Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 34970879 | [Effect of electroacupuncture on autophagy in synovial tissues of rheumatoid arthritis rat | 2021 Dec 25 | OBJECTIVE: To observe the effects of electroacupuncture (EA) on autophagosomes, unc-51-like autophage activating kinase 1 (ULK1), Beclin1, and microtubule-associated protein light chain 3 (LC3) expression, and synoviocyte ultrastructure in the synovial tissues of rheumatoid arthritis (RA) rats, and to explore the mechanism of EA in regulating the proliferation of synoviocytes via the autophagy pathway. METHODS: The SD rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group, and an EA group, with 6 rats in each group. Following RA modeling with Freund's complete adjuvant, rats in the MTX group were treated with intragastric administration of 0.35 mg/kg MTX, twice a week, for 4 weeks, while those in the EA group received 20-min EA stimulation at "Zusanli" (ST36) and "Guanyuan" (CV4), once per day, for 4 weeks, with an interval of one day between weeks. The rat left hind toe volume was measured using the toe volume measuring instrument. HE staining was conducted for detecting the morphology of rat synovial tissues, followed by the observation of autophagosomes under the transmission electron microscope. The levels of serum interleukin (IL)-1 and tumor necrosis factor (TNF)-α were assayed by ELISA, and the protein expression levels of ULK1, Beclin1, and LC3 were detected by Western blot. RESULTS: Compared with the normal group, the left hind toe volume of the model group increased significantly (P<0.01), while serum IL-1 and TNF-α (P<0.01), synovial ULK1, Beclin1, and LC3 protein expression (P<0.01, P<0.05) up-regulated. HE stain and electron microscope showed obvious synovial hyperplasia, and doublemembrane autophagosomes scattering in the synoviocytes. The comparison with the model group showed that MTX and EA remarkably decreased the left hind toe volume (P<0.01), serum IL-1 and TNF-α (P<0.01), down-regulated the protein expression levels of ULK1 and LC3 in synovial tissues (P<0.05, P<0.01), and inhibited the synovial hyperplasia, with no obvious autophagosomes observed in the synoviocytes. The protein expression of ULK1 in the EA group was significantly lower than that in the MTX group (P<0.01). CONCLUSION: EA alleviates the joint swelling and synoviocyte injury of RA rats possibly by regulating the expression of ULK1, LC3, and Beclin1 and inhibiting the synoviocyte autophagy and proliferation. | |
| 33794855 | Assessing the risk of rapid radiographic progression in Hungarian rheumatoid arthritis pat | 2021 Apr 2 | BACKGROUND: The outcome of rheumatoid arthritis (RA) should be determined early. Rapid radiological progression (RRP) is > or = 5 units increase according to the van der Heijde-Sharp score within a year. The risk of RRP can be estimated by a matrix model using non-radiographic indicators, such as C-reactive protein (CRP), rheumatoid factor (RF) and swollen joint count (SJC). PATIENTS AND METHODS: A non-interventional, cross-sectional, retrospective study was conducted in eleven Hungarian arthritis centres. We assessed RRP risk in biologic-naïve RA patients with the prevalence of high RRP risk as primary endpoint. RRP was calculated according to this matrix model. As a secondary endpoint, we compared RRP in methotrexate (MTX) responders vs non-responders. RESULTS: We analyzed data from 1356 patients. Mean CRP was 17.7 mg/l, RF was 139.3 IU/ml, mean 28-joint disease activity score (DAS28) was 5.00 and mean SJC was 6.56. Altogether 18.2% of patients had high risk (≥40%) of RRP. RA patients with high RRP risk of RRP (n = 247) had significantly lower age compared to those with RRP < 40% (n = 1109). MTX non-response (OR: 16.84), male gender (OR: 1.67), erosions at baseline (OR: 1.50) and ACPA seropositivity (OR: 2.18) were independent predictors of high-risk RRP. Male gender (OR: 5.20), ACPA seropositivity (OR: 4.67) and erosions (OR: 7.98) were independent predictors of high RRP risk in MTX responders. CONCLUSIONS: In this Hungarian study, high RRP risk occurred in 18% of RA patients. These patients differ from others in various parameters. RRP was associated with non-response to MTX. | |
| 33547118 | Delayed diagnosis of rheumatoid arthritis in an elderly patient presenting with weakness a | 2021 Feb 5 | We describe the case of an 81-year-old man who presented with unspecific symptoms of desolation and general weakness, which led to a delayed diagnosis of rheumatoid arthritis (RA). The patient had not received any previous treatment as he had not been in contact with medical services for several years prior to hospital admission. This enabled advanced disease manifestations to develop, including peripheral neuropathy with distal paraparesis, lethargy and weight loss. These signs and symptoms were later recognised as extra-articular manifestations of RA and classical features of RA were less pronounced. Following extensive diagnostic testing ruling out other possible causes for the presenting symptoms, an anti-inflammatory therapy with oral glucocorticoids and methotrexate was started. | |
| 34802085 | Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review. | 2022 Feb | PURPOSE: To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. METHODS: A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors' departments were examined. RESULTS: Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin's lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to "bull's eye" maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. CONCLUSION: The level of evidence for most of the drug reactions described herein is restricted to the "likely" or "possible" rather than to the "certain" category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient. | |
| 31451091 | High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Man | 2021 Jun | BACKGROUND: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. OBJECTIVE: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. METHODS: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. RESULTS: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). CONCLUSION: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated. | |
| 32819263 | Tofacitinib-induced Ramsay- Hunt Syndrome in a Patient with Rheumatoid Arthritis. | 2021 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint and systemic involvement. Tofacitinib is a JAK- inhibitor that is an effective agent in the treatment of active RA. Varicella zoster virus(VZV) reactivation is among the most important adverse effects of tofacitinib. Ramsay-Hunt syndrome(RHS) is a rare clinical condition that develops as a result of VZV reactivation and progresses with hearing loss, dizziness, and facial nerve paralysis. OBJECTIVE: To present a case of Ramsay-Hunt syndrome due to varicella zoster reactivation in a RA patient using tofacitinib. CASE REPORT: A 63-year-old female RA patient under tofacitinib treatment was admitted to the rheumatology outpatient clinic due to widespread skin rashes on her face and ear, and hearing loss. On inspection widespread erythematous, vesicular rashes on the left side of the face, lips, around the eye and in the ear, and mild facial paralysis on the left side were detected. On laboratory investigations, acute phase reactants were increased. Serological study for specific antibodies against varicella zoster virus showed higher titers. Dermatology and ear nose throat specialist consultations were performed, and varicella zoster lesions on the left inner ear, face, and mild facial paresis were considered. According to clinical and laboratory findings, the patient was diagnosed with RHS triggered by tofacitinib. Tofacitinib and methotrexate were discontinued, and intravenous acyclovir was started. On the control examination, the patient's skin lesions and facial nerve paralysis regressed. CONCLUSION: Herein, we reported the fırst case of tofacitinib-induced RHS in a patient with RA. This may be another side effect of biologic treatment. New studies are needed on this subject. | |
| 33538619 | Consideration of differences in drug usage between young-onset and elderly-onset rheumatoi | 2021 Nov | OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. METHODS: Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). RESULTS: There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. CONCLUSION: Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA. | |
| 33463632 | SPECT imaging and highly efficient therapy of rheumatoid arthritis based on hyperbranched | 2021 Mar 10 | Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Although significant progress has been made in clinical treatment, joint inflammation may continue or worsen, and may even progress to the end-stage that requires joint replacement. Traditional therapy using methotrexate (MTX) would cause serious off-target systemic toxicities. Therefore, it is crucial to effectively and specifically deliver MTX to targeted inflamed joints to decrease its adverse systemic toxicities and improve its therapeutic index. Herein, we develop multifunctional nanocarriers for diagnostic radioisotope (99mTc) labeling and therapeutic targeted drug (MTX) delivery by using PEGylated hyperbranched semiconducting polymer nanoparticles (HSP-PEG-NPs) as carriers. Upon intravenous administration, the nanoparticles can extravasate through the turbulent blood-joint barrier and access the inflamed joints. In vivo SPECT/CT imaging shows high accumulation in the inflamed joints of mice with RA after intravenous injection of HSP-PEG-NPs with 99mTc labeling (99mTc-HSP-PEG). In vivo therapeutic evaluations suggest that MTX@HSP-PEG-NPs significantly alleviate RA with a high therapeutic index and relatively low adverse systemic toxicities in comparison with free MTX at the same dose. Our study shows that HSP-PEG-NPs could serve as multifunctional vehicles to deliver radioisotopes for in vivo imaging, and MTX for RA treatment, highlighting the innovative development of the nanoparticle-based RA treatment strategy for clinical applications. | |
| 33185166 | Predictors of Cardiovascular Affection in Patients with Active Rheumatoid Arthritis: Secon | 2021 | OBJECTIVE: This is a secondary analysis of a randomized controlled trial that aimed to assess subclinical atherosclerosis in patients with rheumatoid arthritis (RA) by measuring carotid artery intima-media thickness (CIMT) and correlating it with disease activity and inflammatory markers (including levels of matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9 (MMP-9)) and to detect the effectiveness of agents that inhibit matrix metalloproteinases (MMPs) as doxycycline in RA therapy. METHODS: One hundred and sixty RA patients were assigned in a randomized clinical trial (clinicaltrial. gov NCT03194204). Disease activity score 28(DAS28), laboratory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MMP-3, and MMP-9 were evaluated and mean CIMT was measured. Subjects were allocated randomly into one of two treatment arms, either methotrexate (MTX) alone or MTX with doxycycline 200mg per day orally. Follow up ESR, CRP, DAS28, MMP-3, and MMP-9 levels were re-evaluated after 3 months. RESULTS: There were positive significant correlations between CIMT and disease duration (r = 0.461, p = 0.001), age (r=0.459, p= 0.001), DAS28 score (r= 0.547, p = 0.001), ESR (r =0.413, p = 0.001), CRP (r = 0.281, p = 0.001), MMP-3 (r = 0.476, p = 0.001), and MMP-9 (r = 0.593, p =0.001). Patients treated with MTX and doxycycline showed lower levels of DAS28, ESR, CRP, MMP-3, and MMP-9 and this was statistically significant. CONCLUSION: CIMT seems to be the ultimate method to screen for subclinical atherosclerosis in RA patients. MMP-3 and 9 play a key role in both RA synovitis and cardiovascular changes, making them important therapeutic targets, especially with safe and cost-effective agents like doxycycline. This clinical trial was carried out in Assiut University Hospital (AUH), Assiut, Egypt (Clinical Trial Registration No. clinicaltrial.gov NCT03194204). | |
| 33719841 | Discrepancy between clinical and ultrasound remissions in rheumatoid arthritis: a multicen | 2021 Nov | Objectives: Using multicentre ultrasound (US) cohort data among patients with rheumatoid arthritis (RA), we aimed to identify baseline factors that permit differentiation between two patient cohorts achieving US remission and clinical remission, and to determine the factors contributing to the discrepancy.Method: We reviewed 248 Japanese patients diagnosed with RA who underwent treatment with biological disease-modifying anti-rheumatic drugs at 13 centres. We performed US assessments of the synovia of 22 joints. We assessed the percentages of patients with clinical remission and US remission, defined as total power Doppler scores of 0 at 12 months.Results: The 87 patients who achieved US remission were divided into a group that achieved both clinical and US remission (n = 53) and a group that achieved US remission only (n = 34). Baseline factors that were significantly and independently associated with clinical remission at 12 months among patients who also achieved US remission included short disease duration, the presence of concomitant methotrexate use, and low patient global assessment score (p < 0.05, p < 0.05, and p < 0.005, respectively).Conclusions: RA patients with baseline high patient global assessment scores and long disease duration at baseline were unlikely to achieve clinical remission even after achieving US remission. Objective joint assessments using US provide additional information of potential importance for the management of RA. | |
| 33882329 | Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitiv | 2021 Aug 1 | This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug. | |
| 34394126 | Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State i | 2021 | This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0-25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS(+)) EVs; platelet (CD42a(+)), leucocyte (CD45(+)), monocyte (CD14(+)), and endothelial (CD144(+))-derived EVs; and EVs-expressing tissue factor (CD142(+)), P-selectin (CD62P(+)), and E-selectin (CD62E(+)) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS(+), CD42a(+), CD142(+), CD45(+), CD14(+), and CD62P(+) EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS(+), CD42a(+), CD14(+), and CD62P(+) EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS(+) and CD42a(+) EVs and OCP as well as between the levels of PS(+), CD42a(+), and CD62P(+)EVs and OHP. The levels of PS(+), CD42a(+), CD14(+), CD62P(+), and CD62E(+) EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease. | |
| 34562416 | Pancytopenia after Low-Dose Methotrexate Therapy in Two Hemodialysis Patients with Rheumat | 2022 Feb | Methotrexate (MTX) is an effective medication in the treatment of rheumatoid arthritis (RA), other rheumatic diseases and various solid tumors. However, its side effects, including gastrointestinal discomfort, oral ulcers, and especially bone marrow suppression, could be fatal and require special attention, particularly in patients with renal failure. We present two hemodialysis patients with RA who presented with a complication of severe pancytopenia after treatment with MTX. After receiving various supportive and blood purification treatments, both patients recovered. We reviewed twenty-four pancytopenia patients on dialysis associated with methotrexate. Among these patients, high morbidity and mortality were observed, indicating that MTX should be used cautiously in the absence of alternatives in such a population. Compared with the patients who recovered, the deceased patients showed a lower level of leukocytes. Which dialysis method might be the best choice is unclear. The mode of renal replacement therapy can be chosen according to the actual situation. | |
| 33153331 | Status of fracture risk assessment and osteoporosis treatment in Japanese patients with rh | 2021 Sep | OBJECTIVES: This study aimed to investigate the prevalence of patients with rheumatoid arthritis (RA) at a high risk of major osteoporosis (OP)-related fractures and the status of OP-related medical treatment for these patients. METHODS: We enrolled 120 patients aged ≥40 years (average, 69.1 years) with RA. The Fracture Risk Assessment Tool (FRAX(®)) was used to evaluate the fracture risk. Of the 120 patients, the femoral neck bone mineral density (BMD) was evaluated in 102 patients, and their FRAX(®) scores were calculated alongside the BMD values. Patients observed to be at a high risk of a major OP-related fracture (10-year probability >20% or hip fracture risk >3%), according to FRAX(®), were identified as those requiring OP treatment; medication ratio for OP (percentage of patients actually receiving medication among patients requiring OP treatment) was assessed. RESULTS: OP treatment was indicated in 75 (63%) patients; the medication ratio for OP was 49%. The use of biological disease-modifying anti-rheumatic drugs and corticosteroids showed a positive effect; however, the use of methotrexate showed a negative effect on the medication ratio. CONCLUSION: The number of potential patients requiring OP treatment is underestimated. All patients with RA should be assessed to determine their eligibility for OP treatment. | |
| 33897713 | MicroRNA Expression Differences in Blood-Derived CD19+ B Cells of Methotrexate Treated Rhe | 2021 | Rheumatoid arthritis (RA) is a complex disease with a wide range of underlying susceptibility factors. Recently, dysregulation of microRNAs (miRNAs) in RA have been reported in several immune cell types from blood. However, B cells have not been studied in detail yet. Given the autoimmune nature of RA with the presence of autoantibodies, CD19+ B cells are a key cell type in RA pathogenesis and alterations in CD19+ B cell subpopulations have been observed in patient blood. Therefore, we aimed to reveal the global miRNA repertoire and to analyze miRNA expression profile differences in homogenous RA patient phenotypes in blood-derived CD19+ B cells. Small RNA sequencing was performed on CD19+ B cells of newly diagnosed untreated RA patients (n=10), successfully methotrexate (MTX) treated RA patients in remission (MTX treated RA patients, n=18) and healthy controls (n=9). The majority of miRNAs was detected across all phenotypes. However, significant expression differences between MTX treated RA patients and controls were observed for 27 miRNAs, while no significant differences were seen between the newly diagnosed patients and controls. Several of the differentially expressed miRNAs were previously found to be dysregulated in RA including miR-223-3p, miR-486-3p and miR-23a-3p. MiRNA target enrichment analysis, using the differentially expressed miRNAs and miRNA-target interactions from miRTarBase as input, revealed enriched target genes known to play important roles in B cell activation, differentiation and B cell receptor signaling, such as STAT3, PRDM1 and PTEN. Interestingly, many of those genes showed a high degree of correlated expression in CD19+ B cells in contrast to other immune cell types. Our results suggest important regulatory functions of miRNAs in blood-derived CD19+ B cells of MTX treated RA patients and motivate for future studies investigating the interactive mechanisms between miRNA and gene targets, as well as the possible predictive power of miRNAs for RA treatment response. | |
| 33749319 | Influence of RFC1 c.80A>G Polymorphism on Methotrexate-Mediated Toxicity and Therapeutic E | 2021 Dec | BACKGROUND: Methotrexate (MTX) is an antirheumatic drug, transported by reduced folate carrier-1 (RFC1). The most common RFC1 gene variant, c.80 A>G (rs1051266) is ambiguously linked to adverse effects of MTX therapy in some rheumatoid arthritis (RA) patients. OBJECTIVE: The purpose of meta-analysis was to summarize all major published studies on c.80 A>G SNP to clarify this ambiguity in MTX therapy. METHODS: A total of 18 studies representing 3592 RA patients comprising 699 men and 2893 women were included. Both fixed and random effect models were applied to study the data. RESULTS: The RFC1 80A-allele showed null association with MTX-mediated toxicity in both fixed (odds ratio [OR] = 0.91; 95% CI = 0.80-1.03) and random effects (OR = 0.89; 95% CI: 0.71-1.11) models. Because heterogeneity was observed in this association (P = 0.0006), data were segregated based on use of folate therapy. In 7 studies (n = 1191) where folate was used along with MTX, RFC1 AA patients showed reduced risk for MTX-mediated toxicity (OR = 0.67; 95% CI: 0.50-0.89; P = 0.0006). The RFC1 80A-allele was found to increase the efficacy of MTX therapy by 1.53-fold (95% CI: 1.24-1.88), whereas the 80AA-genotype increased the efficacy by 1.85-fold (95% CI: 1.41-2.42). No publication bias was observed in these associations. CONCLUSION AND RELEVANCE: RFC1 c.80 A>G is an important pharmacogenetic determinant of MTX therapy in RA. The RFC1 80A-allele robustly increased therapeutic efficacy and safety when folate was used along with MTX. Findings are relevant to decision-making in the clinical use of MTX as a treatment for RA patients harboring the RFC1 gene variant. | |
| 33044386 | Adenosine Deaminase Gene Polymorphism and Baseline Serum Level of Adenosine Deaminase as a | 2021 Dec 1 | BACKGROUND: Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis (RA), but nearly 30% of RA patients do not respond to it. Methotrexate acts by enhancing the level of adenosine, which gets converted to inosine by the enzyme adenosine deaminase (ADA). We studied whether ADA gene polymorphism and serum levels of total ADA are associated with responsiveness to MTX. METHODS: Two hundred seven disease-modifying antirheumatic drug-naive active RA patients (DAS28-ESR [Disease Activity Score-28 for rheumatoid arthritis with erythrocyte sedimentation rate] ≥3.2) satisfying the European League Against Rheumatism (EULAR)/American College of Rheumatology 2010 criteria were enrolled. Genotyping was done in all patients, and in a subset (n = 59), blood was collected at baseline and at 2 months of MTX treatment for serum total ADA estimation by ELISA. Response at 4 months was assessed by EULAR criteria, and patients were classified as responders or nonresponders. The correlation of baseline clinical parameters, ADA gene polymorphism, and serum total ADA levels with EULAR response was sought. RESULTS: After 4 months of MTX monotherapy, 172 patients (83.1%) were classified as responders and 35 (16.9%) as nonresponders. Except DAS28-ESR (6.1 [5.43-6.84] in responders vs 5.6 [4.77-6.21] in nonresponders, p = 0.02), other baseline parameters (age, disease duration, ESR, and C-reactive protein level) were similar between responders and nonresponders. Single nucleotide polymorphisms in ADA gene, baseline serum ADA levels (10.52 ± 5.37 ng/mL in responders vs 12.28 ± 5.14 ng/mL in nonresponders), or change in ADA levels after 2 months of MTX therapy did not show any association with MTX response (p = 0.73, p = 0.34, p = 0.55, respectively). Adenosine deaminase genotype did not affect the blood ADA level. CONCLUSIONS: No association was seen between ADA single nucleotide polymorphism rs244076 as well as serum ADA level and response to MTX therapy. | |
| 34525992 | Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoi | 2021 Sep 15 | BACKGROUND: Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. METHODS: A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. RESULTS: Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. CONCLUSION: For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown. | |
| 34031262 | Short-term glucocorticoids reduce risk of chronic NSAID and analgesic use in early methotr | 2021 May | OBJECTIVE: To explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging. METHODS: Patients with eRA (≤1 year) and favourable risk profile (no erosions, negative rheumatoid factor and anticitrullinated protein antibodiesor low disease activity) in the 2-year CareRA trial were randomised to MTX 15 mg with a step-down GC scheme (COBRA Slim), or MTX without oral GCs, Tight-Step-Up (TSU). Used analgesics were recorded, including frequency, start/end date and indication. Chronic intake (≥90 consecutive days in trial) of NSAIDs, acetaminophen, opioids including tramadol and antidepressants for the indication of musculoskeletal (MSK) pain was considered. Treatments were compared using χ(2) and analysis of variance with Holm's correction for multiple testing. RESULTS: In total, 43 patients were randomised to COBRA Slim and 47 to TSU. At study inclusion, 33/43 (77%) of patients in the COBRA Slim and 32/47 (68%) in the TSU arm had been using analgesics (p=0.5). During the trial, 67 NSAID and analgesics were used for MSK pain in 26/43 (60%) COBRA Slim patients of which 9/43 (21%) daily chronically (DC), while 107 NSAID and analgesics were used in 43/47 (92%) TSU patients, of which 25/47 (53%) DC. The total number of patients on NSAID and analgesics at any time during the study (p<0.01) and chronically (p=0.01) was significantly different between treatment arms. Number of patients on DC NSAIDs was also significantly different (p<0.01) between COBRA Slim 6/43 (14%) and TSU 19/47 (40%). CONCLUSION: In eRA patients considered to have a favourable prognosis, initial oral GC bridging resulted in lower chronic NSAID and analgesic use. TRIAL REGISTRATION NUMBER: NCT01172639. | |
| 33970059 | Autopsy of a case of rheumatoid arthritis with severe bicytopoenia due to gelatinous trans | 2021 Jul | We present the case of an elderly female patient with rheumatoid arthritis (RA) treated with methotrexate. She was referred to our hospital with severe malaise. She was emaciated and had massive pleural effusion that induced atelectasis. Her blood tests revealed elevated CRP, leukopenia, and severe anaemia. She lost consciousness on the third day of hospital stay and passed away the following day. Her autopsy showed gelatinous transformation of the bone marrow that gave rise to bicytopoenia, whereas there were no other causes for severe anaemia. Bone marrow gelatinous transformation can cause impaired haematopoiesis in elderly RA patients. |