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ID PMID Title PublicationDate abstract
33547228 Value of MRI and ultrasound for prediction of therapeutic response and erosive progression 2021 Feb OBJECTIVES: To investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression. METHODS: In a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses. RESULTS: Baseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes. CONCLUSIONS: Imaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA.
34526397 Radiographic Progression of Structural Joint Damage Over 5 Years of Baricitinib Treatment 2022 Feb OBJECTIVE: To evaluate the effect of baricitinib on inhibiting radiographic progression of structural joint damage over 5 years in patients with active rheumatoid arthritis (RA). METHODS: Patients completed 1 of 3 phase III baricitinib trials (ClinicalTrials.gov: NCT01711359, NCT01710358, or NCT01721057) and entered the long-term extension RA-BEYOND (NCT01885078), in which patients received once-daily 4 mg or 2 mg baricitinib. Across these trials, patients initially receiving methotrexate (MTX) or adalimumab (ADA) switched to baricitinib 4 mg at Week 52. Patients initially receiving placebo (PBO) switched to baricitinib 4 mg at Week 24. Radiographs were scored at baseline and Years 2, 3, 4, and 5. Change from baseline in van der Heijde modified total Sharp score (ΔmTSS) was computed. RESULTS: Overall, 2125 of 2573 (82.6%) randomized patients entered RA-BEYOND; 1837 of 2125 (86.4%) entered this analysis. From Years 3 to 5, higher proportions of disease-modifying antirheumatic drug (DMARD)-naïve patients on initial baricitinib (monotherapy or with MTX) had no progression vs initial MTX (ΔmTSS ≤ 0 at Year 5: 59.6% baricitinib 4 mg; 66.2% baricitinib 4 mg + MTX; 40.7% MTX). Higher proportions of patients with inadequate response (IR) to MTX on initial baricitinib or ADA vs PBO had no progression (ΔmTSS ≤ 0 at Year 5: 54.8% baricitinib 4 mg; 55.0% ADA; 50.3% PBO). Higher proportions of patients with conventional synthetic DMARD-IR on initial baricitinib 4 mg had less progression vs initial PBO or baricitinib 2 mg (ΔmTSS ≤ 0 at Year 5: 66.7% baricitinib 4 mg; 58.2% baricitinib 2 mg; 60.0% PBO). CONCLUSION: Oral baricitinib maintained lower levels of radiographic progression than initial conventional synthetic DMARD or PBO through 5 years in patients with active RA.
34453959 Molecular toxicity of methotrexate in rheumatoid arthritis treatment: A novel perspective 2021 Sep Rheumatoid arthritis (RA) is an autoimmune inflammatory systematic complication which is a chronic disorder that severely affects bones and joints and results in the quality of life impairment. Methotrexate (MTX), an FDA-approved drug has maintained the standard of care for treating patients affected with RA. The mechanism of MTX includes the inhibition of purine and pyrimidine synthesis, suppression of polyamine accumulation, promotion of adenosine release, adhesion of the inflammatory molecules, and controlling of cytokine cascade in RA. The recommended dose for RA patients is 5-25 mg of MTX per week, depending on the severity of the disease but MTX has proven to be cytotoxic with side effects affecting various tissues when treating RA patients even with low doses over a prolonged period of time. The mechanism of such toxicity is not entirely understood. This review strives to understand it by correlating the different pathways, including MTX in folate metabolism, Sirt1/Nrf2/γ-gcs, and γ-gcs/CaSR-TNF-α/NF-kB signaling. In addition to this, the importance of targeted therapy combination with MTX on RA treatment and combinations approved from the clinical trials are also briefly discussed. Overall, this review elucidates the various MTX molecular mechanisms and toxicity at the molecular level, the limitations, and the scope for future directions.
34521259 Genome-wide association study of liver enzyme elevation in rheumatoid arthritis patients s 2021 Oct Aim: To identify novel genetic variants predisposing to elevation of Alanine aminotransferase (ALT) in rheumatoid arthritis (RA) patients after initiation of methotrexate (MTX) treatment. Patients & methods: We performed genome-wide association studies in 198 RA patients starting MTX. Outcomes were maximum level of ALT and ALT >1.5-times the upper level of normal within the first 6 months of treatment. Results: RAVER2 (rs72675408) was significantly associated with maximum level of ALT (p = 4.36 × 10(-8)). This variant is in linkage disequilibrium with rs72675451, which is associated with differential expression of JAK1 and RAVER2. Conclusion: We found an association between ALT elevation and genetic variants that may regulate the expression of JAK1 and RAVER2. JAK1 encodes a janus kinase involved in the pathogenesis of RA.
34114403 Zhuifeng Tougu capsules improve rheumatoid arthritis symptoms in rats by regulating the to 2021 Jun OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules (, ZFTG) in the treatment of rheumatoid arthritis (RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B (TLR2/4-NF-κB) signaling pathway. METHODS: Type Ⅱ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-, and low-dose ZFTG groups. The methotrexate (MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index (AI) score were measured. The production of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factors (RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by Western blotting, and the mRNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction. RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased (P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident (P < 0.01). CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway.
34581056 [Therapeutic mechanism of Psammosilene tunicoides extract on rheumatoid arthritis based on 2021 Sep In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1β and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1β and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.
34410943 CLIC1 Expression in Skin Biopsies from Patients With Rheumatoid and Psoriatic Arthritis as 2021 Sep BACKGROUND/AIM: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients' skin with vasculitis and its variability depending on the therapy used. MATERIALS AND METHODS: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. RESULTS: MTX significantly reduced CLIC1-S expression (p=0.016), whereas LFN decreased CLIC1-V (p<0.001). LFN therapy duration also correlated with CLIC1-V (p<0.001). CT decreased CLIC1-S expression (p=0.006). CLIC1-S expression persisted in skin biopsies despite of erythrocyte sedimentation rate (ESR, p=0.018) and C reactive protein (CRP, p=0.0026) normalisation. For PsA, CLIC1-S expression significantly related to MTX (p<0.022). Both CLIC1-S (p<0.001) and CLIC1-V (p=0.007) decreased by biological therapies in RA. CONCLUSION: CLIC1 expression is strongly influenced by the therapy used. Our data strongly support the extensive evaluation of CLIC1 in RA as a potential marker of inflammation and tool to predict therapy response.
34049859 Investigating changes in disease activity as a mediator of cardiovascular risk reduction w 2021 Nov OBJECTIVE: Examine the association of methotrexate (MTX) use with cardiovascular disease (CVD) in rheumatoid arthritis (RA) using marginal structural models (MSM) and determine if CVD risk is mediated through modification of disease activity. METHODS: We identified incident CVD events (coronary artery disease (CAD), stroke, heart failure (HF) hospitalisation, CVD death) within a multicentre, prospective cohort of US Veterans with RA. A 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was collected at regular visits and medication exposures were determined by linking to pharmacy dispensing data. MSMs were used to estimate the treatment effect of MTX on risk of incident CVD, accounting for time-varying confounders between receiving MTX and CVD events. A mediation analysis was performed to estimate the indirect effects of methotrexate on CVD risk through modification of RA disease activity. RESULTS: Among 2044 RA patients (90% male, mean age 63.9 years, baseline DAS28-CRP 3.6), there were 378 incident CVD events. Using MSM, MTX use was associated with a 24% reduced risk of composite CVD events (HR 0.76, 95% CI 0.58 to 0.99) including a 57% reduction in HF hospitalisations (HR 0.43, 95% CI 0.24 to 0.77). Individual associations with CAD, stroke and CVD death were not statistically significant. In mediation analyses, there was no evidence of indirect effects of MTX on CVD risk through disease activity modification (HR 1.03, 95% CI 0.80 to 1.32). CONCLUSIONS: MTX use in RA was associated with a reduced risk of CVD events, particularly HF-related hospitalisations. These associations were not mediated through reductions in RA disease activity, suggesting alternative MTX-related mechanisms may modify CVD risk in this population.
34173901 Selected clinical parameters and changes in cardiac morphology and function assessed by ma 2021 Nov BACKGROUND: The aim of the study was to assess the relationship between the occurrence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and the cardiac magnetic resonance (CMR) changes in people without clinically overt heart disease. METHODS: The study group consisted of 74 people (48.81 ± 11.35 years): 29 patients with RA, 23 patients with AS and 22 people from control group. Blood samples were taken to assess laboratory parameters, disease activity was determined using activity scales, and CMR was performed. RESULTS: It was shown that the factors independently related to higher left ventricular mass index are AS occurrence, human B27 leukocyte antigen occurrence, higher neutrophil gelatinase-associated lipocalin concentration (NGAL) and higher body mass index (BMI). The lower right ventricular ejection fraction is result of an independent effect of RA, AS and higher NGAL. RA presence, methotrexate use, higher rheumatoid factor titer, higher NGAL, older age and higher BMI should be considered independent risk factors for greater left ventricular myocardium water content. RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher C-reactive protein concentration can be independently associated with a higher probability of non-ischemic left ventricular myocardium injury. Larger pericardial fluid volume is result of an independent effect of higher NGAL, higher anti-cyclic citrullinated peptide antibodies titer and higher DAS28 disease activity index. Use of steroids is protective factor against larger volume of pericardial fluid. CONCLUSIONS: RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR. Key Points •RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR.. •The independent risk factors for higher LVEF are AS occurrence, human B27 leukocyte antigen occurrence, higher NGAL concentration and higher BMI.. •RA presence, methotrexate use, higher RF, higher NGAL, older age and higher BMI are independent risk factors for higher LV T2 ratio.. •RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher CRP are independently associated with a higher risk of non-ischemic LV myocardium injury..
33408105 Disease-modifying antirheumatic drugs and organising pneumonia. 2021 Jan 6 Organising pneumonia (OP) in rheumatoid arthritis (RA) may be part of pulmonary manifestation (disease related) or disease-modifying antirheumatic drugs (DMARDs) related. We report a case series of RA patients with DMARDs related OP. A 65-year-old woman developed OP 3 weeks after initiation of methotrexate (MTX). High-resolution CT (HRCT) scan of the thorax revealed bilateral consolidations in the lung bases. She had complete radiological resolution 6 months after corticosteroid therapy with cessation of MTX. The second case was of a 60-year-old woman on MTX with recent addition of leflunomide due to flare of RA. She developed worsening cough 4 months later and HRCT scan revealed consolidation in the left upper lobe with biopsy proven OP. She responded within 6 months of corticosteroid therapy with clinical and radiological resolution. This case series highlights that OP may developed with low-dose MTX (as early as 3 weeks) and leflunomide and the diagnosis requires a high index of suspicion.
34281633 Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparis 2021 Sep OBJECTIVE: The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab as monotherapy were assessed and compared with those of adalimumab in patients with rheumatoid arthritis (RA) who were intolerant to or responded inadequately to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab, and adalimumab in RA patients who are intolerant to or show an inadequate response to MTX. RESULTS: Three RCTs comprising 1,066 patients met the inclusion criteria. Tocilizumab 8 mg monotherapy was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ACR20 response rate. Compared with adalimumab, tocilizumab, and sarilumab as monotherapy showed significantly higher ACR20 response rates. Ranking probability based on SUCRA indicated that tocilizumab 8 mg had the highest probability of being the best choice for achieving ACR20 response rate, followed by sarilumab 200 mg, adalimumab 40 mg, and sirukumab 50 mg. Moreover, the ACR50 response rate showed a similar distribution pattern to that of ACR20. Regarding adverse events, the ranking probability based on SUCRA indicated that sarilumab 200 mg was possibly the safest, followed by adalimumab 40 mg, tocilizumab 8 mg, and sirukumab 50 mg. However, the number of patients who experienced serious adverse events did not differ significantly between these biologics. CONCLUSION: Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance.
33078254 Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retro 2021 May OBJECTIVE: We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL). METHOD: Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653). RESULTS: In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8 mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13-20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05-1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different. CONCLUSIONS: Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA. Key Points • NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease. • Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence. • Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.
33492182 Good response to methotrexate is associated with a decrease in the gene expression of ABCG 2021 Nov OBJECTIVES: Methotrexate (MTX) is used as an anchor drug in the treatment of rheumatoid arthritis (RA), although more than a half of the patients with RA require additional treatments. We designed a prospective study involving two medical centers in Japan to examine the association between the expression of MTX-related genes including a drug transporter ATP-binding cassette sub-family G member 2 (ABCG2) gene and the clinical response to MTX in MTX-naive patients with RA. METHODS: The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. RESULTS: Based on the clinical response at 12 weeks after the initiation of MTX, 24 patients were classified into good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of the baseline gene expression levels to predict the EULAR good response at week 12 showed a significant association with ABCG2 expression alone. Furthermore, the rate of baseline expression of ABCG2 mRNA above the cut-off value determined using a receiver operating characteristic curve was higher in good responders than in non-good responders (p = .012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% vs. +41% from baseline, respectively; p = .011). The ABCG2 expression level did not correlate with DAS28 at baseline or week 12. CONCLUSIONS: Our study revealed that good response to MTX is associated with a decrease in the expression of ABCG2 in patients with RA.
34511571 Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthr 2022 Apr 1 Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.
33911135 Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expa 2021 Apr 28 Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied. Blood samples were collected: before MTX, ≥ 4 weeks on stable MTX dose (prevaccination), and 7 days postvaccination (MTX group), and pre- and 7 days postvaccination (0DMARD and HC). Phenotypes of B- and T cell subsets were determined using flow cytometry. Serotype-specific IgG were quantified using multiplex bead assay, pre- and 4-6 weeks postvaccination. Concentrations of plasmablasts and switched memory B cells increased after PCV in HC (both p = 0.03) and the 0DMARD group (p = 0.01 and p = 0.02), but not in the MTX group. Postimmunization plasmablasts were lower in MTX group, compared to the 0DMARD group and HC (p = 0.002 and p < 0.001). Th17 cells decreased after MTX start (p = 0.02), and increased in HC after immunization (p = 0.01). Postimmunization plasmablasts correlated with mean antibody response ratio in all RA patients (R = 0.57, p = 0.035). Methotrexate reduced Th17 cells and blocked activation of plasmablasts and switched memory B cells following polysaccharide-protein conjugate antigen challenge in RA.
33238812 Primary cutaneous diffuse large B-cell lymphoma, leg type, in a patient with rheumatoid ar 2021 Jul An 84-year-old woman, who was diagnosed with rheumatoid arthritis (RA) and was treated with methotrexate and, subsequently, etanercept (ETN) for 6 years, presented with rapidly progressing painful cutaneous mass on the right medial malleolus. The patient was eventually diagnosed with primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT). ETN therapy was promptly discontinued expecting spontaneous regression of the lymphoma, which was thought to have developed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders. However, no tumour regression was noted. Chemoimmunotherapy was subsequently initiated, which resulted in partial remission. PCLBCL-LT rarely occurs in patients with RA. Here, we report the first case of PCLBCL-LT that developed in a patient with RA receiving ETN therapy.
33847489 NIR-Responsive Spatiotemporally Controlled Cyanobacteria Micro-Nanodevice for Intensity-Mo 2021 Apr 28 The expression of hypoxia-inducible factor-1α (HIF-1α) is upregulated in hypoxic environments at the lesions of rheumatoid arthritis (RA), which promoted the polarization of proinflammatory M1 macrophages and inhibited the differentiation of anti-inflammatory M2 to deteriorate synovial inflammation. Since oxygen scarcity at the joints causes an imbalance of macrophages M1 and M2, herein, we designed a cyanobacteria micro-nanodevice that can be spatiotemporally controlled in vivo to continuously producing oxygen in the RA joints for the downregulation of the expression of HIF-1α, thereby reducing the amounts of M1 macrophages and inducing the polarization of M2 macrophages for chemically sensitized RA treatment. The forthputting of temperature-sensitive hydrogel guaranteed the safety of cyanobacteria micro-nanodevice in vivo. Furthermore, the oxygen produced by cyanobacteria micro-nanodevice in a sustained manner enhanced the therapeutic effect of the antirheumatic drug methotrexate (MTX) and discouraged inflammation and bone erosion at RA. This study provided a new approach for the RA treatment of spatiotemporal-controlled release of oxygen in vitro.
34763513 Systematic review and meta-analysis on the efficacy of methotrexate in rheumatoid arthriti 2021 Oct BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease dominated by chronic inflammation of the synovium of the joints. Methotrexate (MTX) is the most widely used in the treatment of RA. This study systematically evaluated the clinical efficacy of MTX on RA and provided a theoretical basis for the clinical treatment of RA. METHODS: Four English databases (PubMed, Embase, Medline, and Web of Sciences) were searched for randomized controlled trials (RCTs) on MTX treatment of RA published from the date of establishment of the database to 2021. The Cochrane Handbook 5.0.2 was used to perform risk bias evaluation and Review Manager 5.3 was used to conduct a meta-analysis. RESULTS: A total of eight articles were included. The meta-analysis showed that, compared to the control group, the number of patients with DAS28-ESR ≤2.6 [erythrocyte sedimentation rate (ESR)] in the MTX alone or MTX combined treatment groups was higher, and the incidence of adverse events was also higher. However, there was no significant difference in the level of alanine aminotransferase (ALT) after treatment versus the control group. DISCUSSION: MTX alone or MTX combined treatment can better control the condition of RA patients without causing damage to the patient's blood system or liver and kidney function, but may increase the probability of adverse events.
34313866 Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcome 2021 Dec INTRODUCTION: Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment. The aim of this study was to evaluate abatacept (ABA) effectiveness and safety in patients with RA-ILD. METHODS: RA-ILD patients who started ABA treatment were consecutively enrolled. Chest high-resolution computed tomography (HRCT), clinical, laboratory and respiratory function variables were collected at baseline and after 18 months of ABA treatment. HRCT abnormalities were evaluated using a computer-aided method (CaM). ABA response was established based on the change in the percentage of fibrosis evaluated at HRCT-CaM, dividing patients into "worsened" (progression ≥ 15%), "improved" (reduction ≥ 15%), and "stable" (changes within the 15% range). The multivariate regression model was used to assess the associations between RA characteristics and ABA response. RESULTS: Forty-four patients (81% women, mean age 59.1 ± 8.0, mean disease duration of 7.5 ± 3.1 years) were studied. Five patients (11.4%) showed RA-ILD progression, 32 patients (72.6%) were considered stable, and 7 patients (16.0%) showed an RA-ILD improvement. The proportion of current smokers was significantly different between "worsened" patients, respect to those defined as "improved/stable" (p = 0.01). Current smoking habit (p = 0.005) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in multivariate regression analysis. CONCLUSION: Treatment with ABA is associated with a RA-ILD stability or improvement in the 88.6% of patients. Current smoking habit and concomitant treatment with methotrexate are the modifiable factors associated with RA-ILD worsening. Key Points • Abatacept plays a favourable role in the control of RA-ILD, with a significant worsening in only 11.4% of patients during a 18-month follow-up period. • The predictive variables related to RA-ILD progression during abatacept therapy are the concomitant treatment with methotrexate and current smoking habit.
33790392 Prediction of response of methotrexate in patients with rheumatoid arthritis using serum l 2021 Mar 31 Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30-40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra-performance liquid chromatography-mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.