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ID PMID Title PublicationDate abstract
32141529 A review of network meta-analysis comparing biologics in the treatment of rheumatoid arthr 2020 Feb OBJECTIVE: Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents, it is still difficult to identify the most effective and safest available treatment. The choice and comparison between biological agents are a challenge, for only limited head-to-head clinical studies are available. The aim of this manuscript is to review the published network meta-analysis (NMA) to gain a better understanding of efficacy and safety of biological agents and small molecules in the management of RA patients. MATERIALS AND METHODS: We used MEDLINE and EMBASE to identify network meta-analyses from 2008 to June 2019 comparing efficacy and safety of licensed biological agents and tsDMARDS at the approved dosages using predefined text words related to the topic. The following scenarios have been investigated: patients not responding to csDMARD (cDMARDs - IR); csDMARD naïve patients; patients not responding to biologics (bDMARDs - IR); patients in biological monotherapy. RESULTS: On the basis of the data present in the literature, we are able to hypothesize some trends of response in terms of efficacy in different subsets of patients, for example patients in monotherapy, bDMARds unresponsive patients, and Methotrexate-naive patients. The differences of the results presented in many works are due to the different inclusion criteria used in the studies, the type of biologics agent used in each study (according to the available molecules in the different years of publication), as well as differences in the methodology of NMA and in the presentation of the data. CONCLUSIONS: We suggest that the next NMA follows the indications suggested by the Professional Society for Health Economics and Outcomes Research (ISPOR) so that the results are comparable and comprehensible.
31756165 Autoimmune polyglandular syndrome type 3 variant in rheumatoid arthritis. 2020 Mar 1 INTRODUCTION: Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant. CASE REPORT: A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy. CONCLUSION: In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.
31843461 Auxiliary in vitro and in vivo biological evaluation of hydrogen peroxide sensitive prodru 2020 Jan 15 Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe joints damage and other extra-articular alterations. Despite the efficacy of low-dose methotrexate (LD-MTX) in RA treatment, adverse effects are the predominant reasons for discontinuation of therapy. As a therapeutic targeting strategy, the presence of increased concentrations of reactive oxygen species (ROS) in the inflammatory environment can serve as the stimulus for prodrug activation in site-selective drug delivery systems. Our group has previously reported novel ROS sensitive prodrugs (1-3) of MTX and aminopterin (AMT) for site-selective delivery to inflammatory tissue associated with RA, with the aim of reducing side effects in RA therapy. Herein, we investigate the effect and toxicity of the same prodrugs in a rat CIA (collagen-induced arthritis) model of RA. We find that prodrug 1, an arylboronic acid ROS-sensitive MTX-prodrug, displays similar in vivo efficacy as MTX at an equimolar dose, while avoiding adverse effects known to restrict MTX treatment. To further characterize prodrug 1 and its ROS mediated activation, we synthesized compound 4, a negative control lacking the boronic acid moiety. We then investigated the effect of molecules on cell proliferation and cytotoxicity in the presence of the ROS scavenger pyruvate, as well as their stability in buffer and cell media, demonstrating a direct correlation between ROS concentration and the prodrug activity. Moreover, the in vitro ADME properties were investigated, including permeability, rat plasma and microsomal stability.
32876784 Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. 2021 Apr OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs). METHODS: Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported. RESULTS: After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity. CONCLUSION: Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.
33338001 Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life 2021 Jul OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.
32969462 A rapid response near-infrared ratiometric fluorescent probe for the real-time tracking of 2020 Oct 21 Peroxynitrite (ONOO-) is a potent bio-oxidant involved in many physiological and pathological processes; however, most of the pathological effects associated with ONOO-in vivo are still ambiguous. Herein, we designed and synthesized two near-infrared ratiometric fluorescent probes, Ratio-A and Ratio-B, for the detection and biological evaluation of ONOO-. The recognition unit diene in the probes could be specifically cleaved by ONOO- with a 94-fold enhancement in the ratiometric fluorescence signal. By imaging ONOO- in immune stimulated cells and acute inflammation mice model using Ratio-A, we investigated the fluctuations of ONOO- levels in a rheumatoid arthritis (RA) model of mice. Ratio-A could be applied for the effective imaging of RA and could rapidly evaluate the response of the RA treatment with methotrexate (MTX). Thus, Ratio-A can be considered as a promising tool for pathological diagnosis and the therapeutic assessment of a wide range of diseases including RA.
32539800 Influence of age on the occurrence of adverse events in rheumatic patients at the onset of 2020 Jun 15 OBJECTIVES: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. RESULTS: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. CONCLUSION: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.
32757110 The advances of methotrexate resistance in rheumatoid arthritis. 2020 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is characterized by a chronic fluctuating course and immune dysfunction, resulting in affecting the health and life quality of RA patients. Methotrexate (MTX), as the standard gold treatment of RA, has received more and more clinical applications and basic pharmacological research. In several observational studies, MTXR, and treatment responses in RA patients show that the ratio of MTXR and non- response is about 30%-50%, namely MTX resistance (MTXR). Extensive efforts have been made into the investigation of the mechanism and effective biomarkers in MTXR of RA. In this paper, we discuss the recent findings regarding the critical signaling pathways of MTXR in RA. Provide research targets and directions for a drug therapy that develop preventive strategies and effective treatments of MTXR.
33338006 Methotrexate in Italian patients wiTh Rheumatoid Arthritis (MITRA study): an observational 2021 Sep OBJECTIVES: To assess the delay between the disease onset and the beginning of methotrexate (MTX) treatment in RA patients and to evaluate the Italian rheumatologists' adherence to the EULAR 2013 recommendations. METHODS: MITRA is an Italian multicentre observational study carried out on DMARD-naïve RA patients recruited in an 18-month period starting from 2015. The data related to the patients' characteristics at baseline will be presented. RESULTS: 332 patients from 13 Italian centres were recruited: the median delay between the onset of symptoms and the beginning of MTX was 197 days (102-431); in 20% of patients a treatment with DMARDs was started within the first 90 days from the onset of symptoms. The clinical target selected was DAS28 remission in 64.2% of cases and low disease activity in 35.8%. Among patients in DAS28 high disease activity, 92.6% received a control visit which was rescheduled within the first 3 months, similarly to those in DAS28 moderate disease activity (91.6%). A DMARD monotherapy was prescribed in 319 patients, while a combined therapy of DMARDs was preferred in 13 cases; 282 patients were treated with MTX. Glucocorticoids were prescribed in 229 patients: the median dosage was of 5 mg (IQR 5-7.5) of prednisone equivalent/day. CONCLUSIONS: Diagnostic delay in RA patients continues to be longer than expected. The choice of low disease activity as a target is still very frequent and tight control does not seem to be based on disease activity. This paper offers a realistic and detailed picture of the clinical practice among Italian rheumatologists.
33201634 [Risk factors for disseminated herpes zoster]. 2020 Sep 16 BACKGROUND: When skin abnormalities in patients extend over several dermatomes, disseminated herpes zoster should be suspected. This complication is most often seen in immunocompromised patients. CASE DESCRIPTION: An 87-year-old patient came to the dermatology outpatient clinic with several vesicles scattered over her body. She was being treated with methotrexate for rheumatoid arthritis. Upon physical examination, we found groups of vesicles in the area of the maxillary nerve as well as several solitary vesicles scattered over her body. We made the diagnosis of 'disseminated herpes zoster'. PCR test of fluid from one of the vesicles found Varicella zoster virus. We treated the patient with intravenous acyclovir for 48 hours after which we treated her with oral acyclovir for another 8 days. We temporarily halted methotrexate. Outpatient follow-up found that the patient's skin abnormalities had diminished significantly. CONCLUSION: The risk of disseminated herpes zoster depends on several factors. Use of immunosuppressants is often not the only contributing factor. Risk of disseminated herpes zoster in a patient who is being treated with methotrexate depends on age, comorbidities and co-medication of the patient.
31549885 Association of HLA-G 3'UTR Polymorphisms with Soluble HLA-G Levels and Disease Activity in 2020 Feb Background: Human leukocyte antigen (HLA)-G antigens are inducible non-classical major histocompatibility complex class Ib molecules which play an important role in the regulation of inflammatory processes and immunomodulation in autoimmune diseases. There are controversial reports on the impact of HLA-G gene polymorphisms on rheumatoid arthritis (RA). This study aimed at examining the impact of 14 base pair (bp) ins/del (rs66554220) and +3142G>C (rs1063320) polymorphisms and correlating these with soluble HLA-G (sHLA-G) levels to understand the susceptibility to RA in our sample cohort.Methods: Genomic DNA from 140 RA patients and 125 healthy controls was isolated using the salting out method. The genotyping of two polymorphisms of HLA-G (+3142G>C and 14 bp ins/del) was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR method, respectively. Levels of sHLA-G were estimated by ELISA and disease activity was calculated by disease activity score (DAS28-ESR).Results: The HLA-G +3142G>C polymorphism was found to be associated with a decreased risk of RA as attributed to recessive inheritance tested model results (OR = 0.4, 95%C.I. = 0.2-0.9, p = .0313*, GG + GC versus CC). Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. The sHLA-G levels were significantly lower in +3142GG and +3142GC RA patients as compared to healthy controls.Conclusion: HLA-G +3142G>C gene polymorphism might decrease the risk of occurrence of RA in our sample cohort as +3142CC genotype is associated with increased sHLA-G levels.Abbreviations: HLA-G: human leukocyte antigen-G; RA: rheumatoid arthritis; MHC: major histocompatibility complex; UTR: untranslated region; URR: upstream regulatory region; SLE: systemic lupus erythematous; PCR-RFLP: polymerase chain reaction restriction fragment length polymorphism; sHLA-G: soluble HLA-G; bp: base pair; ACR/EULAR: American College of Rheumatology/European League against Rheumatism; RF: rheumatoid factor; Anti-CCP: anti-cyclic citrullinated peptide; DAS28-ESR: Disease Activity Score 28- Erythrocyte Sedimentation Rate; TJC: tender joint count; SJC: swollen joint count; ESR: erythrocyte sedimentation rate; PGA: patient global assessment; HTN: hypertension; DM: diabetes mellitus; TB: tuberculosis; IEC: Institute Ethics Committee; ELISA: enzyme linked immunosorbent assay; ROC: receiver operating characteristics; AUC: area under curve; SNP: single nucleotide polymorphism; MTX: methotrexate; DMARDs: disease modifying anti-rheumatic drugs; Treg: regulatory T cells; IL: interleukinUnits: soluble HLA-G: Units/mL {U/mL}.
32361822 Understanding Refractory Rheumatoid Arthritis: Implications for a Therapeutic Approach. 2020 Jun Refractory rheumatoid arthritis (RA) has emerged as an area of unmet need in a landscape of generally well-controlled disease. Whilst most patients are adequately treated on methotrexate and other first-line disease-modifying anti-rheumatic drugs (DMARDs), a proportion requires biologic (b) and targeted synthetic (ts) DMARDs, with a further subsection failing multiple agents. Recent observational studies have adopted working definitions of refractory RA based on number of failed DMARDs, with prevalence estimates of 6-21% depending on threshold and study population. Risk factors include treatment delay, baseline disease activity and function, female gender, smoking, obesity and lower socioeconomic status. Practical and conceptual challenges in defining refractory RA arise from limitations of disease activity scores used to assess response, with attendant misclassification risk of co-existent non-inflammatory pathology, and failure to capture additional outcomes, such as fatigue, that have variable treatment response. Time is an important factor in defining refractory disease; registry studies show that growing treatment options have resulted in rapid b/tsDMARD cycling and earlier refractory status, and refractory RA is itself a dynamic concept, evolving with each new therapeutic class. Whilst the biology underpinning refractory RA remains largely unknown, a general overview of biomarker studies and clinical trials old and new offers insights into prediction of response and treatment failure. Whilst the future holds promise, current data are insufficient to personalise or meaningfully sequence b/tsDMARDs. Therefore, avoidance of a refractory course is best achieved by following proven management paradigms (e.g. early diagnosis and treat-to-target), addressing modifiable risk factors, and considering enrolment in novel trials.
32996384 The Effect of Dose Escalation on the Cost-Effectiveness of Etanercept and Adalimumab with 2020 Oct BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) occasionally increase their doses of tumor necrosis factor (TNF) inhibitors, especially the monoclonal antibody origin drugs such as adalimumab and infliximab, after inadequate response to the initial dose. Previous studies have evaluated the cost-effectiveness of various sequences of treatment for RA in the United States but have not considered the effect of dose escalation. OBJECTIVE: To assess the cost-effectiveness of etanercept and adalimumab by incorporating the effect of dose escalation in moderate to severe RA patients. METHODS: We adapted the open-source Innovation and Value Initiative - Rheumatoid Arthritis model, version 1.0 to separately simulate the magnitude and time to dose escalation among RA patients taking adalimumab plus methotrexate or etanercept plus methotrexate from a societal perspective and lifetime horizon. An important assumption in the model was that dose escalation would increase treatment costs through its effect on the number of doses but would have no effect on effectiveness. We estimated the dose escalation parameters using the IBM MarketScan Commercial and Medicare Supplemental Databases. We fit competing parametric survival models to model time to dose escalation and used model diagnostics to compare the fit of the competing models. We measured the magnitude of dose escalation as the percentage increase in the number of doses conditional on dose escalation. Finally, we used the parameterized model to simulate treatment sequences beginning with a TNF inhibitor (adalimumab, etanercept) followed by nonbiologic treatment. RESULTS: In baseline models without dose escalation, the incremental cost per quality-adjusted life-year of the etanercept treatment sequence relative to the adalimumab treatment sequence was $85,593. Incorporating dose escalation increased treatment costs for each sequence, but costs increased more with adalimumab, lowering the incremental cost-effectiveness ratio to $9,001. At willingness-to-pay levels of $100,000, the etanercept sequence was more cost-effective compared with the adalimumab sequence, with probability 0.55 and 0.85 in models with and without dose escalation, respectively. CONCLUSIONS: Dose escalation has important effects on cost-effectiveness and should be considered when comparing biologic medications for the treatment of RA. DISCLOSURES: Funding for this study was contributed by Amgen. When this work was conducted, Incerti and Jansen were employees of Precision Health Economics, which received financial support from Amgen. Maksabedian Hernandez, Collier, Gharaibeh, and Stolshek were employees and stockholders of Amgen, and Tkacz and Moore-Schiltz were employees of IBM Watson Health, which received financial support from Amgen. Some of the results of this work were previously presented as a poster at the 2019 AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28, 2019, in San Diego, CA.
32896992 Weekly split-dose regimen for oral methotrexate reduced polyglutamation in red blood cells 2020 Oct AIMS: We compared the incidence of adverse events between single and divided-dose regimens of methotrexate (MTX) by using a multicenter randomized controlled trial. METHODS: Eighty-nine patients with insufficient control on MTX 8 mg/wk were randomly assigned into single-dose (39 patients) or triple dose (39 patients) groups. The MTX dose for all patients was gradually increased to 16 mg/wk. The primary endpoint was the occurrence of liver dysfunction during the observation period (20 weeks). RESULTS: There were no differences in baseline data and MTX dose at Week 20 between groups. There was no significant difference in the incidence of liver dysfunction between groups (single dose, 3 [7.7%] patients vs. triple dose, 5 [13.2%] patients; P = .455). The incidence of adverse event increased in triple dose (single dose, 12 [30.8%] patients vs. triple dose, 20 [51.3%]), but the difference was not significant (P = .066). There was no significant difference in disease activity between groups, although MTX-triglutamate (PG3), MTX-PG4, and MTX-PG5 were significantly higher in the single dose group. CONCLUSIONS: Weekly split dosing reduced the polyglutamation of MTX. There was no significant difference in efficacy and safety between the 2 groups.
32300908 Association of cytokine patterns and clinical/laboratory parameters, medication and period 2020 Jul To evaluate serum levels of the following cytokines in rheumatoid arthritis subjects with periodontal disease: Interleukin-6, -10, -17, and -23. Patients with rheumatoid arthritis frequently suffer from periodontal disease. Both diseases partly result from a dysregulated immune response. The current study aimed to quantify Interleukin-6, -10, -17, and -23 levels in rheumatoid arthritis. It should be investigated if the periodontal disease would have additional modifying effects. A total of 157 patients were included. Serum levels of IL-6, -10, -17, and -23 were measured by ELISA. Serum IL-10 increased with longer duration of morning stiffness and with higher rheumatoid factor and anti-cyclic citrullinated peptide titres. IL-10 was also elevated with longer duration of prednisolone (< 5 mg daily) and leflunomide therapy. Subjects with lower erythrocyte sedimentation rate/longer leflunomide therapy displayed more missing teeth/more clinical attachment loss. IL-17 was higher in subjects with fewer missing teeth if the following criteria were fulfilled: shorter prednisolone (< 5 mg) and methotrexate therapy, more swollen joints, longer morning stiffness. IL-23 finally was increased in subjects with higher rheumatoid factor and in those with higher periodontal probing depth/clinical attachment loss in the following situations: lower rheumatoid factor and shorter leflunomide therapy. Subjects suffering from dental/periodontal burden show an aberrant systemic cytokine availability of serum IL-6, IL-10, IL-17 and IL-23 related to disease activity and medication. This examination underlines the complexity of potential interactions between disease activity and medication related to periodontal burden.
33016574 Prevalence of patients with rheumatoid arthritis and age-stratified trends in clinical cha 2020 Dec AIM: To estimate the prevalence and age-stratified treatment trends and clinical characteristics of rheumatoid arthritis (RA) in Japan. METHOD: Using 7 RA definitions, the prevalence of RA in those aged ≥16 years was estimated using the National Database of Health Insurance Claims and Specific Health Checkups of Japan in the fiscal year 2017. We analyzed age-stratified trends in characteristics and treatments. RESULTS: Of 1 116 122 patients aged ≥16 years with at least 1 RA-related International Classification of Diseases-10 code, 825.7 thousand patients (women, 76.3%) were assessed as having RA with an estimated prevalence of 0.65%. The highest age-stratified prevalence was 1.63% in patients aged 70-79 years. Overall, 60.8% and 7.0% of patients with RA were aged ≥65 years and ≥85 years, respectively. Methotrexate use was most frequent in patients aged 50-59 years (73.0%) and least frequent in patients aged ≥85 years (38.2%). Biologic disease-modifying antirheumatic drugs use was 50.9% in patients aged 16-19 years and decreased to 13.7% in those aged ≥85 years. Preference for the use of tumor necrosis factor inhibitors versus abatacept decreased from 24.0:1 to 1.7:1 in patients aged 16-19 years and ≥85 years, respectively. The prevalence of cardiovascular disease was 3.5% in patients aged 60-69 years and 12.1% in those aged ≥85 years. Overall RA-related orthopedic surgeries were most prevalent in patients aged 70-79 years. CONCLUSION: The estimated prevalence of patients with RA in Japan was 0.65%. Age-stratified treatment trends and clinical characteristics have been described in a super-aged society for the first time.
33198544 Combination therapy of ginsenoside compound K and methotrexate was efficient in eliminatio 2020 Dec CONTEXT: Ginsenoside compound K (CK) has anti-inflammatory, immunoregulatory, and myelosuppressive protective effects. Methotrexate (MTX) is widely used in combination therapy for rheumatoid arthritis (RA). OBJECTIVE: To evaluate the effects of combination therapy of CK and MTX on anaemia and anti-arthritis in adjuvant-induced arthritis (AA) rats. MATERIALS AND METHODS: AA was induced in rats by Complete Freund's adjuvant, and divided into five groups (n = 10): normal, AA, CK 80 mg/kg, combination therapy (80 mg/kg CK combined with 0.5 mg/kg MTX), and MTX 0.5 mg/kg. From day 12, CK (once a day for 15 days) or MTX (once every 3 days, five times) were intragastrically administered. RESULTS: Combination therapy showed increased haemoglobin to 148.5 ± 10.1 g/L compared with AA (129.8 ± 11.7 g/L) and MTX (128.8 ± 18.4 g/L), and decreased reticulocytes in peripheral blood to 4.9 ± 1.1% compared with MTX (9.3 ± 3.3%). In combination therapy group, paw swelling decreased to 5.6 ± 4.3 mL compared with CK (9.4 ± 3.9 mL) and MTX (13.5 ± 7.4 mL), and swollen joint count decreased to 1.4 ± 0.8 compared with CK (2.1 ± 1.0) and MTX (2.4 ± 1.2) at day 24. Combination therapy showed decreased IL-6 to 25.1 ± 17.2 pg/mL compared with MTX (44.9 ± 4.8 pg/mL), and decreased IL-17 to 5.8 ± 3.9 pg/mL compared with MTX (10.7 ± 4.2 pg/mL). CONCLUSION: The anti-anaemia effect of CK deserves further study, and CK can be a candidate effective drug for combined treatment in RA with anaemia.
32024416 MTHFR, TYMS and SLCO1B1 polymorphisms and adverse liver effects of methotrexate in rheumat 2020 Apr Aims: To investigate whether variants of MTHFR, TYMS and SLCO1B1 are associated with ALT elevation in rheumatoid arthritis patients starting methotrexate (MTX). Patients & methods: Clinical and laboratory data were collected from the start of MTX treatment. Genotyping of MTHFR, TYMS and SLCO1B1 was performed. Univariate and multiple logistic regression were used for statistical analysis. Results: 34 out of 369 patients experienced ALT >1.5 × ULN less than 6 months from start. MTHFR A1298C (rs1801131) was nominally associated with an ALT >1.5 × ULN within 6 months after the start of MTX (OR = 1.7 [95% CI: 1.04-2.9]; p = 0.03), but did not pass correction for multiple testing. A multiple model containing MTHFR 1298C and clinical factors predicted the outcome (C-statistic 0.735). TYMS and SLCO1B1 were not associated with the outcome. Conclusions: A model containing MTHFR 1298C and clinical factors might predict risk of early ALT elevation.
32370467 [A survey on therapy strategies for rheumatoid arthritis in Chinese rheumatologists]. 2020 May 1 To investigate how Chinese rheumatologists treated patients with rheumatoid arthritis (RA). We performed a survey on the choices of first-line and second-line anti-RA therapies, prescription of methotrexate and glucocorticoids, assessment of disease activity and frequencies of follow-up at the Asia Pacific League of Associations for Rheumatology meeting 2016 in Shanghai. The majority (85.1%) of rheumatologists preferred methotrexate as first-line treatment. As alternative agents, 71.0% rheumatologists chose leflunomide or sulfasalazine. If methotrexate was not tolerable, only 8.6% rheumatologists would switch to parenteral administration. After failure of responding to methotrexate, 62.0% rheumatologists recommended to change or combine other conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). Etanercept was the most popular biological option in 65.2% rheumatologists. Almost all (97.3%) rheumatologists prescribed methotrexate at an initial dose of 7.5 to 15 mg/week and 73.8% rheumatologists at a maximum of 10 to 15 mg/week. There were 49.3% rheumatologists prescribing oral glucocorticoids at first-line therapy. Surprisingly, 42.6% rheumatologists never or rarely assessed disease activity in daily work. For patients having achieved remission, 74.2% rheumatologists would follow up them every 1 to 3 months. This study suggests that most Chinese rheumatologists treat RA patients consistent with international guidelines, while the maximum dose of methotrexate, glucocorticoid as first-line treatment, assessment of disease activity and follow-up frequency are locally modified.
31571513 Pathological assessment of the lymph node biopsies for lymphadenopathy in rheumatoid arthr 2020 Sep Objectives: To assess the incidence of reactive lymph node hyperplasia (RLH) and the diagnostic characteristics that can help differentiate it from lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA).Methods: Data on patient characteristic from 32 consecutive RA patients with lymphadenopathy at a single medical center over a 6-year period were collected and analyzed to determine whether any of these characteristics can differentiated RLH from LPD.Results: LPD including methotrexate (MTX) - associated LPD (MTX-LPD) and RLH were diagnosed in 19 and 10 patients, respectively. Conclusive diagnosis was not reached in the remaining three cases and they were regarded as grey-zone cases. Age, levels of lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R), as well as maximum standardized uptake value (SUV(max)), were significantly higher in LPD than in RLH patients. The diagnosis cut-off values for these parameters were 66 year, 169 U/L, 899 U/mL and 8.18, respectively, based on the receiver operating characteristics curve analysis for both RLH and LPD.Conclusions: About one-third of patients with RA who presented with lymphadenopathy had reactive lymph node enlargement. Older age and higher levels of LDH, sIL-2R, and SUV(max) are more associated with LPD than should be considered when deciding to perform a biopsy.