Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35284559 | The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of rheumatoid arthritis ch | 2022 Feb | BACKGROUND: Based on the ASIC1a/NLRP3 signaling pathway, we explored the specific molecular mechanism of the pyroptosis of rheumatoid arthritis (RA) chondrocytes by the method of nourishing qi, nourishing yin, and dredging collaterals to provide new ideas for the treatment of this disease. METHODS: A total of 50 rats were divided into a normal group, model group, methotrexate group, Yiqi Yangyin Tongluo group, and combined group. Except for the normal control group, the other groups used Freund's complete adjuvant (FCA) to make RA rat model. The arthritis index and ankle joint swelling of rats in each group were recorded. HE staining and ELISA were used to assess the pathology of the ankle joint of each group of rats and the content of IL-1β and IL-18 in rat serum. Furthermore, immunofluorescence and qPCR methods were used to detect the protein and mRNA expression levels of NLRP3, caspase 1, ACS, and ASIC1a in the cartilage tissue of each group of rats. RESULTS: Compared with the normal group, the right hind foot joint of the model group was significantly swollen, the levels of IL-18 and IL-1β in the serum of rats increased significantly, and the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes also increased significantly. Compared with the model group, the degree of ankle joint swelling and IL-18 and IL-1β content in rat serum in each medication group was significantly reduced, and the combined group showed the greatest reduction compared with the other groups. After 8 weeks of treatment, compared with the model group, the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes of each medication group were down-regulated. HE staining found that there were large numbers of infiltrating inflammatory cells and pannus in the joint tissue of the model group, while only a small amount of inflammatory cell infiltration and pannus was seen in the joint tissue of the rats in each treatment group. CONCLUSIONS: The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of RA chondrocytes through the ASIC1a/NLRP3 signaling pathway. | |
| 35203442 | Folate-Targeted Liposomal Formulations Improve Effects of Methotrexate in Murine Collagen- | 2022 Jan 21 | Methotrexate (MTX) is first-line therapy for the treatment of rheumatoid arthritis (RA), however, its use may be limited by side effects notably post-injection malaise. When patients are intolerant or become unresponsive, second-line or antibody therapy may be indicated. A folate-targeted liposomal formulation of MTX (FL-MTX) is tropic to arthritic paws and prevents the onset of collagen-induced arthritis (CIA) in the mouse. We optimized the drug-to-lipid molar ratio to 0.15 and demonstrated the therapeutic efficacy of this form at 2 mg/kg MTX intraperitoneal (i.p.) twice a week. These improved liposomes were present in inflamed joints in proportion to the degree of swelling of the paw and bone remodeling activity. FL-MTX had lower hepatic and renal elimination of MTX than the free substance. FL-MTX provided equivalent results when given i.p. or subcutaneous (s.c.) and FL-MTX 2 mg/kg (drug/lipid 0.15), twice weekly, was similar to or more effective than 35 mg/kg MTX (same route and schedule) in reducing the incidence and swelling in the murine CIA model. These results suggest that FL-MTX is a more potent nanotherapeutic formulation than free MTX treatment. Its potential benefits for patients may include reduced frequency of treatment and lower overall doses for a given response. | |
| 35458007 | Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment | 2022 Apr 11 | Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery. | |
| 35329893 | Herb-Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplem | 2022 Mar 12 | Many people worldwide use plant preparations for medicinal purposes. Even in industrialized regions, such as Europe, where conventional therapies are accessible for the majority of patients, there is a growing interest in and usage of phytomedicine. Plant preparations are not only used as alternative treatment, but also combined with conventional drugs. These combinations deserve careful contemplation, as the complex mixtures of bioactive substances in plants show a potential for interactions. Induction of CYP enzymes and pGP by St John's wort may be the most famous example, but there is much more to consider. In this review, we shed light on what is known about the interactions between botanicals and drugs, in order to make practitioners aware of potential drug-related problems. The main focus of the article is the treatment of inflammatory diseases, accompanied by plant preparations used in Europe. Several of the drugs we discuss here, as basal medication in chronic inflammatory diseases (e.g., methotrexate, janus kinase inhibitors), are also used as oral tumor therapeutics. | |
| 34854263 | Journal Club Review of "What Is the Persistence to Methotrexate in Rheumatoid Arthritis, a | 2022 Mar | OBJECTIVE: The objectives of this study were to assess the 1-year persistence to methotrexate (MTX) initiated as the first ever conventional synthetic disease-modifying antirheumatic drug in new-onset rheumatoid arthritis (RA) and to investigate the marginal gains and robustness of the results by increasing the number and nature of covariates and by using data-driven, instead of hypothesis-based, methods to predict this persistence. METHODS: Through the Swedish Rheumatology Quality Register, linked to other data sources, we identified a cohort of 5475 patients with new-onset RA in 2006-2016 who were starting MTX monotherapy as their first disease-modifying antirheumatic drug. Data on phenotype at diagnosis and demographics were combined with increasingly detailed data on medical disease history and medication use in four increasingly complex data sets (48-4162 covariates). We performed manual model building using logistic regression. We also performed five different machine learning (ML) methods and combined the ML results into an ensemble model. We calculated the area under the receiver operating characteristic curve (AUROC) and made calibration plots. We trained on 90% of the data, and tested the models on a holdout data set. RESULTS: Of the 5475 patients, 3834 (70%) remained on MTX monotherapy 1 year after treatment start. Clinical RA disease activity and baseline characteristics were most strongly associated with the outcome. The best manual model had an AUROC of 0.66 (95% confidence interval [CI] 0.60-0.71). For the ML methods, Lasso regression performed best (AUROC = 0.67; 95% CI 0.62-0.71). CONCLUSION: Approximately two thirds of patients with early RA who start MTX remain on this therapy 1 year later. Predicting this persistence remains a challenge, whether using hypothesis-based or ML models, and may yet require additional types of data. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acr2.11266 Westerlind H, Maciejewski M, Frisell T, Jelinsky SA, Ziemek D, Askling J. What is the persistence to methotrexate in rheumatoid arthritis, and does machine learning outperform hypothesis-based approaches to its prediction? ACR Open Rheumatol 2021;3:457-463. | |
| 34535869 | The effectiveness of tocilizumab in treating refractory adult-onset Still's disease with d | 2022 Feb | OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration. METHODS: This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method. RESULTS: Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28 < 2.6) at weeks 12, 24, 36, and 48, respectively, among articular subtype patients. The systemic activity scores and inflammatory parameters were significantly decreased after 12-week TCZ therapy, and TCZ could significantly reduce corticosteroid dose in AOSD patients. Multivariate analysis reveals that baseline IL-18 level is a significant predictor of poor therapeutic response at week 24 (odds ratio 7.86, p < 0.05). CONCLUSION: AOSD patients refractory to high-dose corticosteroids and methotrexate may respond well to TCZ treatment with a steroid-sparing effect and an acceptable safety. A high baseline IL-18 level may be a predictor of poor therapeutic response. Key Points • Tocilizumab may be effective and well-tolerated in refractory AOSD patients regardless of disease subtypes. • High plasma levels of IL-18 may predict poor response to tocilizumab in AOSD patients. | |
| 35490916 | Methotrexate promotes recovery of arthritis-induced alveolar bone loss and modifies the co | 2022 Apr 28 | OBJECTIVES: The impact of rheumatoid arthritis (RA) on the shaping of the oral and gut microbiome raises the question of whether and how RA treatment modifies microbial communities. We examined changes in the oral and gut microbiota in a mouse model of antigen-induced arthritis (AIA) treated or not with methotrexate (MTX). METHODS: Maxillae and stools were evaluated by the MiSeq platform of the V4 region of the 16S rRNA gene. Alveolar bone parameters were analysed by micro-computed tomography. Moreover, arthritis-induced changes in hyperalgesia and oedema were assessed, along with the impact on periodontal bone health. RESULTS: Microbial communities in MTX-treated AIA mice revealed distinct clusters compared to the control and AIA groups. Overall, MTX impacted the richness and variability of microorganisms in the oral-gut axis microbiome at the phylum level. Regarding the oral microbiome, while in the control group the most dominant phylum was Firmicutes, in the AIA group there was a shift towards the predominance of Campilobacteriota and Bacteroidetes associated with the disease. MTX treatment led to greater dominance of the health-associated phylum Proteobacteria. In the gut microbiome, AIA induction resulted in increased abundance of the Verrucomicrobiota phylum, and MTX treatment restored its levels compared to control. Importantly, the MTX-treated AIA animals had significantly less periodontal bone loss, as well as decreased hyperalgesia and joint oedema compared to the AIA animals. CONCLUSION: Data suggest the benefit of MTX treatment in protecting alveolar bone, in addition to providing new insights on the drug-microbiome interaction in the course of RA. | |
| 35641124 | Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) | 2022 May 31 | OBJECTIVE: This phase 2a randomised, double blind, placebo controlled, parallel group study evaluated the safety and efficacy of a first-in-class drug candidate ABX464 (obefazimod, 50 mg and 100 mg per day), which upregulates the biogenesis of the mRNA inhibitor micro-RNA (miR)-124, in combination with methotrexate (MTX) in 60 patients (1:1:1 ratio) with moderate-to-severe active rheumatoid arthritis (RA) who have inadequate response to MTX or/and to an anti-tumour necrosis factor alpha (TNFα) therapy. METHODS: The primary end point was the safety of ABX464; efficacy endpoints included the proportion of patients achieving American College of Rheumatology (ACR)20/50/70 responses, disease activity scores (DAS) 28, simplified disease activity score, clinical disease activity score), European League Against Rheumatism response, DAS28 low disease activity or remission. RESULTS: ABX464 50 mg was safe and well tolerated. Two serious adverse events were reported (one on placebo group and one on ABX464 100 mg). Eleven patients were withdrawn for AEs (9 patients on 100 mg, 1 on 50 mg and 1 on placebo). Drug discontinuation was mainly due to gastrointestinal disorders. No cases of opportunistic infection, no malignancies and no death were reported. Compared with placebo, ABX464 50 mg showed significantly higher proportions of patients achieving ACR20 and ACR50 responses at week 12. DAS28-C reactive protein (CRP) and DAS28-erythrocyte sedimentation rate decreased significantly and rates of categorical DAS28-CRP response or CDAI remission increased significantly on ABX464 at week 12. A significant upregulation of miR-124 was observed in blood for every patient dosed with ABX464. CONCLUSION: ABX464 50 mg was safe, well tolerated and showed a promising efficacy. Mild-to-moderate gastrointestinal AEs led to a high drop-out rate of patients on ABX464 100 mg, which may not be a relevant dose to use. These findings warrant exploration of ABX464 at 50 mg per day or less for treating patients with RA. TRIAL REGISTRATION NAME: Phase IIa randomised, double blind, placebo controlled, parallel group, multiple dose study on ABX464 in combination with MTX, in patients with moderate to severe active RA who have inadequate response to MTX or/and to an anti- TNFα therapy or intolerance to anti-TNFα therapy.EUDRACT number: 2018-004677-27 TRIAL REGISTRATION NUMBER: NCT03813199. | |
| 35115930 | The Effect and Safety of Iguratimod Combined With Methotrexate on Rheumatoid Arthritis: A | 2021 | Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with inflammatory synovitis. Iguratimod (IGU) combined with methotrexate (MTX) therapy may have better efficacy and safety. Methods: First, we searched randomized controlled trials (RCTs) of IGU + MTX in the treatment of RA through literature databases (such as PubMed, Corkland Library, CNKI, etc.) and then conducted RCT quality assessment and data extraction. Finally, we used RevMan 5.3 for meta-analysis, STATA 15.0 for publication bias assessment, and GRADE tool for the evidence quality assessment of primary outcomes. This systematic review and meta-analysis were registered in PROSPERO (CRD42021220780). Results: This systematic review and meta-analysis included 31 RCTs involving 2,776 patients. Compared with MTX alone, the ACR20, ACR50, and ACR70 of IGU + MTX are higher, while DAS28 is lower [ACR20: (RR 1.55, 95% CI 1.14-2.13, p = 0.006); ACR50: (RR 2.04, 95% CI 1.57-2.65, p < 0.00001); ACR70: (RR 2.19, 95% CI 1.44-3.34, p = 0.00003); DAS28: (weighted mean difference (WMD) -1.65, 95% CI -2.39 to -0.91, p < 0.0001)]. Compared with MTX + leflunomide, IGU + MTX has no significant difference in improving ACR20, ACR50, ACR70, but IGU + MTX improves DAS28 more significantly [ACR20: (RR 1.09, 95% CI 0.79-1.89, p = 0.59); ACR50: (RR 1.07, 95% CI 0.64-1.78, p = 0.81); ACR70: (RR 1.17, 95% CI 0.44-3.10, p = 0.76); DAS28: (WMD -0.40, 95% CI -0.42 to -0.38, p < 0.0001)]. Compared with the MTX + tripterygium subgroup and MTX-only subgroup, the incidence of adverse events of the IGU + MTX group is of no statistical significance [MTX only: (RR 0.99, 95% CI 0.87-1.13, p = 0.90); MTX + Tripterygium: (RR 0.73, 95% CI 0.29-1.85, p = 0.50)]. However, compared with MTX + leflunomide, the incidence of adverse events in the IGU + MTX group was lower (RR 0.74, 95% CI 0.62-0.88, p = 0.0009). The quality of ACR70 was high; the quality of adverse events and ACR50 test was moderate. Conclusion: Compared with conventional therapy, IGU + MTX may be a safer and more effective therapy for RA patients. When the intervention method is (IGU 25Â mg Bid, MTX 10-25Â mg once a week), and the intervention lasts for at least 12Â weeks, the curative effect may be achieved without obvious adverse events. | |
| 35452005 | Bone Scan With SPECT/CT Demonstrated C1 to C2 Involvement in Rheumatic Arthritis. | 2022 Apr 22 | An 80-year-old man was treated with rituximab for active rheumatoid arthritis until 2019, now controlled with Salazopyrin, prednisolone, methotrexate, and folic acid. However, laboratory data showed elevated C-reactive protein and erythrocyte sedimentation rate. Whole-body bone scan showed bony and joint destruction to the upper cervical vertebra (C spine), bilateral shoulders, wrists, finger joints, ankles, and left knee. SPECT/CT localized the upper C spine uptake to the C1/C2 joint and adjacent C1 and C2 with C1/C2 subluxation. C spine CT showed vertical atlantoaxial subluxation and bony erosions. | |
| 35084325 | Enhanced expression of mRNA for transforming growth factor β activated kinase 1 in CD34+ | 2022 Jan 27 | OBJECTIVES: Transforming growth factor β activated kinase 1 (TAK1) has been found to mediate maladaptive tumour necrosis factor (TNF) signalling, leading to hyperactive downstream nuclear factor Kappa β (NF-κB) signalling. We explored the expression of TAK1 mRNA in bone marrow CD34+ cells in rheumatoid arthritis (RA) to delineate the mechanism for their abnormal response to TNF-α and differentiate into fibroblast-like cells. METHODS: CD34+ cells were purified from bone marrow samples obtained from 47 RA patients and 27 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The expression of mRNAs for TAK1 and NFκB1 was examined by quantitative RT-PCR. RESULTS: TAK1 mRNA expression in bone marrow CD34+ cells was significantly higher in RA than in OA (TAK1/β-actin: [11.980 ± 2.380] x 10-3 and [5.593±1.307] x 10-3 [mean ± SEM], respectively; p=0.0238). TAk1 mRNA expression was not different depending on the type of operated joints or on the severity type of RA. Nor was it correlated with serum CRP or rheumatoid factor or with administration of methotrexate, other conventional synthetic disease-modifying anti-rheumatic drugs or oral glucocorticoid. TAK1 mRNA expression was significantly correlated with NFκB1 mRNA expression in RA bone marrow CD34+ cells. CONCLUSIONS: These results indicate that TAK1 mRNA expression is enhanced in bone marrow CD34+ cells independently of the clinimetrics or treatment in RA. It is also suggested that the upregulation of TAK1 mRNA expression might lead to the enhanced expression of NFκB1 mRNA in bone marrow CD34+ cells, but possibly not vice versa, resulting in their abnormal response to TNF-α. | |
| 35467748 | A Case of Rheumatoid Arthritis With Bilateral Shoulder Bursitis Accompanied by Gas Image. | 2022 Apr 25 | We experienced a case of bilateral shoulder bursitis with gas images in a rheumatoid arthritis (RA) patient. A 60-year-old man with RA had been treated with weekly methotrexate (MTX) 10 mg and daily prednisolone (PSL) 10 mg for 7 months. Generalized pain, especially in the bilateral shoulder joints developed and exacerbated daily with increased CRP level. Despite the initiation of biweekly Sarilumab 200 mg, joint symptoms and CRP level continued to worsen. Computed tomography (CT) scan to determine the cause of severe shoulder inflammation revealed low absorption areas with contrast effects at the margins around the bilateral shoulder joints, accompanied by internal gas images. In addition, magnetic resonance imaging (MRI) demonstrated subacromial bursae and coracoid bursae, and bursitis leading to the suspicion of abscess formation depending on the presence of gas image. In spite of antimicrobial therapy, arthralgia did not improve and a CT-guided arthrocentesis of the left shoulder joint resulted in negative findings of infection in culture and pathological examinations. Switching treatment to intensive anti-inflammatory therapy with high-dose steroids and Etanercept finally improved symptom and CRP level associated with the reduction of low absorption areas and disappearance of gas images at bilateral shoulder joints. Our case indicated that bursitis with gas image in RA patients involves unusual pathophysiology and requires intensive anti-rheumatic treatment. | |
| 35256384 | Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for | 2022 Jan 24 | BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored. | |
| 35232809 | Impact of Tofacitinib on Components of the ACR Response Criteria: Post Hoc Analysis of Pha | 2022 Jun | OBJECTIVE: To evaluate the effect of tofacitinib (TOF) on American College of Rheumatology (ACR) response criteria components in patients with rheumatoid arthritis (RA). METHODS: This post hoc analysis pooled data from RA phase III randomized controlled trials (RCTs) assessing TOF 5 or 10 mg BID, adalimumab (ADA), or placebo, with conventional synthetic disease-modifying antirheumatic drugs, and a phase IIIb/IV RCT assessing TOF 5 mg BID monotherapy, TOF 5 mg BID with methotrexate (MTX), or ADA with MTX. Outcomes included proportions of patients achieving ACR20/50/70 responses and ≥ 20/50/70% improvement rates in ACR components at week 2 and months 1, 3, and 6; and mean percent improvement in ACR components and Clinical or Simplified Disease Activity Index (CDAI or SDAI) low disease activity or remission rates, at month 3, for ACR20/50/70 responders. RESULTS: Across treatment groups, ≥ 20/50/70% improvement rates were numerically higher for most physician- vs patient-reported measures. In phase III RCTs, at earlier timepoints, ≥ 50/70% improvements in patient global assessment of disease activity, pain, and physician global assessment were similar. Among ACR20 responders receiving TOF, mean percent improvements for tender and swollen joint counts were > 70% at month 3. CDAI/SDAI remission was achieved at month 3 by 27.8-45.0% of ACR70 responders receiving TOF. CONCLUSION: Among ACR20 responders treated with TOF, physician-reported components particularly exceeded 20% response improvement. At month 3, disease state generally did not corroborate ACR70 response criteria. Divergences between physician- and patient-reported measures highlight the importance of identifying appropriate patient-reported outcome targets to manage RA symptoms in clinical practice. (ClinicalTrials.gov: NCT00847613/NCT00856544/NCT00853385/NCT02187055). | |
| 35148758 | Methotrexate-loaded nanoparticles ameliorate experimental model of autoimmune arthritis by | 2022 Feb 11 | BACKGROUND: Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important. METHODS: To investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against experimental model of RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry. RESULTS: MTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Number of CD4 + IL-17 + cells decreased whereas the number of CD4 + CD25 + Foxp3 + cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19 + CD25 + Foxp3 + regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice. CONCLUSION: The results suggest that MTX-loaded NPs have therapeutic potential for RA. | |
| 29494057 | Cyclosporine. | 2022 Jan | Cyclosporine is an immunosuppressive agent used to treat organ rejection post-transplant. It also has use in certain other autoimmune diseases, treatment of organ rejection in kidney, liver, and heart allogeneic transplants, rheumatoid arthritis when the condition has not adequately responded to methotrexate. Also, it is a second-line agent for ALS and graft vs. host disease. It also has other FDA and non-FDA-approved indications. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cyclosporine, pertinent for interprofessional team members in treating conditions where cyclosporine is indicated. | |
| 35156626 | Identifying physician-perceived barriers to a pragmatic treatment trial in rheumatoid arth | 2022 Feb 14 | OBJECTIVE: The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a rheumatoid arthritis (RA) pragmatic trial of anti-tumor necrosis factor (TNF) biologic versus non-TNF biologic/Janus-Kinase inhibitor initiation after an inadequate response to methotrexate. METHODS: Semistructured telephone interviews were conducted with 26 rheumatologists in March 2019. An exploratory thematic analysis approach was used to analyze the interview data. RESULTS: Physician perceived patient barriers to the implementation of an RA pragmatic trial. This theme covers three subthemes: (1) patients' personal barriers, (2) patients' treatment-related factors, and (3) trial-related factors (eg, patient recruitment, side effects, mode of use, etc). Physicians perceived clinic barriers interfered with the pragmatic trial enrollment from the clinic or the healthcare system perspective. This theme covered four subthemes: (1) clinic-related factors, (2) patient-related factors, (3) research personnel, and (4) facilitators (positive factors of the clinic). CONCLUSION: Our results from the inductive thematic analysis will help researchers understand the key patient and clinic/system factors/barriers that may influence pragmatic RA trial implementation. The themes suggest there are factors that can be modified (eg, coordinator effort needed, effective patient recruitment during clinic visits, provider engagement) and challenges to overcome (patient insurance status, busy clinic flow, and space issues including limited number of patient rooms). In summary, these themes provide a basis for our and other research teams to develop clinic-centered and patientcentered strategies to implement a pragmatic RA trial. | |
| 35652244 | Combined conventional synthetic disease modifying therapy vs infliximab for rheumatoid art | 2022 Jun 2 | Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from rheumatoid arthritis (RA) patients in the Swedish Rheumatology Quality Register (SRQ), between 2006 and 2020, we emulated the protocol of the Swedish Farmacotherapy trial (SWEFOT) and compared the results. SWEFOT was a pragmatic trial nested in SRQ, between 2002 and 2005, where methotrexate insufficient responders were randomized to receive additional infliximab or sulfasalazine + hydroxychloroquine. RA patients initiating infliximab (N=313) or sulfasalazine + hydroxychloroquine (N=196) after methotrexate were identified in SRQ and the Prescribed Drugs Register, mimicking the SWEFOT eligibility criteria. The primary outcome was the proportion of EULAR (European Alliance of Associations for Rheumatology) good responders at nine months, classifying patients who discontinued treatment as "non-responders". Through sensitivity analyses, we assessed the impact of relaxing eligibility criteria. The observed proportions reaching EULAR good response were close to those reported in SWEFOT: 39% (vs. 39% in SWEFOT) for infliximab and 28% (vs. 25%) for sulfasalazine + hydroxychloroquine. The crude observed response ratio was 1.39 (95% CI: 1.04 to 1.86), increasing to 1.48 (0.98 to 2.24) after confounding adjustment, compared to 1.59 (1.10 to 2.30) in SWEFOT. Results remained close to SWEFOT when relaxing eligibility criteria until allowing prior DMARD use which reduced the observed difference between treatments. By applying a pre-specified trial emulation protocol to observational clinical registry data, we could replicate the results of SWEFOT, favouring infliximab over sulfasalazine + hydroxychloroquine combination therapy at nine months. | |
| 34998078 | The effects of autoimmune rheumatic-related diseases on male reproductive health: A system | 2022 Mar | Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated fertility problems in females, data on males-related fertility are scarce, which explains the lack of guidance. The main objective of this systematic review was to evaluate the reproductive health in males with ARRDs. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until September 16, 2021, and tackling the effects of ARRDs and/or ARRDs treatments on male fertility and/or pregnancy outcomes, were included. A total of twenty-five studies met the inclusion criteria. They were published between 1981 and 2018. The studied ARRDs were spondyloarthritis (n = 9), systematic lupus erythematosus (SLE, n = 6), Behcet disease (BD, n = 5), rheumatoid arthritis (RA, n = 5), antiphospholipid syndrome (n = 1), and dermatomyositis (n = 1). The most reported effects of ARRDs on fertility are i) high levels of reproductive hormones, mainly in RA and SLE; ii) impaired semen quality in SLE, spondyloarthritis, and BD; and iii) higher rate of varicocele in BD and spondyloarthritis. Regarding the treatments effects, i) conventional synthetic disease-modifying anti-rheumatic drugs (e.g.; methotrexate and salazopyrine) increase testosterone level, ii) cyclophosphamide impairs fertility, iii) anti-tumor necrosis factor agents are associated with improvement in semen quality, and iv) no increased number of miscarriages or congenital abnormalities in children fathered by BD was reported. To conclude, both ARRDs and their treatments alter fertility in males with ARRDs. In practice, in addition to the conventional semen analysis, screening for infertility seems legitimate in males with ARRDs. | |
| 35110573 | Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rhe | 2022 Feb 2 | Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations. |