Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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30886977 | Resveratrol displays anti-inflammatory properties in an ex vivo model of immune mediated i | 2018 | BACKGROUND: Resveratrol is a natural polyphenol found in berries, roots and wine that is well known to have anti-inflammatory and anti-oxidative properties. The anti-inflammatory effect has been reported for both immune cells and connective tissues, but only few studies have investigated effects on immune mediated inflammatory arthritis. None of which have studied this effect when combining resveratrol with methotrexate or adalimumab, two major drugs in the treatment of immune mediated inflammatory arthritis.We therefore aimed to investigate the anti-inflammatory effect of resveratrol alone and in combination with methotrexate or adalimumab in ex vivo models of immune mediated inflammatory arthritis. We furthermore aimed to describe any variations in this effect based on disease activity and cellular composition of the synovial fluid infiltrate. METHODS: Synovial fluid mononuclear cells from patients with rheumatoid arthritis (n = 7) and spondyloarthritis (n = 7) were cultured for either 48 h or 21 days. In both models, synovial fluid mononuclear cells were treated with resveratrol alone or in combination with methotrexate or adalimumab. Monocyte chemoattractant protein 1, matrix metalloproteinase 3 and tartrate resistant acidic phosphatase were measured to quantify inflammation, enzymatic degradation and osteoclast differentiation, respectively. RESULTS: Resveratrol reduced monocyte chemoattractant protein 1 production by synovial fluid mononuclear cells significantly (p = 0.005) compared to untreated controls. The effect of resveratrol was greatest in cultures from patients with low disease activity, i.e. DAS28CRP ≤ 3.2 (p = 0.022), and in cultures dominated by lymphocytes (p = 0.03). Further, the combination of methotrexate and resveratrol significantly reduced monocyte chemoattractant protein 1 levels compared with methotrexate alone in cultures from patients with low disease activity (p = 0.016), and in cultures with high lymphocyte count (p = 0.011). Resveratrol did not significantly affect matrix metalloproteinase 3 and tartrate resistant acidic phosphatase production. CONCLUSION: Resveratrol has anti-inflammatory properties in our ex vivo model of immune mediated inflammatory arthritis. Results show an additive effect of resveratrol, when combined with methotrexate in samples dominated by lymphocytes and samples from patients with low disease activity. This suggests further investigations in vitro and whether this effect may also be present in a clinical setting. | |
31294239 | Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis. | 2018 | Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes. | |
30262983 | Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis. | 2018 | INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. MATERIALS AND METHODS: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA-untreated and MTX-treated cells were subjected to microarray analysis. RESULTS: Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples. DISCUSSION: The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with HSPA6, MMP1, MMP13, and TNFSF10 genes. CONCLUSIONS: The data from this study suggest the use of HSPA6, MMP1, MMP13, and TNFSF10 gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX. | |
29474901 | Arachidonic acid metabonomics study for understanding therapeutic mechanism of Huo Luo Xia | 2018 May 10 | ETHNOPHARMACOLOGICAL RELEVANCE: Huo Luo Xiao Ling Dan (HLXLD), a traditional Chinese medicine (TCM), is commonly used for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: To explore the potential therapeutic mechanism of HLXLD on anti-inflammatory activity. MATERIALS AND METHODS: A metabolomic approach based on UFLC-MS/MS to profile arachidonic acid (AA) metabolic changes was used. The cyclooxygenase (COX) and lipoxygenase (LOX) catalyzed metabolites in plasma were quantified on 7, 14, 21, and 28 days after the rats injected with Complete Freund's adjuvant and orally administrated with HLXLD, methotrexate and dexamethasone in parallel as the positive control drugs. RESULTS: Nineteen metabolites involved in COX and LOX pathways in RA model group were significant increased compared with normal group (P < 0.05), including 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, 8-HETE, leukotriene B(4)(LTB(4)), prostaglandin E(2) (PGE(2)), PGI(2), PGD(2), PGF(2α), thromboxane B(2) (TXB(2)), etc. From day 7 to day 28, the trajectory direction of HLXLD group and positive control groups gradually moved towards the initial space, and the concentrations of AA and its metabolites after HLXLD treatment were significantly reduced in dual pathways compared to control groups. CONCLUSION: HLXLD induced a substantial change in the AA metabolic profiles through refrain the expression of COX and LOX. The present investigation also highlights that distinct ingredients of this formula tend to inhibit different target to achieve a therapeutic effect. | |
28196776 | EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of th | 2018 Jan | OBJECTIVES: Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. METHODS: We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. RESULTS: In the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3±9.6 years from rheumatic disease onset and 58.7±47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2±24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed (P>0.05 in all comparison). CONCLUSIONS: The current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions. | |
29875847 | Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Metho | 2018 May 20 | AIM: This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). METHODS: In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. RESULTS: Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic progression comparing to the group of patients with monotherapy. CONCLUSIONS: Based on our results achieved during 2 years we can conclude that ETN in combination with MTX reduced disease activity, slowed radiographic progression and improved clinical manifestations more effectively than MTX alone. No serious adverse events were noticed in the group with combination treatment. | |
30622737 | Abatacept in combination with methotrexate in Japanese biologic-naive patients with active | 2018 | OBJECTIVES: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. METHODS: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. RESULTS: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. CONCLUSIONS: Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX. | |
29990853 | Evaluation of the effect of andrographolide and methotrexate combined therapy in complete | 2018 Oct | OBJECTIVE: Methotrexate is one of the most widely used disease-modifying anti-rheumatic drugs. The hepatotoxicity of methotrexate resulted in poor compliance with therapy. The current study was designed to analyse the combined therapy of andrographolide (AD) and methotrexate (MTX) for complete Freund's adjuvant (CFA)-induced arthritis, focusing on hepatoprotective effects, oxidative stress and arthritic-related cytokines. METHOD: Wistar rats were injected with CFA into the right hind paw. Ten days post-CFA injection, the Wistar rats were administered with 1% CMC-Na solution, methotrexate (2 mg/kg/week), AD (50 mg/kg/d) and combined therapy for 35 days. The anti-arthritic effect was assessed by paw volume, X-ray and serum tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β levels. Serum samples were also analysed for glutamic oxaloacetic transaminases (GOT), serum glutamic pyruvic transaminase (GPT), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH). Liver tissue samples were used to examine the cellular antioxidant defence activities using catalase activity (CAT) and GSH as well as GSH-Px and MDA. Histopathology analysis was conducted to evaluate liver damage. RESULTS: AD treatment strengthened the anti-arthritic capacity of MTX. AD and MTX-combined therapy additively reduced the inflammatory symptoms in CFA rats. The combined therapy of AD and MTX showed hepatoprotective effect indicated by an improvement in the serum marker, possibly due to antioxidant action and confirmed by liver histopathological changes. Furthermore, the combined therapy significantly reduced serum TNF-α, IL-6 and IL-1β levels. CONCLUSIONS: A combined therapy of AD and methotrexate significantly alleviated MTX-induced hepatocellular injury and strengthened the anti-arthritic effect. Further clinical studies should be done to further verify the possibility of combined its clinical usage. | |
28770639 | The preventive effects of nanopowdered red ginseng on collagen-induced arthritic mice. | 2018 May | This study was carried out to investigate the efficiency of red ginseng nanopowder in preventing collagen-induced arthritis (CIA) in mice. The mice were divided into five groups: normal group (no immunisation), control (CIA), powdered red ginseng (PRG), nanopowdered red ginseng (NRG) and methotrexate (MTX). Administering MTX, PRG and NRG to arthritic mice significantly decreased spleen indexes, clinical and histological scores compared to control group. Serum analysis of NRG and MTX groups showed a reduction in the cytokines such as the levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β) in comparison to PRG group. The levels of immunoglobulin M (IgM) and immunoglobulin G(1) (IgG(1)) in the NRG group were significantly lower than those of the PRG group. In summary, the present study indicated that NRG can be effective in preventing type II collagen-induced rheumatoid arthritis in mice. | |
29146737 | Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-c | 2018 Mar | OBJECTIVES: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. METHODS: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management. RESULTS: From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001). CONCLUSION: Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs. | |
30420888 | The Effect of Prednisone on Tuberculin Skin Test Reaction in Patients with Rheumatoid Arth | 2018 | OBJECTIVES: To assess the correlation between prednisone and methotrexate (MTX) treatment duration and dosage with the TST induration diameter of the TST reaction among rheumatoid arthritis (RA) patients. METHOD: We retrospectively analyzed consecutive cases of RA patients who were TNF-i therapy candidates. TST measurements, prednisone and methotrexate dosages, and treatment durations were recorded. A control group was randomly selected from healthy subjects. We compared TST reaction size between the following three groups: RA patients with current prednisone treatment, RA prednisone naïve patients, and healthy individuals. RESULTS: Our study sample comprised 43 RA patients with prednisone treatment, 22 prednisone naïve patients, and 195 healthy subjects. There was no significant difference in mean TST between the groups (5.3±6.6, 7.8±6.2, and 7.6±7.0, respectively, p=0.149). No correlation was noted between TST size and prednisone u-y (r=0.229, p=0.140) or methotrexate u-y in patients with and without prednisone therapy (r=0.219, p=0.158; and r=-0.293, p=0.186, respectively). CONCLUSIONS: Our results show that the TST reaction size among RA patients may not be affected by prednisone therapy. In addition, the TST reaction of RA patients may present similarly to that of healthy individuals. Therefore, we suggest that the criterion of a TST reaction of 5 mm to define latent TB infection in our population should be reevaluated. | |
30487994 | Novel methodology to discern predictors of remission and patterns of disease activity over | 2018 | OBJECTIVES: To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. METHODS: Phase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time. RESULTS: IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations. CONCLUSIONS: Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies. | |
30547379 | Use of Auto-Injector for Methotrexate Subcutaneous Self-Injections: High Satisfaction Leve | 2019 Mar | INTRODUCTION: The objective of the study was to compare compliance and acceptability of a new auto-injector (AI) versus syringe for administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: We conducted a randomized, open-label, parallel group study comparing AI to pre-filled syringe (PFS). Adult patients with RA (ACR/EULAR 2010) receiving MTX (orally or by injection) for at least 3 months were allocated to AI or PFS for 6 months and then were allocated to AI for 6 further months. Two co-primary endpoints were defined at M6: percentage of patients with compliance at least 80%; change in functional capacity assessed by Health Assessment Questionnaire (HAQ). Secondary endpoints included quality of life (RaQoL), RA activity (DAS28), and acceptability. Local safety at injection site was assessed at each visit. RESULTS: Two-hundred and sixty-five patients were randomized. The main analysis was conducted on per protocol set (99 AI and 98 PFS). Compliance was 96.2% in AI and 98.9% in PFS. Good complier rates were 89.9% and 94.9%, thus a difference of - 5.0% (- 18.9%; 8.9%). HAQ remained stable in both groups. No difference was found on RaQoL, change in RA activity, and safety profile. Autonomy, acceptability, and patient satisfaction were better with AI, and patients having had the experience of both AI and PFS preferred AI (p < 0.001). CONCLUSIONS: Although this study did not demonstrate non-inferiority of AI versus PFS, compliance was excellent in the two groups, and AI, which was preferred by patients, is a valuable alternative to PFS for administration of MTX. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02553018. FUNDING: Nordic Pharma SAS. | |
30343885 | In vivo imaging of activated macrophages by (18)F-FEDAC, a TSPO targeting PET ligand, in | 2018 Nov 17 | Rheumatoid arthritis (RA) is a chronic disease with systemic inflammation resulting in destruction of multiple articular cartilages and bones. Activated macrophage plays a pivotal role during the disease course and has been one of main targets to inhibit inflammatory reaction of RA by using biological disease-modifying anti-rheumatic drugs (bDMARDs). (18)F-FEDAC is one of PET imaging agents targeting TSPO, which is overexpressed in activated macrophages. The aim of this study was to evaluate the roles of (18)F-FEDAC PET as an in vivo imaging of activated macrophages on etanercept (ETN), a TNF-antagonist as one of bDMARDs in collagen induced arthritis mice. In RAW 264.7 cells, the expressions of TSPO as well as iNOS and infiltrated nucleus of NF-κB were induced by activation with lipopolysaccharide and interferon-gamma. TSPO expression was slightly attenuated by ETN treatment, not by methotrexate (MTX) as a cytotoxic agent. However, cell uptake of (18)F-FEDAC did not show significant changes according to both of the treatments. Similarly in CIA mice, (18)F-FEDAC uptake in inflamed paws on PET imaging did not show significant changes during both of the treatments, contrary to the uptake decrease of (18)F-FDG, a glucose analog to reflect metabolic or active inflammatory activity. Interestingly, when we divided joints according to the degree of (18)F-FEDAC uptake before ETN treatment, the joints of high (18)F-FEDAC uptake showed better response to ETN than the joints with low (18)F-FEDAC uptakes. In case of (18)F-FDG, there was no such kinds of patterns. We can speculate that (18)F-FEDAC PET imaging may identify activated macrophage-induced arthritis because that (18)F-FEDAC can reflect activated macrophages, which is the therapeutic target of ETN by TNF antagonistic effect. Thus, in vivo imaging using (18)F-FEDAC may be used as a predictor of therapeutic effects among those kinds of bDMARDs having anti-inflammatory actions to inhibit activated macrophage. | |
29554956 | Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: re | 2018 Mar 20 | BACKGROUND: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure. METHODS: Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks. RESULTS: A total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort. CONCLUSIONS: RF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment. | |
29380732 | Fulminant presentation of oral mucosal leishmaniasis as severe stomatitis and periodontiti | 2018 Jan | This case report shows an atypical presentation of mucosal leishmaniasis infantum in the oral cavity resulting in severe stomatitis and periodontitis. The patient was immunocompromised because of rheumatoid arthritis for which he used prednisone and methotrexate. He was treated with intravenous liposomal amphotericin B and recovered within four weeks. | |
28421999 | Use and withdrawal of immunosuppressors in primary Sjögren's syndrome. | 2018 May | OBJECTIVES: To assess the use and causes of withdrawal of glucocorticoids and immunosuppressors among patients with primary Sjögren's syndrome (pSS) in the clinical setting. METHODS: We retrospectively reviewed the medical records of 155 pSS patients and registered demographics, glandular/extraglandular features, serological data, cumulative ESSDAI and SSDDI. A single rheumatologist attributed the indication and cause of withdrawal of glucocorticoids and immunosuppressors. RESULTS: 92.2% of the patients were female, mean age 57.4±14.7 years and median follow-up 11 years. One hundred and four (67%) patients received glucocorticoids and/or immunosuppressors: 3.8% only glucocorticoids, 43.9% only immunosuppressors and 56.5% their combination. The most used drugs were antimalarials (46.4%), prednisone (36.7%), azathioprine (AZA) (23.8%) and methotrexate (MTX) (18%). At the multivariate analysis, the presence of non-erosive arthritis OR 5.02 (95% CI 1.74-14.47, p=0.003) and the median cumulative ESSDAI score OR 1.10 (95% CI 1.03-1.17, p=0.002) were associated with the use of these drugs. The causes of withdrawal were: 39% improvement, 35.2% patient's own decision, 18.1% toxicity and 11% lack of efficacy. We found toxicity in 14.2% MTX users, 9.7% for AZA, 9.7% for antimalarials and 7.6% for cyclophosphamide. CONCLUSIONS: More than half the patients received glucocorticoids and/or immunosuppressors and a not negligible number decided on their own to suspend them, alerting physicians of secondary adverse events and tolerability. | |
29208331 | Autoimmune and medication-induced lymphadenopathies. | 2018 Jan | This article will provide a discussion of some common autoimmune disorders that could affect the lymph nodes and potentially mimic B and T-cell lymphomas. Some of these disorders are more characteristic of individuals in the pediatric age group (autoimmune lymphoproliferative syndrome, Kawasaki disease), while others present in older individuals (rheumatoid arthritis, lupus erythematosus, sarcoidosis). A common finding that groups all of these disorders together is the overall relative preservation of the architecture, a feature that can be particularly helpful to distinguish them from many B and T-cell lymphomas. Another area of interest, that will be discussed in this review, is the pathologic manifestations that can be present in lymph nodes secondary to medications. Such alterations range from 'reactive' forms of follicular, interfollicular or paracortical hyperplasia, to specific B and T-cell lymphoproliferative disorders (particularly documented in association with methotrexate and TNF-inhibitors). | |
30185354 | Using subcutaneous methotrexate to prolong duration of methotrexate therapy in rheumatoid | 2018 Jul | OBJECTIVE: Our study aims to determine whether the use of subcutaneous methotrexate (SC MTX) is associated with prolonged MTX use and lower incidence of hepatotoxicity in rheumatoid arthritis (RA) patients on MTX monotherapy and multiple drug therapy. METHODS: We conducted a retrospective cohort study using national databases of a large hospital system. Subjects had been diagnosed with RA and treated with MTX between September 30, 1999, and October 1, 2009. Outcomes of interest were the amount of time on MTX monotherapy or multiple disease-modifying anti-rheumatic drug (DMARD) therapy before addition of additional DMARDs or biologic agents, respectively. We conducted Cox regressions and Kaplan-Meier curves for association between SC MTX use and length of time before therapeutic change. We conducted chi-square tests for association between SC MTX use and elevated liver function tests (LFT). RESULTS: MTX monotherapy: SC MTX was associated with a significantly lower likelihood of therapeutic change (HR 0.64, 95% CI 0.52-0.78). Multiple DMARD therapy: SC MTX was not associated with a lower risk of adding a biologic (HR 1.13, 95% CI 0.97-1.31). Liver enzymes: There was no significant association between use of SC MTX and decreased frequency of abnormal LFTs [p=0.09 for alanine aminotransferase (ALT), p=0.924 for aspartate aminotransferase (AST)]. CONCLUSION: Use of SC MTX is associated with longer duration of MTX monotherapy before addition of other DMARDs/biologic agents in RA patients. Use of SC MTX is not associated with significantly longer duration of multiple DMARD therapy before addition of biologic agents. Use of oral MTX is not significantly associated with increased frequency of elevated LFTs. | |
30185371 | Is rheumatoid arthritis an innocent bystander in female reproductive problems? A comparati | 2018 Sep | OBJECTIVE: Contrary to the old belief that rheumatoid arthritis (RA) is rare in sub-Saharan Africa, recent reports have increasingly recognized that the burden of the disease has probably been long under-appreciated in West Africa. Thus, fertility and other attributes of the reproductive lives among women with RA have not received research attention in Africa. We aimed to compare the fertility between married Nigerian women with and without RA. METHODS: A comparative study of 50 women with RA and 50 women without RA was conducted via the specialist rheumatology clinics at two teaching hospitals in Nigeria. The participants were aged 18 years or older. Patients with RA were recruited on the basis of the fulfillment of the 1987 American College of Rheumatology classification criteria for RA, whereas the control participants were age-matched to the patients. Using an interviewer-administered questionnaire, demographic and clinical information was collected from each participant. Clinical details at the time of diagnosis of RA were extracted from the hospital records of the patients. The patients were tested for rheumatoid factor and anti-cyclic citrullinated peptide antibody, and the disease activity was assessed using the Clinical Disease Activity Index. The functional status was determined using the Steinbrocker functional classification. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 20 (IBM Corp.; Armonk, NY, USA). The proportions of individuals with history of infertility, irregular menstruation, and menopausal states were compared between the two groups using χ(2) and Fisher's exact tests, whereas the durations of infertility and parities were compared using Mann-Whitney U and independent t-tests, respectively. RESULTS: A positive history of infertility was found in 22 (44%) patients and 14 (28%) controls (p=0.096), while 17 (34%) patients and 23 (46%) controls were found to be postmenopausal (p=0.221). History of irregular menstruation was present in 15 (30%) patients and 4 (8%) controls (p=0.005). The median duration of infertility was 60 (range: 16-132) months among the patients and 36 (range: 12-72) months among the controls (p=0.036), while the mean parity was 2.85±1.8 among the patients and 3.77±2.2 among the controls (p=0.027). A significant association was found between infertility and functional class as well as methotrexate treatment. CONCLUSION: Infertility is not uncommon among patients with RA, and like many aspects of rheumatic diseases, it may have been under-recognized in the Nigerian patients. |