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ID PMID Title PublicationDate abstract
29951575 Computational Systems Biology Approach for the Study of Rheumatoid Arthritis: From a Molec 2018 In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive literature scanning, strict curation criteria, re-evaluation of previously published attempts and most importantly experts' advice. The RA map will be web-published in the coming months in the form of an interactive map, using the MINERVA platform, allowing for easy access, navigation and search of all molecular pathways implicated in RA, serving thus, as an on line knowledgebase for the disease. Moreover the map could be used as a template for Omics data visualization offering a first insight about the pathways affected in different experimental datasets. The second goal of the project is a dynamical study focused on synovial fibroblasts' behavior under different initial conditions specific to RA, as recent studies have shown that synovial fibroblasts play a crucial role in driving the persistent, destructive characteristics of the disease. Leaning on the RA knowledgebase and using the web platform Cell Collective, we are currently building a Boolean large scale dynamical model for the study of RA fibroblasts' activation.
29692623 Nephritis, cerebritis, and myositis after adalimumab therapy in a patient with rheumatoid 2018 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mainly affects the joints, therefore, may cause deformities and disability if untreated. The first line of treatment is disease-modifying antirheumatic drugs (DMARDs). When the patient fails to respond to DMARDs, mainly methotrexate, then second-line therapy is required. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of RA; however, the treatment with anti-TNFα medications is challenging. It may trigger the autoimmune system and result in producing antibodies that induce symptoms and signs mimic to systemic lupus erythematosus (SLE), and in rare situations can affect vital organs with severe and life-threatening complications. We report on a 38-year-old Saudi woman with longstanding erosive RA, who was diagnosed based on the 1987 classification criteria. She developed life-threatening SLE, and seroconversion of antinuclear antibodies (ANA), anti-double-stranded DNA, with severe systemic involvement (cerebritis, nephritis, myositis, and polyneuropathy), shortly after treatment with adalimumab. Adalimumab was started as anti TNFa therapy (after the failure of traditional therapy), SLE and other autoimmune diseases were ruled out by clinical history, examination, and laboratory investigations, including negative ANAs and anti-double-stranded DNA. When both tests turned out persistently positive even after stopping adalimumab, specific diagnostic and therapeutic modalities were required during her acute illness.
31749869 Modulator role of infliximab and methotrexate through the transient receptor potential mel 2019 Oct INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients. MATERIAL AND METHODS: Neutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA). RESULTS: Intracellular free Ca(2+) concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca(2+) concentrations were further decreased by the ACA therapy. CONCLUSIONS: Our results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca(2+) concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.
30190751 Anti-Cyclic Citrullinated Peptide Antibody and Periodontal Status in Rheumatoid Arthritis 2018 Jul OBJECTIVES: Studies have shown that periodontal disease and Rheumatoid Arthritis (RA) shared similar pathogenesis. Anti-Cyclic Citrullinated Peptide anibodies (anti-CCP) has recently been used for diagnosis of RA. Thus, this study aimed to assess the levels of anti-CCP antibodies and periodontal status in RA patients. METHODS: Forty four RA patients were included in this study. The blood samples were analysed for anti-CCP levels. Plaque Score (PS), Gingivitis Score (GS), Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) were recorded for assessment of periodontal status. Relevant clinical information was obtained from medical records. RESULTS: Mean anti-CCP level was 180.8 ± 290.3 Unit/ml. The results showed that 27.3% patients had poor oral hygiene (PS >60%; mean anti-CCP 84.22 ± 167.51 Unit/ml), 52.3% had generalized gingivitis (mean anti-CCP 145.07 ± 269.17 Unit/ml), and 20.5% had mean CAL of >3mm (mean anti-CCP 56.81 ± 119.02 Unit/ml). None of patients presented with deep PPD > 4mm. The levels of anti-CCP showed no significant association with periodontal status (p=0.27). CONCLUSION: Most RA patients were positive for anti-CCP antibodies and presented with generalized gingivitis. Oral hygiene education should be reinforced in RA patients to prevent further progression of periodontal disease. Nevertheless, studies with larger sample size should be carried out to obtain more conclusive findings.
29456394 Assessment of Vitamin D in Rheumatoid Arthritis and Its Correlation with Disease Activity. 2018 Jan BACKGROUND: Vitamin D is believed to have an immunomodulatory and anti-inflammatory action, and its deficiency has been linked with several autoimmune disorders, including rheumatoid arthritis (RA). The relationship between the severity of RA and serum levels of Vitamin D is a subject of immense interest and therapeutic implications. MATERIALS AND METHODS: This was a prospective, comparative study conducted on 100 participants, 50 cases of RA and 50 healthy controls, all in the age group of 18-75 years. Serum Vitamin D levels were measured and compared in cases and controls. Vitamin D levels in RA patients were also assessed in different stages of disease activity to assess the correlation between the two. RESULTS: Eighty-four percent patients of RA were Vitamin D deficient versus only 34% of controls. The serum Vitamin D levels were also significantly lower in the RA patients (mean value of 21.05 ± 10.02 ng/ml), as compared to the controls (mean value of 32.87 ± 14.16 ng/ml). There was a significant inverse correlation between serum Vitamin D levels and RA disease activity. The mean serum Vitamin D levels were 35.28 ± 9.0 ng/ml, 33.80 ± 4.1 ng/ml, 22.47 ± 6.18 ng/ml, and 14.21 ± 6.97 ng/ml in the remission, low disease activity, moderate disease activity, and high disease activity groups, respectively. CONCLUSIONS: Vitamin D deficiency is more common in RA patients and may be one of the causes leading to development or worsening of the disease.
31497761 Association of Interleukin-17F 7488A/G and 7383A/G Polymorphisms With Rheumatoid Arthritis 2019 Jun OBJECTIVES: This meta-analysis aims to summarize and estimate the relationship between rheumatoid arthritis (RA) susceptibility and two polymorphisms of interleukin-17F (IL-17F) 7488A/G and 7383A/G. MATERIALS AND METHODS: PubMed, Embase and Web of Science were searched up to 01 July 2017. Case-control studies with genotype frequencies data for 7488A/G and 7383A/G were included. The pooled effects were calculated by fixed-effect model or random effects model. RESULTS: A total of seven publications with 1,409 RA patients and 1,303 controls were included in the present meta-analysis. The results indicated that 7488A/G was significantly associated with increased susceptibility to RA (GA vs. AA: odds ratio [OR]=1.43, 95% confidence interval [CI]: 1.07-1.90, p=0.02; GG vs. AA: OR=3.22, 95% CI: 1.54-6.74, p=0.002; GA+GG vs. AA: OR=1.57, 95% CI: 1.02-2.42, p=0.04; GG vs. GA+AA: OR=3.05, 95% CI: 1.46-6.39, p=0.003). In subgroup analysis, 7488A/G was a strong risk factor in Europeans but not in Americans or Africans. No significant association was found between 7383A/G and RA in overall population or ethnic subgroups by all genetic model comparisons. CONCLUSION: This meta-analysis provided evidence that IL-17F 7488A/G polymorphism is associated with increased RA susceptibility, while no clear correlation was found between 7383A/G and RA.
32185327 Exercise participation has increased in patients with Rheumatoid Arthritis: A cross-sectio 2018 Dec OBJECTIVE: This study evaluates exercise participation in patients with rheumatoid arthritis (RA) and the percentage of patients that meet the recommended level of physical activity (at least 150 minutes per week moderate-intensity physical activity) in two cross-sectional questionnaires in 2013 and 2016 in two Dutch RA cohorts. METHODS: In 2013, a cross-sectional study was performed among 740 patients with RA from seven outpatient clinics from the Dutch DREAM registry. Subsequently in 2016, 498 patients with RA of the outpatient clinic of the Bernhoven Hospital (member of the DREAM registry) participated in a similar study. In both years, patients filled in an identical questionnaire about exercise participation (frequency and duration). In 2016, items about self-efficacy to become more physically active were added to the questionnaire. RESULTS: In 2016, patients with RA spent significantly more minutes per week in exercise activities compared to 2013: 180 (150-450) and 120 (60-225) minutes per week, respectively (P<0.001). The percentage of patients with RA who met the recommended physical activity level increased from 25% in 2013 to 57% in 2016. Almost half (44%) of the non-exercisers reported feeling confident to become more physically active. CONCLUSION: Compared to 2013, RA patients participated in 2016 more frequently and spent more minutes per week in exercise activities. This resulted in a higher percentage of patients who met the recommended physical activity level. A personalized physical activity program, with a focus on identifying barriers and setting personal goals, might further increase the physical activity level of patients with RA.
30652022 Switching of biological therapies in Brazilian patients with rheumatoid arthritis. 2019 Jan AIM: To assess drug switching, rates of remission and disease activity in Brazilian patients with rheumatoid arthritis (RA) treated with biologic agents. MATERIALS & METHODS: Using a retrospective method, a total of 94 adult patients were included. RESULTS: Anti-TNF was the first choice therapy in 85 (90.4%) patients. After an average of 8 years of follow-up, 55 (59%) patients were taking anti-TNF, 18 (19%) abatacept, eight (9%) tocilizumab and 13 (14%) rituximab. In this period, 99 switches of biological therapy were registered in 55 patients. CONCLUSION: After 8 years of follow-up, 54% of the RA patients on biological therapy were still experiencing high or moderate activity despite established treatment, including switching between different biologic agents.
30356765 Treatment of Rheumatoid Arthritis Using Combination of Methotrexate and Tripterygium Glyco 2018 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic destructive synovitis and is associated with progressive disability, systemic difficulties, premature death, and socioeconomic costs. Early intervention with disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) and its combination regimen would provide obvious benefits to patients, healthcare systems and society. MTX and tripterygium glycosides tablets (TGT(S)) are most frequently prescribed medicines for RA, and the combination of them occurs frequently in anti-RA prescriptions. While the underlying combination mechanisms and the affected variation of drug blood level remain unclear. According to the American College of Rheumatology criteria for improvement, clinical evaluation following three treatment groups (i.e., MTX and TGT(S) mono- and combined groups) were carried out at baseline and at the end of 12 weeks in a randomized controlled clinical trial. To monitor the affected variation of drug blood level and perturbation of metabolites caused by MTX plus TGT(S) combined to treat active RA, the collected plasma samples were analyzed using RRLC-QqQ-MS and UHPLC-QE Orbitrap HRMS instruments. As a result, 39 metabolites including 7 MTX-related metabolites, 13 TGT(S)-related migratory ingredients and 19 characteristic endogenous metabolites, were quantitatively determined in plasma samples of RA patients after oral administration. The potential mechanism of MTX and TGT(S) combination were preliminarily elucidated on the aspect of clinical biochemical test indicators integrated with quantitative plasma pharmacochemistry and the pseudotargeted metabolomics.
30233732 Dysregulated ICOS(+) proinflammatory and suppressive regulatory T cells in patients with r 2018 Oct Regulatory T cells (Tregs) serve an important role in the pathogenesis of rheumatoid arthritis (RA) by regulating autoimmunity and inflammation. Humans and mice contain inducible T-cell costimulator-positive (ICOS(+)) Tregs, although their role in RA is unclear. A total of 33 patients with RA and 17 normal control (NC) subjects were examined. The proportion of ICOS(+) Tregs in the peripheral blood and intracellular cytokine levels in these cells were assessed using flow cytometry. The percentage of ICOS(+) Tregs increased in the cohort of patients with RA compared with the NCs. Such increases were much larger in patients with inactive RA compared with patients with active RA. Additionally, ICOS(+) Tregs expressed multiple suppressive cytokines, including interleukin (IL)-10, transforming growth factor-β and IL-35, but expressed low levels of IL-17. Importantly, the expression of suppressive cytokines in ICOS(+) Tregs from patients with active RA decreased, but IL-17 expression noticeably increased compared with patients with inactive RA. The present findings suggested that ICOS(+) Tregs may perform inflammatory and inhibitory functions, and abnormal ICOS(+) Tregs numbers and functions may contribute to the pathogenesis of RA.
30207575 Passive Smoking is Responsible for Disease Activity in Female Patients With Rheumatoid Art 2018 Jun OBJECTIVES: This study aims to evaluate the effects of passive smoking on disease activity in female patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: Among a total of 191 female patients with RA (mean age 59.1±12.5 years; range 21 to 87 years) consecutively recruited, 100 female patients (mean age 56.1±13.4 years; range 21 to 87 years) completed the study with mean 17.3 months of follow-up. Patients were classified according to smoking status: current, never, passive, or ex-smoker. Clinical response between never and passive smokers was assessed by disease- activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (DAS28-ESR and DAS28-CRP) and by the European League Against Rheumatism response criteria. RESULTS: Among the 100 female RA patients analyzed, the distribution of smoking status was as follows: current (n=3), never (n=55), passive (n=34), and ex-smokers (n=8). There was no difference of DAS28-ESR and DAS28-CRP between never and passive smokers at baseline. At the time of follow-up, the values of DAS28-ESR and DAS28-CRP in never smokers were significantly decreased than those in passive smokers (p=0.019 and p=0.023, respectively). Patients who never smoked showed a trend to have good or moderate European League Against Rheumatism response without statistical significance, compared to passive smokers (52.7% vs. 32.4%, respectively; p=0.060). CONCLUSION: This preliminary study implicates that passive smoking might be responsible for higher disease activity in female RA patients and never smoking might induce good clinical response in RA.
29872356 Serum heat-shock protein-65 antibody levels are elevated but not associated with disease a 2018 OBJECTIVES: Heat-shock proteins (HSPs) have gained increased interest for their role in autoimmune disorders. These proteins are targeted by the immune system in various autoimmune diseases. The aim of this study was to assess the serum heat-shock protein-65 antibody (anti-HSP65) levels and their clinical significance in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). PATIENTS AND METHODS: A total of 30 patients with RA, 30 patients with AS, and 30 healthy controls were enrolled in this study. All patients were assessed using routine clinical and laboratory evaluations. Serum anti-HSP65 levels were determined by ELISA. RESULTS: Serum anti-HSP65 levels of both RA and AS patients were significantly higher than those of controls (p=0.014 and p=0.001, respectively). No association was found between serum anti-HSP65 levels and disease activity in either RA or AS patients. There was a significant correlation between anti-HSP65 and anti-cyclic citrullinated peptide levels in patients with RA (p=0.024). CONCLUSION: In this study, serum anti-HSP65 levels were increased, but not associated with disease activity in both RA and AS patients. These results suggest that HSP antigens may play a role in the pathogenesis. However, further follow-up studies are needed. Identification of target antigens such as HSP65 is vital to developing new immunotherapeutic agents.
29736348 Improved quality of life and joint functions in patients with knee rheumatoid arthritis wh 2018 OBJECTIVES: To evaluate the outcomes of patients with rheumatoid arthritis (RA) of the knee who underwent five portal arthroscopic synovectomy, with or without post-operative negative pressure drainage (NPD). MATERIAL AND METHODS: A prospective clinical trial was performed. Patients with class I, II, and III RA of the knee were enrolled. They underwent five portal arthroscopic synovectomy. Post-operatively, they received either NPD (group A) or non-NPD (group B). Health assessment questionnaire (HAQ), disease activity score 28 (DAS 28), and Lysholm knee joint score were evaluated before the operations, and at six weeks, three months, and one year after the operations. RESULTS: A total of 36 patients were enrolled into the study, with 63.9% (23) female patients and mean age of 47.2 years old. All of the patients had clinical symptoms (joint swelling, pain, and dysfunction) for at least six months with poor responses to the traditional pharmaceutical therapy. There were 12, 16, and eight patients in class I, II, and III RA groups, respectively (six IA, six IB, eight IIA, eight IIB, four IIIA, and four IIIB). One year after the operation, patients had statistically significant improvements on HAQ, DAS 28, and Lysholm knee joint scores. More improvements were observed in patients with class I diseases. There were no statistically significant differences between group A and B. CONCLUSION: Five portal arthroscopic synovectomy could increase the quality of life, decrease disease activities, and improve joint functions in patients with RA. More benefits were observed in patients with early disease developments. Patients in the NPD group did not show more improvements compared to the patients in the non-NPD group.
29535527 Effects of denosumab on bone metabolism and bone mineral density with anti-TNF inhibitors, 2018 INTRODUCTION: The aim of this 18-month retrospective study was to evaluate the differences in outcomes of denosumab with tumor necrosis factor (TNF) inhibitors (TNFis), tocilizumab (TCZ), or abatacept (ABT) treatment in osteoporosis (OP) patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: Patients were divided into TNFis-treated (TNF group; 44 cases), TCZ-treated (TCZ group; 8 cases), or ABT-treated (ABT group; 14 cases) groups. We measured serum bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) at baseline and every 3 months for 18 months and assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and total hip BMD (H-BMD) at baseline and every 6 months for 18 months. RESULTS: There were no significant differences in the percent changes in BAP, TRACP-5b, or L-BMD among the groups. The percent change in H-BMD was significantly increased in the TCZ group at 12 months or at 12 and 18 months, compared with that in the ABT group or TNF group, respectively. The percent change in L-BMD was significantly increased at 12 months in the TCZ and TNF groups, and at 18 months in all the 3 groups compared with pretreatment levels, whereas the percent change in H-BMD was significantly higher at 6, 12, and 18 months in the TCZ group, at 12 and 18 months in the TNF group, and at 18 months in the ABT group, compared with pretreatment levels. CONCLUSION: Our findings suggest that TCZ might be more useful than TNF or ABT in light of the observed H-BMD increases with denosumab therapy for OP patients with RA.
29470834 Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid A 2018 Jun INTRODUCTION: Post-marketing surveillance (PMS) is an integral part of monitoring adverse events (AEs) following approval of new drugs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). An analysis of PMS reports was conducted to evaluate the safety of tofacitinib in a post-marketing setting. METHODS: Worldwide tofacitinib PMS data received in the Pfizer safety database from November 6, 2012 (first marketing authorization of tofacitinib) to November 5, 2015 were analyzed. Serious AEs (SAEs) of interest were reviewed and reporting rates (RRs) were calculated by dividing the number of SAEs by the estimated 100 patient-years of exposure. Patient exposure was calculated based on estimated worldwide sales and an estimated daily regimen of tofacitinib 5 mg twice daily. RESULTS: During the 3-year reporting period, worldwide post-marketing exposure to tofacitinib since approval was estimated to be 34,223 patient-years. In total, 9291 case reports (82.9% non-serious) were received and 25,417 AEs, 102 fatal cases, and 4352 SAEs were reported. The RRs (per 100 patient-years) for SAEs of interest by Medical Dictionary for Regulatory Activities System Organ Class were 2.57 for infections, 0.91 for gastrointestinal disorders, 0.60 for respiratory disorders, 0.45 for neoplasms, 0.43 for cardiac disorders, and 0.12 for hepatobiliary disorders. CONCLUSIONS: Although there are limitations to these data, no new safety risks were revealed in this real-world setting compared with the safety profile identified in the tofacitinib RA clinical development program. Any risks identified through the tofacitinib development program and PMS will continue to be monitored through pharmacovigilance surveillance. FUNDING: Pfizer Inc.
29540195 Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced 2018 Mar 14 BACKGROUND: Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. METHODS: CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. RESULTS: Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. CONCLUSIONS: Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.
29412789 Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molec 2018 Jan 31 Neuroinflammation plays a crucial role in expression of symptoms of numerous autoimmune and neurodegenerative diseases such as pain during rheumatoid arthritis. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways have been strongly implicated in the generation of pathological pain states, particularly at central nervous system sites and induction of spinal neuroinflammatory symptoms. The wide ranges of research to define new therapeutic approaches, including neuroimmune-modulators like stem cells are in progress. Mesenchymal stem cells conditioned medium (MSC-CM) has anti-inflammatory factors which can regulate the immune responses. The aim of this study was to investigate the effect of administration of MSC-CM on behavioral, cellular and molecular aspects of adjuvant-induced arthritis in male Wistar rats. Complete Freund's adjuvant (CFA)-induced arthritis (AA) was caused by single subcutaneous injection of CFA into the rat's hind paw on day 0. MSC-CM was administered daily (i.p.) and during the 21 days of the study after injection. Hyperalgesia, Edema, Serum TNF-α levels and p38MAPK and NF-κB activities were assessed on days 0,7,14 and 21 of the study. The results of this study indicated the role of MSC-CM in reducing inflammatory symptoms, serum TNF-α levels and activity of intracellular signaling pathway factors during different phases of inflammation caused by CFA. It seems that MSC-CM treatment due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain during CFA-induced arthritis.
30018804 Depression as a risk factor for the development of rheumatoid arthritis: a population-base 2018 OBJECTIVES: Major depressive disorder (MDD) is associated with increased levels of systemic proinflammatory cytokines, including tumour necrosis factor alpha. As these cytokines are pathogenic in autoimmune diseases such as rheumatoid arthritis (RA), our aim was to explore on a population-level whether MDD increases the risk of developing RA. METHODS: A retrospective cohort study was conducted using The Health Improvement Network (THIN) database (from 1986 to 2012). Observation time was recorded for both the MDD and referent cohorts until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, accounting for age, sex, medical comorbidities, smoking, body mass index and antidepressant use. RESULTS: A cohort of 403 932 patients with MDD and a referent cohort of 5 339 399 patients without MDD were identified in THIN. Cox proportional hazards models revealed a 31% increased risk of developing RA among those with MDD in an unadjusted model (HR=1.31, 95% CI 1.25 to 1.36, p<0.0001). When adjusting for all covariates, the risk remained significantly increased among those with MDD (HR=1.38, 95% CI 1.31 to 1.46, p<0.0001). Antidepressant use demonstrated a confounding effect that was protective on the association between MDD and RA. CONCLUSION: MDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.
30697252 Efficacy and safety of various anti-rheumatic treatments for patients with rheumatoid arth 2019 Jan INTRODUCTION: Biologics and traditional disease-modifying anti-rheumatic drugs (DMARDs) are generally used in treating patients with rheumatoid arthritis (RA). Previous studies have presented abundant data and information about the efficacy of such treatments, but the results were incomplete and inconclusive. This network meta-analysis was conducted to compare and assess the efficacy and safety of 15 therapies employing biologics and DMARDs for RA patients. MATERIAL AND METHODS: Six outcomes (American College of Rheumatology 20% response rate (ACR20), ACR50, ACR70, remission, adverse events (AEs) and serious adverse events (SAEs)) were used to evaluate the efficacy and safety of different treatments. The node-splitting method was used to assess the inconsistency, and the rank probabilities of the therapies were estimated by surface under the cumulative ranking curve. Besides, Jadad scale was used to evaluate the methodological quality of eligible studies. RESULTS: A total of 67 randomized controlled trials with 20,898 patients met the inclusion criteria. Most of the therapies presented better performance than conventional DMARDs (cDMARDs) and placebo in ACR20, ACR50 and ACR70. Conversely, the safety of cDMARDs and placebo seemed to be superior in AEs and SAEs. Also, tocilizumab (TCZ) and TCZ + methotrexate (MTX) showed better remission in pain compared to other treatments. Overall, certolizumab pegol (CZP) + MTX and TCZ + MTX had higher probability than the other treatments in efficacy outcomes. CONCLUSIONS: We recommend CZP + MTX as the optimal drug therapy because it has the highest ranking in efficacy outcomes and relatively low risk of adverse events. TCZ + MTX is recommended as an alternative. Abatacept (ABT) and cDMARDs are not recommended due to their low efficacy.
31453503 Diagnosing fibromyalgia in rheumatoid arthritis: The importance of assessing disease activ 2018 Jun OBJECTIVES: This study aims to evaluate fibromyalgia syndrome (FMS) incidence based on 2010 American College of Rheumatology (ACR) criteria in rheumatoid arthritis (RA) patients and the association between FMS with disease activity, functional status and quality of life (QoL). PATIENTS AND METHODS: The study included 151 RA patients (32 males, 119 females; mean age 52.4±12.7 years; range 21 to 82 years) and 77 controls (13 males, 64 females; mean age 53.7±10.2 years; range 33 to 73 years). Individuals were classified into four groups based on presence of RA and FMS. Group 1 included patients with both RA and FMS (n=53), group 2 included patients with RA and without FMS (n=98), group 3 included controls with FMS (n=15), and group 4 included controls without FMS (n=62). Demographic characteristics, morning stiffness (MS), pain, Disease Activity Score 28 (DAS28), functional and QoL scores were compared among the groups. RESULTS: No significant differences were found between the four groups as regards the mean age and gender distribution (p>0.05). Higher pain, MS, DAS28, and QoL scores in the groups with FMS drew attention. While FMS was found in 8.1% of RA patients with remission, it was found in 53.9% of patients with active RA, and in 19.5% of controls. CONCLUSION: Although FMS incidence in patients with RA was higher compared to controls without inflammatory disease, FMS evaluated with 2010 ACR diagnostic criteria was found to be common in the general population. DAS28 and inflammatory markers were higher in RA patients with FMS; thus, it has been concluded that sleep disorder and widespread pain caused by active disease may facilitate the diagnosis of FMS.