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ID PMID Title PublicationDate abstract
31497770 Accelerated Nodulosis in a Patient With Rheumatoid Arthritis. 2019 Jun In patients with rheumatoid arthritis (RA), subcutaneous nodules are the most frequently seen extra-articular findings that are seen in areas of extensor pressure. In this article, we present the case of a RA patient with accelerated nodulosis that started with the use of methotrexate and exacerbated with etanercept and leflunomide treatment.
30112132 Atraumatic Insufficiency Fractures of the Tarsal Bones - An Unusual Cause of Recurrent Hee 2018 Jul The incidence of insufficiency fractures is approximately 1% in rheumatoid arthritis patients. The predisposing factors are chronic inflammation, skeletal deformities, biomechanical stresses and osteoporosis. The medications used in the treatment of rheumatoid arthritis such as Glucocorticosteroids and Methotrexate also contribute to the development of osteoporosis and insufficiency fractures. A 68-year old lady who was suffering from rheumatoid arthritis and on long term Methotrexate was seen in the outpatient clinic with recurrent episodes of heel pain. Examination revealed diffuse tenderness around the heel with full range of ankle movements but painful limitation of subtalar joint movements. Radiographic examination of the ankle showed a highly suspicious fracture of the calcaneus and confirmed on MRI as an insufficiency fracture. She was treated successfully with oral bisphosphonates and moon boot brace. She presented after two years with recurrent episodes of heel pain. The plain radiograph and MRI scan confirmed an insufficiency fracture of the talus. She was treated non-operatively with intravenous Zolendronic acid and bracing. In chronic rheumatoid arthritis patients especially on Methotrexate and Glucocorticoids a high index of suspicion of insufficiency fractures should be considered if they present with bone pain. MRI scan is the investigation of choice and is conclusive.
29686436 Methotrexate treatment for rheumatoid arthritis in Poland: Retrospective analysis of patie 2018 OBJECTIVES: The aim of this study was to evaluate methotrexate (MTX) treatment administered by Polish rheumatologists in everyday practice. MATERIAL AND METHODS: The study was based on a retrospective analysis of a cohort of 1957 patients with rheumatoid arthritis (RA). It was conducted among 100 rheumatologists, each of whom received 20 questionnaires and completed them based on the data from their rheumatoid arthritis patients. RESULTS: Methotrexate was taken by 91% of patients, and 80% of them continued the treatment either as a monotherapy (65%) or concomitantly with other disease-modifying anti-rheumatic drugs. In 60% of the cases, therapy was initiated within six months of diagnosis. Dose modifications were observed in 76% of cases and were contingent on different factors, e.g. lack of efficacy, presence of adverse events. The most prevalent adverse events were nausea and vomiting, weakness, and elevated liver enzyme activity. The most common initial dose of MTX was 10 or 15 mg/week. An increase in dose to the maximum of 25 mg/week was observed in 36% of cases, with continuation for 27% of patients. Treatment interruption was noted in 21% of patients, predominantly due to MTX intolerance; however, in 13% of cases, it was due to patient choice. CONCLUSIONS: Methotrexate is the most common agent used to treat rheumatoid arthritis. Dose modifications are often applied to maximise efficacy and reduce adverse reactions, which could lead to withdrawal. Methotrexate is an effective drug for treatment of RA when used according to current recommendations. To optimise MTX therapy, regular medical visits are required.
32185319 Canakinumab for refractory RA: a case report. 2018 Sep Rheumatoid arthritis is a common autoimmune disease leading often to joint destruction and reduced quality of life. We report a case of a young woman with rheumatoid arthritis with fever and rapid, destructive joint involvement verified with magnetic resonance imaging. She had failed therapy with methotrexate and leflunomide, anti-TNF, IL-6 inhibitor, B cell depletion and IL-1RA. Her laboratory results remained insignificant despite the aggressiveness of her disease. In this case, the patient only partly responded to anakinra but developed side effects, and therefore was switched to Canakinumab that led to sustained remission. There are no clear biomarkers or other clues in order to separate early in the beginning of the disease course if a polyarticular inflammatory spectrum can be IL-1β driven. The young age of the patient at onset of disease, its aggressive course, inflammatory fever without significant laboratory inflammatory markers but with polyarthritis affecting small joints, may raise the suspicion of an IL-1β-driven disease and alert the treating rheumatologist to the use of IL-1β inhibitors early in the disease course.
30155252 Lymphoproliferative disorder in an elderly rheumatoid arthritis patient after longterm ora 2018 Sep Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is frequently reported in the literature; however, its pathophysiology has not been fully elucidated to date. We herein describe a case of MTX-LPD that occurred after long-term treatment with oral MTX in a 67-year-old Japanese woman with rheumatoid arthritis (RA) who presented with generalized lymphadenopathy of the neck. The patient had been diagnosed with RA 24 years earlier, and had been on oral MTX for 20 years. The patient noticed a mass on her neck, which prompted a visit to our hospital. The mass was confirmed as diffuse large B-cell lymphoma by biopsy. MTX treatment was discontinued, which resulted in a reduction in the size of the mass and improvement of the patient's symptoms. Therefore, clinicians must be aware of MTX-LPD as a differential diagnosis for patients with rheumatological conditions on long-term MTX therapy presenting with signs and symptoms suggestive of lymphoma.
29922080 Factors correlated with the improvement of endothelial dysfunction during Abatacept therap 2018 BACKGROUND: Rheumatoid arthritis patients are exposed to a high risk of cardiovascular morbidity and mortality even in the early phases of the disease. METHODS: We evaluated carotid common carotid intimal media thickness (ccIMT) intimal thickness and brachial flow-mediated dilation (FMD) of 45 rheumatoid arthritis patients without known cardiovascular risk factors or heart disease on a stable dose of prednisone 5.2±1.2 mg/day and Methotrexate 11.5±2.1 mg at baseline (T0) and after 12 months (T1) of treatment with Abatacept 125 mg/week. The comparison between T0 and T1 (t- and Mann-Whitney test), correlation (Spearman r), and predictivity (linear regression) of FMD, ccIMT vs clinical and laboratory parameters (disease activity 28 score, tumor necrosis factor alpha [TNFα], interleukin-6, erythrocyte sedimentation rate, C-reactive protein (CRP), CD3+, CD3+/CD4+, CD3+/CD8+, CD19+(B), CD20+(B), NK CD3-CD56+CD16+, CD14+ HLA DR+, CD4+CD28+, CD4+CD28, rheumatoid factor IgM, IgA, RF IgG, anti-citrullinated peptide antibodies) were also evaluated. RESULTS: During Abatacept treatment, ccIMT and FMD remained stable and disease activity 28 score, CRP, erythrocyte sedimentation rate, and interleukin-6 decreased significantly (p=0.0001, 0.002, 0.0002, 0.0001 respectively). At T0, only ccIMT resulted as correlated with baseline TNFα values (p=0.0245) in an inverse proportion. At T1, ccIMT correlated with CD3/CD8+ lymphocytes number (p=0.0351) and FMD with CRP (p=0.0075). In regression analysis, baseline ccIMT and FMD had a low predictivity for TNFα (p=0.011) and CRP (p=0.049) at T1, respectively. CONCLUSION: This study shows that the endothelial function remained stable during Abatacept treatment.
30325625 2018 Mar The objective of this review is to assess the benefits and harms of drugs used in adult patients with moderate to severe rheumatoid arthritis (RA) in whom treatment with methotrexate (MTX) has failed or who are intolerant to MTX.
30627294 Management of Inflammatory Cardiac Masses. 2018 Dec Systemic rheumatologic and inflammatory disorders can affect almost any organ system, including the heart. The cardiac valves, conduction system, myocardium, endocardium, pericardium, and coronary arteries may be affected. Intracardiac masses may develop as part of the disease process or a consequence of their therapy, such as methotrexate-associated nodulosis. Optimal therapy in these cases is not known, since many patients are asymptomatic and the potential benefit of surgical excision must be weighed against its associated morbidity and mortality. Importantly, these inflammatory masses must be differentiated from thrombus, infection, and primary and metastatic tumors. We present three cases of inflammatory cardiac masses associated with rheumatoid arthritis and Wegener's granulomatosis, which were successfully treated conservatively, and propose a management algorithm. The benefits of such an approach must be individualized and weighed against the risks of systemic embolization, stroke and obstruction.
30567235 Treatment of advanced stage methotrexate-associated lymphoproliferative disorders (MTX-LPD 2018 Dec 13 We present two cases of patient's with long-standing autoimmune diseases being treated with immunosuppressants that developed aggressive lymphoproliferative disorders. Immunosuppressants have a well-known association with disorders. Sustained regression of these lymphoproliferative disorders occurred with simple discontinuation of these immunosuppressive agents.
30101019 Lymphoproliferative disorder with pathological fracture of the femur in a patient with rhe 2018 Aug Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis (RA). MTX-treated RA has been associated with the development of lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration may contribute to development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues, at an almost equal frequency. However, it is rare for MTX-LPD to manifest as multiple bone tumors with a pathological fracture. The present study reported the case of a 46-year-old Japanese woman with RA who had complications of EBV-positive MTX-LPD during an approximate 5-year course of MTX therapy. The present study indicated a rare case in which the LPD had spread to multiple bones in a patient with a pathologic fracture. Notably, the LPD was subclassified as diffuse large B-cell lymphoma (DLBCL).
29900970 The Association of Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibodies in Patie 2018 Mar OBJECTIVES: This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. PATIENTS AND METHODS: We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. RESULTS: Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p<0.05). Levels of anti-threonyl-tRNA-synthetase (anti-PL-7) and anti-alanyl-tRNA-synthetase (anti-PL-12), two anti-ARS antibodies, were higher in RA patients with concurrent ILD (both p<0.05). Myositis and ILD worsening were not observed in three anti-ARS antibody- positive patients despite biological disease modifying antirheumatic drug administration. There was no difference in anti-cyclic citrullinated peptide and rheumatoid factor specificities between patients with or without ARS antibodies. CONCLUSION: Anti-ARS antibodies were detected in RA patients, with higher prevalence in patients with concurrent ILD. RA patients, specifically those with ILD complications, should be tested for anti-ARS antibodies.
30679969 Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases. 2019 Feb The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.
30048923 Methotrexate prodrugs sensitive to reactive oxygen species for the improved treatment of r 2018 Aug 5 Methotrexate (MTX) is the standard of care in the treatment of rheumatoid arthritis (RA), a common autoimmune disease that is characterized by chronic inflammation in the synovial membrane of joints. Unfortunately, MTX suffers from high discontinuation rates due to a large variability in efficacy and, in particular, adverse effects. As inflammation is associated with elevated levels of reactive oxygen species (ROS) like H(2)O(2), we propose to improve treatment through site-selective delivery of MTX to inflammatory tissue by use of a H(2)O(2) sensitive MTX prodrug. To establish proof proof-of-concept, two novel H(2)O(2) sensitive, thiazolidinone-based MTX prodrugs were synthesized and evaluated for this purpose. MTX-γ-thiazolidinone (MTX-γ-TZ) exhibited the most promising properties - good to high chemical and metabolic stability, excellent aqueous solubility, while being activated when subjected to patho-physiological concentrations of H(2)O(2). In vivo, MTX-γ-TZ exhibited comparable efficacy to MTX in a murine collagen type II-induced arthritis (CIA) model while treated mice showed indications of reduced toxicity as their body weight decreased less towards the end of the study, compared to the MTX-treated group.
32743356 Spontaneous regression of a renal mass and multiple lung nodules after methotrexate cessat 2018 Nov INTRODUCTION: Methotrexate has been reported to increase the risk of lymphoproliferative disorders. We report a rare case who was clinically diagnosed with methotrexate-associated lymphoproliferative disorders of the kidney. CASE PRESENTATION: A 77-year-old patient with rheumatoid arthritis had taken low-dose methotrexate for 13 years. The patient developed left renal mass 3 cm in size and multiple pulmonary nodules. Initially, renal malignant tumor with lung metastases was considered and the renal biopsy was planned. However, under possible diagnosis of methotrexate-related lymphoproliferative disorder, we withdrew methotrexate treatment at first and then observed spontaneous regression of the tumorous lesions of the kidney and lungs. CONCLUSION: Although methotrexate-related lymphoproliferative disorder in kidneys is very rare, our case advocates the importance of a relevant differential diagnosis of methotrexate-related lymphoproliferative disorder under the setting of long-term treatment of methotrexate for rheumatoid arthritis.
29470832 Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheuma 2018 Jun INTRODUCTION: The aim of this study was to investigate real-world treatment patterns for use of golimumab and concomitant medications in Japanese patients with rheumatoid arthritis. METHODS: This study was a post hoc retrospective analysis from post-marketing surveillance data on 2350 Japanese patients with moderate/severe rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided based on initiation treatment or dose adjustment patterns with golimumab, methotrexate, or oral glucocorticoids. RESULTS: Logistic regression analysis revealed that the baseline factors associated with administration of golimumab (100 mg) were higher body weight, failure of prior biological therapy (bio-failure), no previous methotrexate use, and respiratory disease, while previous methotrexate use and absence of renal impairment or respiratory disease were associated with concomitant methotrexate therapy, and previous glucocorticoid use was associated with concomitant glucocorticoid therapy. The following associations were identified with regard to dose adjustment during treatment: bio-failure, no previous methotrexate use, previous csDMARDs use, presence of respiratory disease, allergy history, and higher CRP for golimumab dose escalation; shorter disease duration, previous GC, and no previous methotrexate use for methotrexate dose escalation; no prior biological therapy and renal impairment for methotrexate dose reduction; no previous GC use for glucocorticoid dose escalation; and absence of Steinbrocker's stage II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous csDMARDs use for glucocorticoid dose reduction. CONCLUSIONS: This study revealed that various baseline factors were associated with initiation of treatment and dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting both the treatment strategies of physicians for improving RA symptoms and/or reducing adverse events. FUNDING: Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.
29386902 Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis. 2018 Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients' individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given.
29526468 Long term effectiveness of RA-1 as a monotherapy and in combination with disease modifying 2018 Jul BACKGROUND: Data on long term use of Ayurvedic drugs is sparse. They may prove useful if combined with modern medicine in certain clinical situations (integrative medicine). We present the results of a long term observational study of RA-1 (Ayurvedic drug) used in the treatment of rheumatoid arthritis (RA). OBJECTIVE: The objective was to study safety of long term use of RA-1 for treatment of rheumatoid arthritis (RA). MATERIALS AND METHODS: On completion of a 16 week randomized controlled study, 165 consenting volunteer patients were enrolled into a three year open label phase (OLP) study. Patients were symptomatic with persistent active disease and naïve for disease modifying anti-rheumatic drugs (DMARD). 57 patients were on fixed low dose prednisone. Patients were examined every 10-14 weeks in a routine rheumatology practice using standard care norms. They continued RA-1 (Artrex ™, 2 tablets twice daily) throughout the study period and were generally advised to lead a healthy life style. Based on clinical judgment, rheumatologist added DMARD and/or steroids (modified if already in use) to patients with inadequate response; chloroquine and/or methotrexate commonly used. Treatment response was assessed using American College of Rheumatology (ACR) efficacy measures and ACR 20% improvement index standard update statistical software (SAS and SPSS) were used; significant at p < 0.05. RESULTS: 158, 130 and 122 patients respectively completed evaluations at 1, 2 and 3 year primary end point. The ACR 20 response (range 34-40%) remained stable over three years (p = 0.33). Patients improved optimum for several measures by one year (p < 0.05) and this was sustained. The use of steroids varied from 42 to 49% patients at yearly end points (mean daily dose 5 mg prednisone); correspondingly the use of DMARD varied from 20 to 34% patients. 40% patients on RA-1 did not require DMARD/steroids for control of disease. 77% patients reported adverse events, albeit mild and mostly gut related, and not causing withdrawal. Several study limitations (especially self-selection) were reduced by the high patient retention and consistency in drug use. CONCLUSION: RA-1 is safe and effective in the long term management of symptomatic active chronic RA. DMARDs and/or steroids can be used judiciously along with RA-1 to treat difficult disease/flares. Further studies are required to evaluate RA-1 in early RA. This paves way for research and application of integrative therapeutic approach in clinical medicine.
30186500 Tetrandrine alleviates symptoms of rheumatoid arthritis in rats by regulating the expressi 2018 Sep The present study aimed to construct a rat model of rheumatoid arthritis (RA) to evaluate changes in pathology, the expression of inflammatory factors and regulation of signaling pathways. The protective effect of tetrandrine (Tet) on tissue lesions induced by RA was also investigated. A total of 60 Wistar rats (100-200 g) were randomly divided into six groups (n=10 per group), namely a blank (NC) group, model group, methotrexate (MTX) group (3 mg/kg body weight), high-dose Tet group (31.25 mg/kg body weight), medium-dose Tet group (18.75 mg/kg body weight) and low-dose Tet group (6.25 mg/kg body weight). A rat model of RA was induced via injection of 0.1 ml complete Freund's adjuvant into the right rear toe. Toe swelling rate, arthritis index and immune organ index were calculated. In addition, cyclooxygenase (COX)-2 expression at the mRNA and protein level in the peripheral blood mononuclear cells (PBMCs) of rats were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Serum concentrations of inflammatory factors were measured using enzyme-linked immunosorbent assays. It was observed that treatment with Tet alleviated the severity of rear toe swelling associated with RA in rats. Furthermore, Tet exerted anti-inflammatory and immunosuppressive effects in the rat model of RA. Tet also reduced the expression of COX-2 in PBMCs and lowered the concentrations of inflammatory factors in the serum of RA rats. The present data indicate that Tet may exert pharmacological effects in the treatment of RA. The mechanism of action of Tet may be associated with the regulation of inflammatory factors and the inhibition of immune organs.
29692623 Nephritis, cerebritis, and myositis after adalimumab therapy in a patient with rheumatoid 2018 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mainly affects the joints, therefore, may cause deformities and disability if untreated. The first line of treatment is disease-modifying antirheumatic drugs (DMARDs). When the patient fails to respond to DMARDs, mainly methotrexate, then second-line therapy is required. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of RA; however, the treatment with anti-TNFα medications is challenging. It may trigger the autoimmune system and result in producing antibodies that induce symptoms and signs mimic to systemic lupus erythematosus (SLE), and in rare situations can affect vital organs with severe and life-threatening complications. We report on a 38-year-old Saudi woman with longstanding erosive RA, who was diagnosed based on the 1987 classification criteria. She developed life-threatening SLE, and seroconversion of antinuclear antibodies (ANA), anti-double-stranded DNA, with severe systemic involvement (cerebritis, nephritis, myositis, and polyneuropathy), shortly after treatment with adalimumab. Adalimumab was started as anti TNFa therapy (after the failure of traditional therapy), SLE and other autoimmune diseases were ruled out by clinical history, examination, and laboratory investigations, including negative ANAs and anti-double-stranded DNA. When both tests turned out persistently positive even after stopping adalimumab, specific diagnostic and therapeutic modalities were required during her acute illness.
31749869 Modulator role of infliximab and methotrexate through the transient receptor potential mel 2019 Oct INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients. MATERIAL AND METHODS: Neutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA). RESULTS: Intracellular free Ca(2+) concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca(2+) concentrations were further decreased by the ACA therapy. CONCLUSIONS: Our results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca(2+) concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.