA), and chondroitin sulfate (ChS) to incorporate and release MTX, as well as the in vivo evaluation in model of rheumatoid arthritis in mice. CSt/PVA and CSt/PVA/ChS-based films (with and without MTX) were prepared using a simple protocol under mild conditions. The films loaded with 5 w/w-% of MTX exhibited appreciable drug loading efficiency and distribution. The MTX permeation through the layers of porcine skin demonstrated that most of the drug permeated was detected in the medium, suggesting that the formulation can provide a systemic absorption of the MTX. In vivo studies performed in an arthritis-induced model in mice demonstrated that the MTX-loaded films were able to treat and attenuate the symptoms and the biochemical alterations related to RA (inflammatory process, oxidative stress, and nociceptive behaviors). Besides, the pharmacological activity of MTX transdermally delivery by the CSt/PVA and CSt/PVA/ChS films was comparable to the MTX orally administered. Based on these results, it can be inferred that both films are prominent materials for incorporation and transdermal delivery of MTX in a practical and non-invasive manner.
34915341 Omega 3 polyunsaturated fatty acids: Potential anti-inflammatory effect in a model of ovar 2022 Feb OBJECTIVE: To evaluate the effect of polyunsaturated fatty acid-type omega 3 (ω3) on the temporomandibular joint (TMJ) of ovariectomized rats (OVX) with rheumatoid arthritis (RA). DESIGN: Rheumatoid arthritis was induced using complete Freund's adjuvant and type II bovine collagen injected at the base of the tail. Twenty-four adult female rats were treated by gavage and divided into four groups: G1: Sham, treated with 0.9% NaCl; G2: OVX, treated with 0.9% NaCl; G3: OVX+RA treated with 0.9% NaCl; G4: OVX+RA+ω3 treated with omega 3 (300 mg/kg/day). The induction of rheumatoid arthritis in groups G3 and G4 was performed 21 days after OVX, treatments were started 15 days after the induction of rheumatoid arthritis, maintained for 7 days, and killed. Bilateral TMJs were removed and assigned to morphometric analysis by micro-computed tomography and immunoassay to assess levels of cytokines IL-1β, IL-6, TNF-α, and IL-10. RESULTS: Higher levels of inflammatory cytokines were found in the G2 and G3 (P < 0.05) and anti-inflammatory cytokines in the G1 and G4. TMJ analysis by micro-computed tomography showed a higher percentage of bone volume (median - interquartile deviation) in G1 (96.2-1.1) than in the G2 (91.5-2.0, P = 0.0374) and G3 (85.1-5.2, P = 0.0001) but showed no statistically significant differences with the G4 (93.1-1.7, P = 0.79). CONCLUSIONS: Omega 3 successfully reduced TMJ damage in rats caused by ovariectomy and induced rheumatoid arthritis, and is a promising alternative for bone repair and attenuation of inflammatory processes.
34142326 Towards Personalising the Use of Biologics in Rheumatoid Arthritis: A Discrete Choice Expe 2022 Jan INTRODUCTION: There have been promising developments in technologies and associated algorithm-based prescribing ('stratified approach') to target biologics to sub-groups of people with rheumatoid arthritis (RA). The acceptability of using an algorithm-guided approach in practice is likely to depend on various factors. OBJECTIVE: This study quantified preferences for an algorithm-guided approach to prescribing biologics (termed 'biologic calculator'). METHODS: An online discrete choice experiment (DCE) was designed to elicit preferences from patients and the public for using a 'biologic calculator' compared with conventional prescribing. Treatment approaches were described by five attributes: delay to starting treatment; positive and negative predictive value (PPV/NPV); risk of infection; and cost saving to the UK national health service. Each survey contained six choice sets asking respondents to select their preferred option from two hypothetical biologic calculators or conventional prescribing. Background questions included sociodemographics, health status and healthcare experiences. DCE data were analysed using mixed logit models. RESULTS: Completed choice data were collected from 292 respondents (151 patients with RA and 142 members of the public). PPV, NPV and risk of infection were the most highly valued attributes to respondents deciding between prescribing strategies. CONCLUSION: Respondents were generally receptive to personalised medicine in RA, but researchers developing personalised approaches should pay close attention to generating evidence on both the PPV and the NPV of their technologies.
35078443 Effect of ambient temperature on outpatient admission for osteoarthritis and rheumatoid ar 2022 Jan 25 BACKGROUND: Current findings on the impact of weather conditions on osteoarthritis (OA) and rheumatoid arthritis (RA) are sparse and not conclusive. This study aimed to investigate the relationship between temperature change and OA/RA admission. METHODS: Daily OA/RA admission, meteorological data and pollutants from 1 January 2014 to 31 December 2017 in Hefei, China, were collected. We quantified the relationship between ambient temperature and OA/RA admission using a distributed lag nonlinear model (DLNM). Stratified analyses by gender and age were also examined. RESULTS: Temperature decrease was significantly associated with RA admission (25th percentile of temperature versus 50th percentile of temperature), with the acute and largest effect at current days lag (RR: 1.057, 95%CI: 1.005-1.111). However, no significant association between temperature and OA admission was observed. When conducting subgroup analyses by individual characteristics, we found that females and patients aged 41-65 years were more vulnerable to temperature decrease than males, patients aged 0-40 and ≧66 years, respectively. CONCLUSIONS: This study suggested that temperature decrease was a risk factor for increases in RA admission. Females and patients aged 41-65 years were particularly vulnerable to the effect of temperature decrease.
35394510 Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries Wi 2022 Apr 1 IMPORTANCE: Cytokine signaling, including tumor necrosis factor (TNF) and interleukin (IL)-6, through the Janus-kinase (JAK)-signal transducer and activator of transcription pathway, was hypothesized to attenuate the risk of Alzheimer disease and related dementia (ADRD) in the Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative based on multiomics phenotyping. OBJECTIVE: To evaluate the association between treatment with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept and risk of incident ADRD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among US Medicare fee-for-service patients with rheumatoid arthritis aged 65 years and older from 2007 to 2017. Patients were categorized into 3 cohorts based on initiation of tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors compared with a common comparator abatacept (a T-cell activation inhibitor). Analyses were conducted from August 2020 to August 2021. MAIN OUTCOMES AND MEASURES: The main outcome was onset of ADRD based on diagnosis codes evaluated in 4 alternative analysis schemes: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Hazard ratios (HRs) with 95% CIs were calculated from Cox proportional hazard regression after adjustment for 79 preexposure characteristics through propensity score matching. RESULTS: After 1:1 propensity score matching to patients using abatacept, a total of 22 569 propensity score-matched patient pairs, including 4224 tofacitinib pairs (mean [SD] age 72.19 [5.65] years; 6945 [82.2%] women), 6369 tocilizumab pairs (mean [SD] age 72.01 [5.46] years; 10 105 [79.4%] women), and 11 976 TNF inhibitor pairs (mean [SD] age 72.67 [5.91] years; 19 710 [82.3%] women), were assessed. Incidence rates of ADRD varied from 2 to 18 per 1000 person-years across analyses schemes. There were no statistically significant associations of ADRD with tofacitinib (analysis 1: HR, 0.90 [95% CI, 0.55-1.51]; analysis 2: HR, 0.78 [95% CI, 0.53-1.13]; analysis 3: HR, 1.29 [95% CI, 0.72-2.33]; analysis 4: HR, 0.50 [95% CI, 0.21-1.20]), tocilizumab (analysis 1: HR, 0.82 [95% CI, 0.55-1.21]; analysis 2: HR, 1.05 [95% CI, 0.81-1.35]; analysis 3: HR, 1.21 [95% CI, 0.75-1.96]; analysis 4: HR, 0.78 [95% CI, 0.44-1.39]), or TNF inhibitors (analysis 1: HR, 0.93 [95% CI, 0.72-1.20]; analysis 2: HR, 1.02 [95% CI, 0.86-1.20]; analysis 3: HR, 1.13 [95% CI, 0.86-1.48]; analysis 4: 0.90 [95% CI, 0.60-1.37]) compared with abatacept. Results from prespecified subgroup analysis by age, sex, and baseline cardiovascular disease were consistent except in patients with cardiovascular disease, for whom there was a potentially lower risk of ADRD with TNF inhibitors vs abatacept, but only in analyses 2 and 4 (analysis 1: HR, 0.76 [95% CI, 0.50-1.16]; analysis 2: HR, 0.74 [95% CI, 0.56-0.99]; analysis 3: HR, 1.03 [95% CI, 0.65-1.61]; analysis 4: HR, 0.45 [95% CI, 0.21-0.98]). CONCLUSIONS AND RELEVANCE: This cohort study did not find any association of risk of ADRD in patients treated with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept.
34752939 Estimates of minimal clinically important improvments vary with the responsiveness of the 2022 Feb OBJECTIVE: Minimal clinically important improvements (MCII) are known to vary with the baseline level in the sample. We examined if MCIIs are also larger in samples with higher responsiveness. STUDY DESIGN AND SETTING: In a prospective longitudinal study of patients with active rheumatoid arthritis, we assessed arthritis activity before and after new treatments. We estimated anchor-based MCIIs for three outcomes (pain severity, physical functioning by the Health Assessment Questionnaire, and Simplified Disease Activity Index, a composite measure) using receiver operating characteristic curves. We compared MCIIs among patients treated with three interventions of different impact (dose escalation, new disease-modifying medication, or prednisone). Separately, we used simulations to estimate MCIIs in five groups of responsiveness. RESULTS: Among 250 patients, standardized response means (SRMs) increased across the dose escalation, disease-modifying treatment, and prednisone treatment groups (-0.74, -1.00, and -1.53, respectively). MCIIs were also highest in the prednisone group. For example, corresponding MCIIs were -5.5, -8.9, and -13.8 for the composite measure. In the simulations, MCIIs (range -4.6 to -11.9) varied directly with SRMs (range -0.40 to -1.33). Results were similar for pain and the Health Assessment Questionnaire. CONCLUSION: The MCII is not an intrinsic measurement property but varies directly with sample responsiveness.
35526074 Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease acti 2022 May 7 BACKGROUND: Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source. METHODS: The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses. RESULTS: We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day). CONCLUSION: PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis. TRIAL REGISTRATION: The protocol was registered at PROSPERO ( CRD42021253685 ).
35357358 The effectiveness and safety of Simiao Xiaobi decoction on rheumatoid arthritis: A study p 2022 Mar 25 BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disease that contributes to progressive disability, systemic complications, higher mortality, and societal burden. Typical symptoms of RA include symmetrical pain and swelling in multiple joints, morning stiffness, and elevated levels of erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor. The representative treatment for RA is medication, including disease-modifying antirheumatic drugs, glucocorticoids, and nonsteroidal anti-inflammatory drugs. However, these medications are not yet curative nor preventative and are associated with several adverse effects, leading to their discontinuation. Recent articles reported that Simiao Xiaobi decoction (SXD) could relieve the symptoms of RA by clinical trial and experimental study, but an evidence-based review on the effectiveness and safety of SXD on RA has not yet been provided. METHODS: Searching for randomized controlled trials on the use of SXD for RA will be performed by using multiple electronic databases, manual search, and contacting the authors by e-mail if needed. Studies will be selected according to the predefined criteria and the data collected on study participants, interventions, control groups, outcome measurements, their results, adverse events, and risk of bias will be summarized. The primary outcome will be the disease activity score (including effective rate, swollen joint count, tender joint count, and morning stiffness), and the secondary outcomes will be blood tests (including erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. We will use Review Manager software to perform a meta-analysis, the Cochrane Collaboration "risk of bias" tool for assessing the risk of bias, and grades of recommendation, assessment, development and evaluation for the determination of the quality of evidence. TRIAL REGISTRATION NUMBER: https://inplasy.com; INPLASY202230026. RESULTS: We are going to investigate the effectiveness and safety of SXD for RA. CONCLUSION: This study will provide reliable evidence on whether SXD is effective on RA.
33651342 Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Cr 2022 Apr • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects. • Further studies in the field are needed to support such association We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)-regarding RA risk in subjects exposed to FCS-yelled to an overall OR of 1.94 (95% CI 1.46-2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35-2.25 and OR 1.23, 95% CI 1.06-1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40-4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.
34817776 A molecular insight of inflammatory cascades in rheumatoid arthritis and anti-arthritic po 2022 Mar Rheumatoid arthritis (RA) is an auto-immune inflammatory disorder of the synovial lining of joints marked by immune cells infiltration and hyperplasia of synovial fibroblasts which results in articular cartilage destruction and bone erosion. The current review will provide comprehensive information and results obtained from the recent research on the phytochemicals which were found to have potential anti-arthritic activity along with the molecular pathway that were targeted to control RA progression. In this review, we have summarized the scientific data from various animal studies about molecular mechanisms, possible side effects, associations with conventional therapies, and the role of complementary and alternative medicines (CAM) for RA such as ayurvedic medicines in arthritis. In the case of RA, phytochemicals have been shown to act through different pathways such as regulation of inflammatory signaling pathways, T cell differentiation, inhibition of angiogenic factors, induction of the apoptosis of fibroblast-like synoviocytes (FLS), inhibition of autophagic pathway by inhibiting High-mobility group box 1 protein (HMGB-1), Akt/ mTOR pathway and HIF-1α mediated Vascular endothelial growth (VEGF) expression. Also, osteoclasts differentiation is inhibited by down-regulating the VEGF expression by decreasing the accumulation of the ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator)-HIF-1α complex Although phytochemicals have shown to exert potential anti-arthritic activity in many animal models and further clinical data is needed to confirm their safety, efficacy, and interactions in humans.