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ID PMID Title PublicationDate abstract
31670976 Real-world treatment persistence of non-tumor necrosis factor inhibitors versus tumor necr 2020 Feb Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antirheumatic drug (bDMARD) initiators and switchers.Patients and methods: This retrospective cohort study utilized a national health insurance claims database. Patients aged ≥18 years initiating/switching bDMARD between 1 December 2013 and 31 December 2014, the index period, were followed for 12 months. Initiators who began treatment with a bDMARD during the index period were defined as having no bDMARD prescriptions for the previous year. Switchers who changed treatment from the previous bDMARD to the index bDMARD were defined as having different bDMARDs during the index period. Treatment persistence rates during the follow-up period were measured, and factors associated with non-persistence were assessed with the Cox proportional hazard model.Results: Of 2684 patients, treatment persistence rates were the highest for abatacept in initiators (69.3%) and tocilizumab in switchers (77.0%), while adalimumab showed the lowest persistence rates for both initiators and switchers (48.2%, 28.8%), followed by etanercept (51.3%, 41.0%). Adalimumab and etanercept were significantly more likely to show non-persistence (HR 1.58, 95% CI 1.27-1.96; HR 1.42, 95% CI 1.14-1.76) compared to infliximab for initiators, while tocilizumab was significantly more likely to show persistence (HR 0.411, 95% CI 0.206-0.819) in switchers.Conclusions: Non-TNF inhibitors showed higher persistence rates than TNF inhibitors in South Korean RA patients, and tocilizumab especially was associated with higher persistence in patients with inadequate response to TNF inhibitors. Good persistence with non-TNF inhibitors indicates the potential for long-term efficacy as first-line treatment.
32503893 Upregulated PKM2 in Macrophages Exacerbates Experimental Arthritis via STAT1 Signaling. 2020 Jul 1 Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis. We hypothesize that Pkm2, as a key regulatory enzyme of glycolysis pathway, triggers the activation of macrophages (Mφ), which results in proinflammatory cytokine production during the arthritis progress. In this study, Pkm2 was found to be overexpressed in ED1-positive Mφ in spleens and synovial tissues from arthritic rats via immunofluorescence, Western blotting, and quantitative RT-PCR. To reveal the role of Pkm2, Dark Agouti rats were treated with either Pkm2 enzyme inhibitor shikonin or the RNA interference plasmids of Pkm2 and negative control plasmids, respectively, via i.p. injection. Pkm2 intervention could alleviate the severity of pristane-induced arthritis in aspects of the macroscopic arthritis score, perimeter changes of midpaw, and the synovitis and destruction of the bone and cartilage as well as reduce the ED1 and p-Stat1-positive cell population in rat synovial tissues. Silencing Pkm2 by RNA interference in classical activated rat and mouse Mφ resulted in less Tnf-α, Il-1β production via Stat1 signaling. Collectively, Pkm2 is highly expressed in ED1-positive Mφ of spleens and synovial tissues from arthritic rats and promotes Mφ activation via Stat1 signaling. Pkm2 might be a promising selective metabolic target molecule for rheumatoid arthritis treatment.
32805045 Nonvitamin, Nonmineral Dietary Supplement Use in Individuals with Rheumatoid Arthritis. 2020 Sep 1 BACKGROUND: Over-the-counter, natural product-based (nonvitamin, nonmineral) dietary supplement (NVNM DS) use is common in adults with rheumatoid arthritis (RA), a group at risk for drug-DS interactions, due to polypharmacy, but this use is underreported to health care providers. Recent dramatic changes in US sales of specific NVNM DS suggest that the prevalence and types of NVNM DS used in RA populations may also have shifted. OBJECTIVES: A study was undertaken to identify current and past use of specific NVNM DS for RA disease treatment and to examine associations between use of NVNM DS, RA pharmaceuticals, and/or vitamin or mineral (VM) DS. METHODS: We developed a survey instrument to capture current and ever use of specific NVNM DS, VM DS, and RA pharmaceuticals, with 696 subjects self-reporting an RA diagnosis recruited online or in clinic for survey participation. Analyses were limited to 611 subjects reporting RA diagnosis after age 18 y and treatment with specific RA pharmaceuticals. RESULTS: Most participants reported DS use, with current usage prevalence 49.6% (n = 303), 83.5% (n = 510), or 87.6% (n = 535) for NVNM, VM, or any DS, respectively. While not having appeared in previous RA surveys, turmeric and ginger were among the top 3 NVNM DS in current use, along with fish oil/ω-3 (n-3) PUFA. Concurrent NVNM DS use was reported by 48.2% (n = 243) of participants currently using RA pharmaceuticals (n = 504) and was more common in those using disease-modifying antirheumatic drugs only (no biologics). Most methotrexate users (83%) reported concurrent folate supplementation, with one-third also using turmeric, which is notable because methotrexate and turmeric have been associated with hepatotoxicity. CONCLUSION: Individuals with RA commonly use NVNM DS in combination with RA pharmaceuticals, including a previously undocumented but popular use of turmeric or ginger supplements with an unclear risk/benefit ratio.
32291099 Effect of statin use on the risk of rheumatoid arthritis: A systematic review and meta-ana 2020 Dec OBJECTIVES: Anti-inflammatory and immune-modulating effects of statins suggest that they may play a role in the risk of rheumatoid arthritis (RA). We aimed to perform a systematic review and meta-analysis of studies assessing the risk of RA in statin-users versus non-users. METHODS: We searched Medline from inception to 01/22/2019 and Embase from 1988 to Week 03 2019 for studies that examined the association between statin use and RA without restrictions on language. RESULTS: We identified 1,161 references; of them 8 studies (5 cohort studies and 3 case-control studies) were included in the systematic review. Four cohort studies comparing statin-users versus non-users were included in the meta-analysis. The pooled risk ratio (RR) was 1.01; 95%CI 0.93-1.10; I(2) = 17%. Case-control studies showed highly heterogeneous results (I(2) = 92%) and were not included in the meta-analysis. One cohort study and one case-control study assessing persistence with or intensity of treatment with statins showed lower risk of RA with higher versus lower treatment persistence or intensity of statin use (pooled RR 0.66; 95%CI 0.5-0.87; I(2) = 83%). The certainty in the evidence was low. CONCLUSION: In this systematic review and meta-analysis, we observed no difference in risk of RA in statin users vs non-users. Risk of RA may be lower in patients with higher versus lower statin treatment persistence or intensity. Future observational studies with guards against selection bias and confounding are needed to further elucidate the impact of statin use on the risk of RA, considering potential differences by dosage, duration of use, study population and other factors.
32513309 Differential long-term retention of biological disease-modifying antirheumatic drugs in pa 2020 Jun 8 BACKGROUND: The effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) by age group (< 65, 65-74, and ≥ 75 years) are uncertain. We examined retention rates reflecting the effectiveness and safety of bDMARDs in actual clinical practice for clarifying optimal therapeutic strategies for rheumatoid arthritis (RA) by age groups. METHODS: Data of patients who were treated with tumor necrosis factor inhibitors (TNFi), abatacept (ABA), and tocilizumab (TCZ) between February 2011 and April 2017 were collected from a prospective observational registry of RA patients. A total of 1362 patients were enrolled, of which 695 were aged < 65 years, 402 were aged 65-74 years, and 265 were aged ≥ 75 years. Primary outcome was the drug retention rate in adjusted data using inverse probability of treatment weighting based on generalized propensity scores. RESULTS: In patients aged < 65 years, 3-year retention rates of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively (ABA versus TCZ, p = 0.017; TNFi versus TCZ, p = 0.002). In patients aged 65-74 years, 3-year retention rates of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively (TCZ versus TNFi, p = 0.034). In patients aged ≥ 75 years, 3-year retention rates for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively (ABA versus TNFi, p = 0.017). CONCLUSIONS: We found that the effectiveness and safety of TCZ were maximal in patients aged < 75 years and that patients aged ≥ 75 years might be suitable candidates for TCZ and ABA therapy. The use of therapeutic strategies appropriate to each age group might improve the outcomes of bDMARD therapy for RA.
31175635 Serious Selenium Deficiency in the Serum of Patients with Kashin-Beck Disease and the Effe 2020 Mar To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.
32541503 Traditional Chinese medicine on treating active rheumatoid arthritis: A protocol for syste 2020 Jun 12 BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with progressive joint damage and disability. There is a lack of effective methods in the treatment of RA currently. Many clinical trials have proved that traditional Chinese medicine (TCM) has obvious advantages in the treatment of RA. In this systematic review, we intend to evaluate the efficacy and safety of TCM for active RA. METHODS: We will search PubMed, the Cochrane Library, Embase, Web of Science, the Chinese National Knowledge Infrastructure Database, Wanfang Data, and Chinese Science and Technology Periodical Database. Simultaneously we will retrieval relevant meeting minutes, eligible research reference lists, symposium abstracts, and grey literatures. Included criteria are randomized controlled trials (RCTs) about TCM for active RA to assess its efficacy and safety. We will use the Revman 5.3 and Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The Grading of Recommendations Assessment, Development, and Evaluation standard will be used to evaluate the quality of evidence. RESULTS: This systematic review will provide a synthesis of TCM for patients with active RA from various evaluation aspects including tender joint count, swollen joint count, RF, CRP, ESR, DAS28, TCM syndrome evaluation criteria, and adverse events. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of TCM in the treatment of patients with active RA. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019146726.
32860421 Model-Based Meta-Analysis Compares DAS28 Rheumatoid Arthritis Treatment Effects and Sugges 2021 Feb A nonlinear mixed effects modeling approach was used to conduct a model-based meta-analysis (MBMA) of longitudinal, summary-level, baseline-corrected 28-joint Disease Activity Score (ΔDAS28) clinical trial data from seven approved rheumatoid arthritis (RA) drugs (abatacept, adalimumab, certolizumab, etanercept, rituximab, tocilizumab, and tofacitinib), representing 130 randomized clinical trials in 27,355 patients. All of the drugs except tocilizumab were found to have relatively similar ΔDAS28 time courses and efficacy (baseline-corrected and placebo-corrected) at 24 weeks and beyond of approximately 0.87-1.3 units in the typical RA patient population. Tocilizumab was estimated to have a differentially greater response of 1.99 at 24 weeks, likely due to its disproportionate effect on the acute-phase cytokine interleukin-6. Baseline DAS28, disease duration, percentage of male participants, and the year of conduct of the trial were found to have statistically significant effects on the timing and/or magnitude of ΔDAS28 in the control arms. Clinical trial simulations using the present MBMA indicated that abatacept, certolizumab, etanercept, tocilizumab, and tofacitinib would be expected to have a greater than 70% probability of showing a statistically significant difference vs. control at Week 6 with a sample size of ~ 30 patients per arm. In future RA clinical trials, an interim analysis conducted as early as 6 weeks after treatment initiation, with relatively small sample sizes, should be sufficient to detect the ΔDAS28 treatment effect vs. placebo.
33025679 Twenty-Four Hour Activity and Sleep Profiles for Adults Living with Arthritis: Habits Matt 2020 Dec OBJECTIVE: To identify 24-hour activity-sleep profiles in adults with arthritis and explore factors associated with profile membership. METHODS: Our study comprised a cross-sectional cohort and used baseline data from 2 randomized trials studying activity counseling for people with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or knee osteoarthritis (OA). Participants wore activity monitors for 1 week and completed surveys for demographic information, mood (Patient Health Questionnaire 9), and sitting and walking habits (Self-Reported Habit Index). A total of 1,440 minutes/day were stratified into minutes off body (activity unknown), sleeping, resting, nonambulatory, and intermittent or purposeful ambulation. Latent class analysis determined cluster numbers; baseline-category multinomial logit regression identified factors associated with cluster membership. RESULTS: Our cohort included 172 individuals, including 51% with RA, 30% with OA, and 19% with SLE. We identified 4 activity-sleep profiles (clusters) that were characterized primarily by differences in time in nonambulatory activity: high sitters (6.9 hours sleep, 1.6 hours rest, 13.2 hours nonambulatory activity, and 1.6 hours intermittent and 0.3 hours purposeful walking), low sleepers (6.5 hours sleep, 1.2 hours rest, 12.2 hours nonambulatory activity, and 3.3 hours intermittent and 0.6 hours purposeful walking), high sleepers (8.4 hours sleep, 1.9 hours rest, 10.4 hours nonambulatory activity, and 2.5 hours intermittent and 0.3 hours purposeful walking), and balanced activity (7.4 hours sleep, 1.5 hours sleep, 9.4 hours nonambulatory activity, and 4.4 hours intermittent and 0.8 hours purposeful walking). Younger age (odds ratio [OR] 0.95 [95% confidence interval (95% CI) 0.91-0.99]), weaker occupational sitting habit (OR 0.55 [95% CI 0.41-0.76]), and stronger walking outside habit (OR 1.43 [95% CI 1.06-1.91]) were each associated with balanced activity relative to high sitters. CONCLUSION: Meaningful subgroups were identified based on 24-hour activity-sleep patterns. Tailoring interventions based on 24-hour activity-sleep profiles may be indicated, particularly in adults with stronger habitual sitting or weaker walking behaviors.
32541078 Whole-body Magnetic Resonance Imaging in Psoriatic Arthritis, Rheumatoid Arthritis, and He 2021 Feb OBJECTIVE: Whole-body MRI (WBMRI) is a promising technique for monitoring patients' global disease activity in inflammatory joint diseases. The validation of WBMRI is limited; no studies have evaluated the test-retest agreement (interscan agreement) and only a few have assessed the intra- and interreader agreement. Therefore, we first examined the interscan agreement of WBMRI in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and healthy controls (HC); and second, we evaluated the intra- and interreader agreement and agreement with conventional hand MRI and determined the distribution of lesions. METHODS: WBMRI was performed twice at a 1-week interval in 14 patients with PsA, 10 with RA, and 16 HC. Images were anonymized and read in pairs with unknown chronological order by experienced readers according to the Outcome Measures in Rheumatology (OMERACT) WBMRI, Canada-Denmark MRI, and the RA MRI scoring system (RAMRIS) and the PsA MRI scoring system (PsAMRIS). Ten image sets were reanonymized for assessment of intra- and interreader agreement. Agreement was calculated on lesion level by percentage exact agreement (PEA) and Cohen κ, and for sum scores by absolute agreement, single-measure intraclass correlation coefficient (ICC). RESULTS: WBMRI of the spine and peripheral joints and entheses generally showed moderate to almost perfect interscan agreement with PEA ranging from 95% to 100%, κ 0.71-1.00, and ICC 0.95 to 1.00. Intra- and interreader data generally showed moderate to almost perfect agreement. Agreement with conventional MRI varied. More lesions were found in patients than in HC. CONCLUSION: WBMRI showed good interscan agreement, implying that repositioning of the patient between examinations does not markedly affect scoring of lesions. Intra- and interreader agreement were moderate to almost perfect.
32711255 Microbiota-derived butyrate limits the autoimmune response by promoting the differentiatio 2020 Aug BACKGROUND: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder with a high prevalence, especially in industrialized countries. Dysbiosis of the intestinal microbiota has been observed in RA patients. For instance, new-onset untreated RA (NORA) is associated with the underrepresentation of the Clostridium cluster XIVa, including Lachnospiraceae, which are major butyrate producers, although the pathological relevance has remained obscure. Follicular regulatory T (T(FR)) cells play critical regulatory roles in the pathogenesis of autoimmune diseases, including RA. Reduced number of circulating T(FR) cells has been associated with the elevation of autoantibodies and disease severity in RA. However, the contribution of commensal microbe-derived butyrate in controlling T(FR) cell differentiation remains unknown. METHODS: We examined the contribution of microbe-derived butyrate in controlling autoimmune arthritis using collagen-induced arthritis (CIA) and SKG arthritis models. We phenotyped autoimmune responses in the gut-associated lymphoid tissues (GALT) in the colon and joint-draining lymph nodes in the CIA model. We developed an in vitro CXCR5(+)Bcl-6(+)Foxp3(+) T(FR) (iT(FR)) cell culture system and examined whether butyrate promotes the differentiation of iT(FR) cells. FINDINGS: Microbe-derived butyrate suppressed the development of autoimmune arthritis. The immunization of type II collagen (CII) caused hypertrophy of the GALT in the colon by amplifying the GC reaction prior to the onset of the CIA. Butyrate mitigated these pathological events by promoting T(FR) cell differentiation. Butyrate directly induced the differentiation of functional T(FR) cells in vitro by enhancing histone acetylation in T(FR) cell marker genes. This effect was attributed to histone deacetylase (HDAC) inhibition by butyrate, leading to histone hyperacetylation in the promoter region of the T(FR)-cell marker genes. The adoptive transfer of the butyrate-treated iT(FR) cells reduced CII-specific autoantibody production and thus ameliorated the symptoms of arthritis. INTERPRETATION: Accordingly, microbiota-derived butyrate serves as an environmental cue to enhance T(FR) cells, which suppress autoantibody production in the systemic lymphoid tissue, eventually ameliorating RA. Our findings provide mechanistic insights into the link between the gut environment and RA risk. FUNDING: This work was supported by AMED-Crest (16gm1010004h0101, 17gm1010004h0102, 18gm1010004h0103, and 19gm1010004s0104 to KH), the Japan Society for the Promotion of Science (JP17KT0055, JP16H01369, and JP18H04680 to KH; JP17K15734 to DT), Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects (KH), Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research (DT), the SECOM Science and Technology Foundation (KH), the Cell Science Research Foundation (KH), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (DT), the Suzuken Memorial Foundation (KH and DT), the Takeda Science Foundation (KH and DT), The Science Research Promotion Fund, and The Promotion and Mutual Aid Corporation for Private Schools of Japan (KH).
31244428 Methotrexate Hepatotoxicity in Rheumatoid Arthritis: An Analysis of the Physicians' Policy 2020 BACKGROUND: Methotrexate hepatotoxicity could be a reason for the discontinuation or dose reduction in patients with Rheumatoid Arthritis (RA); however, the consequence of different policies in this situation is unclear and the physicians need to know what would happen after their decision. OBJECTIVE: To demonstrate the consequence of multiple approaches towards transaminitis management in patients with RA receiving Methotrexate (MTX). METHODS: Data were obtained from the previous work (2006) on 295 patients with RA undergoing MTX treatment. Those who developed transaminitis at least one time were selected for this study. Then, the physicians' decisions regarding discontinuing, decreasing, or prescribing a fixed dose of MTX along with the effect of each decision on the next liver enzyme were evaluated. RESULTS: Strategies of decreasing dose or discontinuing MTX were adopted in 31.4% of patients and prescribing fixed dose was done in 53.9% of patients, leading to 93% and 65% next enzyme normalization, respectively. Thirty-four patients had definite MTX induced transaminitis and 55.9% of the physicians decided to decrease MTX dose for them, causing normalization of the next enzyme in 83% of these patients. In contrast, continuing MTX, even with the same dose, in definite MTX induced transaminitis cases led to consecutive enzyme elevations in 88.9% of these patients (p=0.001). CONCLUSION: Normalization of liver enzymes was observed after decreasing dose or discontinuing MTX, suggesting this policy as the best practice for the management of MTX induced transaminitis. However, the trend to improvement, despite the type of physicians' decision, was observed. This trend was not found in definite MTX induced transaminitis, revealing the prominence of the physician's policy in this situation.
32911288 Discontinuation of biologic therapy due to lack/loss of response and adverse events is sim 2020 Oct OBJECTIVES: Time to discontinuation of biologic therapy may be related to mechanism of action. We aimed to compare discontinuation of tumor necrosis factor inhibitors (TNFi) versus non-TNFi in an observational rheumatoid arthritis cohort. METHODS: Patients enrolled in the Ontario Best Practices Research Initiative (OBRI) starting biologic agents on or after 1st January 2010 were included. Time to discontinuation due to (1) any reason, (2) any of lack/loss of response, adverse events (AEs), physician, or patient decision, (3) lack/loss of response, and (4) AEs were assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. RESULTS: A total of 932 patients were included of whom 174 (18.7%) received non-TNFi and 758 (81.3%) received TNFi. Over a median follow-up of 1.7 years, discontinuation was reported for 416 (44.6%) due to any reason, 367 (39.4%) due to any of lack/loss of response, AEs, physician, or patient decision, 192 (20.6%) due to lack/loss of response, and 102 (10.9%) due to AEs. After adjusting for propensity score, there was no significant difference in discontinuation between the two classes due to any reason [HR 1.14 (0.90-1.46), p = 0.28], lack/loss of response [HR: 1.01 (0.70-1.47), p = 0.95], and AEs [HR: 1.06 (0.64-1.73), p = 0.83]. Similar results were found in biologic naïve patients. CONCLUSIONS: This analysis demonstrates that discontinuation of therapy is similar in patients started on TNFi and non-TNFi therapies. There was also no significant difference in stopping due to lack/loss of response or AEs, suggesting that these reasons should not drive the selection of one treatment over another.
32131890 Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arth 2020 Mar 4 BACKGROUND: With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs. METHODS: This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints-C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group. RESULTS: Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity. CONCLUSIONS: In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.
32373221 Identification of a novel microRNA-141-3p/Forkhead box C1/β-catenin axis associated with 2020 Rationale: Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis in which synovial fibroblasts (SFs) play key roles in cartilage and bone destruction through tumor-like proliferation, migration, invasion and inflammation. This study aimed to research forkhead box protein C1 (FoxC1) and microRNA (miR)-141-3p, which modulate pathological changes in the synovial membrane, to find possible strategies for treating RA. Methods: FoxC1, β-catenin and miR-141-3p gene expression in synovial tissues and SFs was quantified by real-time PCR; FoxC1 and β-catenin protein levels were evaluated by immunohistochemistry, immunofluorescence, and Western blotting. We transiently transfected human SFs with FoxC1 and β-catenin overexpression and silencing vectors and assessed proliferation, migration, invasion and inflammation by cell function and enzyme-linked immunosorbent assays. We also assessed downstream signaling activation using immunofluorescence, real-time PCR and Western blotting. Double luciferase, coimmunoprecipitation and chromatin immunoprecipitation assays were used to verify miR-141-3p, FoxC1 and β-catenin gene and protein combinations. Finally, the therapeutic effects of FoxC1 silencing and miR-141-3p overexpression were evaluated in type II collagen-induced arthritis (CIA) rats. Results: We found that FoxC1 expression was significantly upregulated in synovium and SFs in both RA patients and rats with collagen-induced arthritis (CIA). FoxC1 overexpression increased β-catenin messenger RNA (mRNA) and protein levels and upregulated cyclin D1, c-Myc, fibronectin and matrix metalloproteinase 3 (MMP3) mRNA and protein expression in RA SFs (RASFs). In contrast, FoxC1 knockdown reduced β-catenin mRNA and protein levels as well as cyclin D1, c-Myc, and fibronectin mRNA and protein levels in RASFs. Furthermore, altering FoxC1 expression did not significantly change GSK3β and pGSK3β levels. FoxC1 overexpression promoted proliferation, migration, invasion and proinflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)) production and reduced anti-inflammatory cytokine (IL-10) levels in RASFs. FoxC1 bound to the β-catenin promoter, and β-catenin mediated the FoxC1-induced pathological changes. We also observed downregulated microRNA (miR)-141-3p expression in SFs from both RA patients and CIA rats and further found that miR-141-3p bound to the FoxC1 3'UTR and suppressed FoxC1 expression. Intra-ankle miR-141-3p agomir or FoxC1-specific siRNA injection hindered CIA development in rats. Conclusions: FoxC1 and miR-141-3p participate in RA pathogenesis by mediating inflammation and SF proliferation, migration, and invasion and thus could be novel targets for RA therapy as a nonimmunosuppressive approach.
32586308 Methodological and reporting quality evaluation of meta-analyses on the Chinese herbal pre 2020 Jun 26 BACKGROUND: Zheng Qing Feng Tong Ning (ZQFTN) is a sinomenine (SIN) preparation that has been used in clinical practice. Our study aimed to assess the methodological and reporting quality of meta-analyses on the Chinese herbal formula ZQFTN for the treatment of rheumatoid arthritis (RA). METHODS: Systematic searches were carried out with the 5 following electronic databases from inception to July 2019: China National Knowledge Infrastructure (CNKI), Wanfang, VIP database for Chinese technical periodicals (VIP), Cochrane Library and PubMed. The quality of the methodology and reporting was measured with the assessment of multiple systematic reviews 2 (AMSTAR 2) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Eight studies were identified. Among the 16 items of the AMSTAR 2 scale, four items were optimally reported ("Y" =100% of the items), and another four items were poorly reported ("Y" =0% of the items). Only 2 studies received a good overall score ("Y" ≥50% of the items). Regarding the PRISMA statement, the scores of 5 studies were lower than the average score (17.69), indicating that the quality of the reports was very low. In terms of the GRADE, none of the 61 results were of high quality (0.0%). Fifteen results were of medium quality (25%), 34 were of low quality (55%), and 12 were of very low quality (20%). Among the five downgrading factors, deviation risk (n = 61, 100%) was the most common downgrading factor, followed by inconsistency (n = 30, 50%), publication bias (n = 17, 28%), inaccuracy (n = 11, 18%) and indirectness (n = 0, 0%). CONCLUSIONS: The methodological and reporting quality of the meta-analyses and systematic reviews in the included studies are less than optimal, and researchers should undergo additional training and follow the AMSTAR 2 scale, PRISMA statement and GRADE to design high-quality studies in the future.
32776484 Surgical Management of Monoarticular Rheumatoid Arthritis of the Fifth Metatarsophalangeal 2020 Dec OBJECTIVE: To investigate the clinical and radiological outcomes in patients with monoarticular rheumatoid arthritis of the fifth metatarsophalangeal joint after Weil osteotomy. METHODS: From July 2011 to September 2015, 18 feet of 16 rheumatoid arthritis patients who underwent Weil osteotomy of the fifth metatarsal toe with a mean age at the time of surgery of 48.8 ± 7.4 years were reviewed retrospectively. The mean disease duration was 44.6 ± 6.8 months, and the follow-up period was 36 months. Clinical outcomes were evaluated according to the American Orthopaedic Foot and Ankle Society lesser metatarsophalangeal interphalangeal scale (AOFAS), 10-item SF-36 physical functioning and 2-item SF-36 bodily pain, Visual Analogue Scale (VAS), and satisfaction scores. In the radiologic evaluation, fifth metatarsophalangeal angle (MTP-5), lateral deviation angle (LDA), and longitudinal axes of the fifth metatarsal were measured on anterior-posterior (AP) weight-bearing radiographs preoperative and at the last follow-up. RESULTS: Clinical assessment showed that the total average of AOFAS was significantly increased from preoperative 53.6 ± 9.0 to 98.7 ± 2.0 points, and the VAS score was significantly decreased from preoperative 4.1 ± 1.5 to 1.1 ± 0.8 points at the last follow-up (P < 0.001). The total averages of SF-36 physical functioning and SF-36 bodily pain were significantly increased from preoperative 48.9 ± 9.0 to 99. ± 2.1 and from 61.4 ± 12.1 to 99.4 ± 2.4 points, respectively, at the last follow-up (P < 0.001). Subjectively, the excellent outcome of the surgery results were rated by 13 patients (81.3%) that underwent surgery and three patients (18.7%) were rated as good. Regarding radiographic parameters, the mean MTP-5 significantly decreased from 21.5° ± 1.2° preoperatively to 10.2° ± 1.2°, the mean LDA significantly decreased from 7.1° ± 1.2° preoperatively to -2.4° ± 1.0°, and the mean length of the fifth metatarsal was significantly shortened from 71.5 ± 1.4 preoperatively to 67.8 ± 1.5 mm at the final follow-up visit (P < 0.001). No malunion, nonunion, necrosis, pseudoarthrosis, or fracture of the fifth metatarsal was found. No exuberant bone growth, perforation of the screw, subluxation, or dislocation was observed. No indications of modification, revision or repeat surgery, or delayed wound healing were observed during follow-up period. CONCLUSION: Surgical management of the monoarticular rheumatoid arthritis of the fifth metatarsophalangeal joint can achieve good clinical and radiological outcomes, with pain relief and dislocation reduction, as well as high satisfaction and improvement without recurrence or progression during the follow-up period.
32803571 Overall survival in patients with rheumatoid arthritis and solid malignancies receiving bi 2020 Oct INTRODUCTION/OBJECTIVES: The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs. METHODS: We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate. RESULTS: We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1 years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively. CONCLUSION: No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points •We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. •Most patients who received bDMARDs had been diagnosed with early stage cancer •As few patients with advanced cancer received bDMARDs safety for this group cannot be established •No significant differences were observed between TNFi and nonTNFi, but the sample size was small.
33613566 Interleukin-17A Interweaves the Skeletal and Immune Systems. 2020 The complex crosstalk between the immune and the skeletal systems plays an indispensable role in the maintenance of skeletal homeostasis. Various cytokines are involved, including interleukin (IL)-17A. A variety of immune and inflammatory cells produces IL-17A, especially Th17 cells, a subtype of CD4(+) T cells. IL-17A orchestrates diverse inflammatory and immune processes. IL-17A induces direct and indirect effects on osteoclasts. The dual role of IL-17A on osteoclasts partly depends on its concentrations and interactions with other factors. Interestingly, IL-17A exerts a dual role in osteoblasts in vitro. IL-17A is a bone-destroying cytokine in numerous immune-mediated bone diseases including postmenopausal osteoporosis (PMOP), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). This review will summarize and discuss the pathophysiological roles of IL-17A on the skeletal system and its potential strategies for application in immune-mediated bone diseases.
31498447 Real-world evidence for increased deep neck infection risk in patients with rheumatoid art 2020 Jun OBJECTIVE: To investigate the association between rheumatoid arthritis (RA) and deep neck infection (DNI). STUDY DESIGN: Retrospective cohort study. METHODS: Patients newly diagnosed with RA between 2000 and 2011 were identified from the National Health Insurance Research Database in Taiwan. Moreover, patients without RA were randomly selected and matched at a 1:4 ratio by age, sex, urbanization level, income, and diabetes mellitus. The patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of DNI. RESULTS: In total, 30,207 patients with RA and 120,828 matched patients without RA were enrolled. Patients with RA had a significantly higher cumulative incidence of DNI than those without RA (P < 0.001). The adjusted Cox proportional hazard model demonstrated that RA was significantly associated with a higher incidence of DNI (hazard ratio: 2.80, 95% confidence interval: 2.26-3.46, P < 0.001). Therapeutic methods (surgical or nonsurgical) did not differ significantly between the patients with RA-DNI and with non-RA-DNI. Patients with RA-DNI had higher rates of tracheostomy, mediastinitis, mediastinitis-related mortality, and mortality than patients with non-RA-DNI, although these differences were without statistical significance. RA patients receiving no therapy experienced higher rates of DNI compared with those receiving methotrexate alone, disease-modifying antirheumatic drugs, or biologic therapies. CONCLUSION: This study is the first to investigate the association between RA and DNI. We conclude RA is an independent predisposing factor for DNI. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1402-1407, 2020.