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ID PMID Title PublicationDate abstract
27803341 Adherence and Persistence with Methotrexate in Rheumatoid Arthritis: A Systematic Review. 2016 Nov OBJECTIVE: Medication adherence in patients with rheumatoid arthritis (RA) is typically suboptimal. Nonadherence has been associated with symptom worsening and increased disability. We systematically reviewed published clinical studies to evaluate methotrexate (MTX) adherence and persistence, factors associated with MTX adherence and persistence, and the effect of MTX nonadherence on clinical outcomes in RA. METHODS: MEDLINE and Embase were systematically searched (inception to February 2016) using relevant keywords. Observational or interventional clinical studies in patients with RA that specifically reported adherence to or persistence with MTX were included. Data were extracted using a predesigned, standardized template that included study design, patient demographics, and relevant outcomes. Main outcomes were MTX adherence and persistence rates in patients with RA treated with MTX and factors associated with MTX adherence and persistence. RESULTS: Of 365 references screened, 31 articles met inclusion criteria and another 10 were identified from searching reference lists. Estimates of MTX adherence varied from study to study because of heterogeneity in patient populations, duration of followup, definitions of adherence, and methods of assessment. Rates of MTX persistence ranged from 50% to 94% at 1 year and 25% to 79% at 5 years. No clear trends were identified in factors that influence MTX adherence and persistence. Two studies suggested that MTX adherence was associated with superior clinical outcomes. CONCLUSION: MTX adherence and persistence are highly variable in patients with RA. Research is necessary to determine the effect of nonadherence on health outcomes and to identify independent predictors of nonadherence to inform evidence-based interventions.
26624970 Sarcoidosis of the vagina treated with methotrexate. 2016 Jun We describe the first case of mediolateral episiotomic sarcoidosis of the deep vaginal tissue, without involvement of the pulmonary parenchyma or pulmonary symptoms. A 68-year-old female was admitted with a vaginal mass that had developed about 1 month prior. On bimanual examination, we found a painful solid mass approximately 4 cm in diameter on the episiotomy line of the deep vaginal tissue. The patient underwent pelvic magnetic resonance imaging on suspicion of a malignancy, and a vaginal true-cut biopsy was performed. The biopsy specimen exhibited non-caseating, granulomatous inflammation and many multinucleated giant cells, strongly suggesting sarcoidosis. We had excluded other granulomatous diseases; a final diagnosis was made of stage-1 sarcoidosis in the deep vaginal mass. A 3-month course of methotrexate (2.5 mg/week) was commenced to treat a flare-up of rheumatoid arthritis. The vaginal mass resolved. To the best of our knowledge, this is the first case of sarcoidosis in a deep vaginal mass without pulmonary parenchymal or other solid-organ involvement.
26212152 What's in a name? 2016 Jan A 51-year-old man with rheumatoid arthritis and diabetes mellitus presented with new onset left-sided hemiparesis, left-sided neglect, and left-sided incongruous, denser inferiorly, homonymous hemianopsia. Magnetic resonance image of the brain showed prominent swelling of the right frontal, parietal, and occipital lobes greater than on the left with significant change in the fluid-attenuated inversion recovery signal in the gray matter. Perinuclear antineutrophil cytoplasmic antibodies titers were elevated, and skin biopsy demonstrating leukocytoclastic vasculitis. He showed marked clinical and radiographic improvement in association with recovery of vascular abnormalities after the initiation of prednisone, pulse therapy with methylprednisolone, and methotrexate. Clinicians should be aware of the possibility of neuro-ophthalmic manifestations of rheumatoid arthritis, including rheumatoid arthritis-related vasculitis causing homonymous hemianopsia.
25939484 Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of 2016 Apr At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.
27233001 The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate 2016 Sep Methotrexate (MTX), the most commonly used anti-rheumatic drug against RA, enters the cell via the action of the reduced folate carrier 1(RFC1). A major polymorphism of the RFC1 gene, 80G/A, has been reported to influence the activity of RFC1, resulting in variable intracellular MTX-polyglutamate (MTX-PG) levels. However, the association studies addressing the RFC1 80G/A polymorphism and MTX efficacy or toxicity in Rheumatoid arthritis (RA) has yielded conflicting results. In the present meta-analysis, we aimed to evaluate the association between the RFC1 80G/A polymorphism and MTX efficacy or toxicity in RA patients. A total 17 studies met our inclusion criteria. Among them, 12 studies with 2049 subjects reported the association between the RFC1 80G/A and MTX response, and 12 studies involving 2627 subjects were on MTX-related toxicity. Meta-analysis revealed significant association between RFC1 80G/A polymorphism and MTX efficacy (odds ratio (OR) for the A allele=1.29, 95% confidence interval (CI) 1.05-1.67, P=0.02; for AA genotype: OR=1.49, 95%CI 1.17-1.907, P=0.001). However, no association could be detected in the analysis of MTX-related toxicity. Stratification by ethnic population also indicated an association between this polymorphism and MTX efficacy in Asian group (P=0.002 for A allele; P=0.003 for AA genotype), but not in the Caucasian group (P=0.15 for A allele; P=0.05 for AA genotype). In both Asian and Caucasian sub-groups, no influence of the RFC1 80G/A polymorphism on MTX toxicity can be detected. In conclusion, the RFC1 G80A polymorphism is associated with responsiveness to MTX therapy, but may not be associated with MTX toxicity in RA patients.
27711025 Methotrexate and lung disease in rheumatoid arthritis. 2017 Mar Rheumatoid arthritis (RA) is a common chronic inflammatory disease affecting many tissues and resulting in substantial morbidity and increased mortality. Arthritis is the most notable clinical feature, but extra-articular features can have devastating consequences. Pulmonary manifestations are common in RA, with high rates of disease related lung disease and a propensity to pulmonary infections. Respiratory illness remains a leading cause of death among RA populations. Modern medicine greatly reduces the illness burden among patients with RA, particularly through the use of disease-modifying medications. Methotrexate is recommended as the first-line treatment of RA as it effectively reduces disease activity, morbidity and mortality. However, it has long been implicated as a causative agent in lung disease. The evidence for a cause and effect relationship in modern populations is contentious, but critically important. Increasing recognition of the importance and prevalence of interstitial lung disease in RA, and recent studies on the incidence of lung disease among RA and non-RA populations have cast doubt on the role of methotrexate as a causative agent. A correct understanding of the complex pulmonary disease processes in RA is crucial if we are to improve outcomes in this patient group. In this article we will discuss the epidemiology and characteristics of lung disease in rheumatoid arthritis and its possible relationship to methotrexate use.
27856937 Allylpyrocatechol Attenuates Collagen-Induced Arthritis via Attenuation of Oxidative Stres 2017 Feb Rheumatoid arthritis (RA), an inflammatory autoimmune disorder, is characterized by synovial hyperplasia and bony destruction. The pathogenesis of RA includes redox dysregulation, concomitant with increased levels of proinflammatory mediators. As the ability of allylpyrocatechol (APC), a phytoconstituent of Piper betle leaves, to alleviate oxidative stress has been demonstrated in patients with RA, its antiarthritic activity was evaluated in an animal model of arthritis, and the underlying mechanism(s) of action clarified. The animal model was established by immunizing rats with bovine collagen type II (CII) followed by lipopolysaccharide, along with a booster dose of CII on day 15. Rats were treated with APC or methotrexate (MTX) from days 11 to 27, when paw edema, radiography, histopathology, and markers of inflammation were evaluated. The pro/antiinflammatory signaling pathways were studied in a RAW264.7 macrophage cell line. Allylpyrocatechol (APC) prevented the progression of arthritis as was evident from the reduction in paw edema, and attenuation of damage to bones and cartilage shown by radiography and histopathology. Additionally, there was reduction in the levels of proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] and restoration of the redox balance. Importantly, MTX ameliorated the features of arthritis but not the associated oxidative stress. In RAW264.7, APC inhibited generation of nitric oxide and proinflammatory cytokines (TNF-α, IL-6, and IL-12p40), and modulated the phosphorylation of proinflammatory (extracellular signal-regulated kinase 1/2, stress-activated protein kinase/c-Jun N-terminal protein kinase, and Janus kinase/signal transducers and activators of transcription) and cytoprotective (nuclear factor erythroid 2-related factor 2, heme oxygenase-1) signaling pathways. Taken together, APC controlled the development of arthritis, possibly via modulation of signaling pathways, and deserves further consideration as a therapy for RA.
26184955 Association of the ABCB1 C3435T polymorphism with responsiveness to and toxicity of DMARDs 2016 Sep OBJECTIVE: The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). METHODS: We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis. RESULTS: A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756-1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516-1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI  0.456-3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259-0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC). CONCLUSION: This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.
26585988 Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study 2016 Jun OBJECTIVES: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). METHODS: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. RESULTS: Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. CONCLUSIONS: Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. TRIAL REGISTRATION NUMBER: JapicCTI-101263.
27322646 Interleukin-6 (IL-6) Receptor Antagonist Protects Against Rheumatoid Arthritis. 2016 Jun 20 BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation. Flow cytometry was used to detect the ratio of CD4 naïve T cells and CD4 memory T cells, Th17 cells, and Treg cells in PBMC. DAS28 score, CRP, RF, and CCP levels in patients were evaluated. RESULTS Compared with before treatment, IL-6 receptor antagonist TCZ significantly improved patients' condition, including DAS28 score, CRP, RF, and CCP levels (P<0.01). Furthermore, TCZ obviously upregulated CD4 naïve T cells proportion and decreased CD4 memory T cells ratio (P<0.01). TCZ also markedly reduced the proportion of Th17 cells and increased the proportion of Treg cells (P<0.01). CONCLUSIONS TCZ can treat RA patients through regulating the ratio of CD4 naïve T cells, CD4 memory T cells, Th17 cells, and Treg cells in PBMC.
29933531 Effect of Sanhuangyilong decoction plus methotrexate on tumor necrosis factor alpha and in 2016 Oct OBJECTIVE: To investigate the effect of Sanhuangyilong decoction plus methotrexate (MTX) on Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the serum and synovial fluid of rheumatoid arthritis (RA) patients with damp-heat-obstruction symptom pattern, Sanhuangyilong decoction and the role of TNF-α and IFN-γ in the development of RA. METHODS: RA inpatients with damp-heat-obstruction symptom pattern (partly with knee joint effusion) were selected as the research subjects. Before the treatment, healthy subjects and osteoarthritis (OA) patients with knee joint effusion were assigned to the serum control group and the synovial fluid control group, respectively; during the treatment, RA patients with damp-heat-obstruction symptom pattern were divided into two groups: one is combined group that was administered Sanhuangyilong decoction plus MTX; the other group was MTX group that received MTX only. The expression levels of TNF-α and IFN-γ in the serum and synovial fluid were measured with enzyme-linked immunosorbent assay (ELISA) before and after the treatment, and the peripheral blood levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score in 28 joints (DAS28) were determined. RESULTS: Before treatment, the serum levels of TNF-α and IFN-γ in the RA patients with dampheat- obstruction symptom pattern were higher than those in healthy control group (P < 0.05).The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those in the serum of the RA patients (P < 0.05). The expression levels of TNF-α and IFN-γ in the synovial fluid of the RA patients were higher than those of the synovial fluid of the osteoarthritis patients (P < 0.05). The expression of TNF-α and IFN-γ in the serum and synovial fluid of the RA patients had no correlation with the inflammatory activity index ESR, CRP, or DAS28 (P > 0.05). After 2 weeks of treatment, the expression level of TNF-α and IFN-γ in the combined group had increased, although the difference was not statistically significant (P > 0.05); in contrast, ESR, CRP, and DAS28 decreased, and the difference was statistically significant (P < 0.01). After 4 weeks of therapy, TNF-alpha and IFN-γ, ESR, CRP, and DAS28 in the combined group decreased compared with the before-treatment levels (P < 0.01). After 2 w of treatment, the differences in the TNF-α and IFN-γ expression levels in the combined group were not statistically significant (P > 0.05) compared with that in the MTX group, although there were statistically significant differences in the ESR, CRP, and DAS28 (P < 0.05). After 4 weeks of treatment, differences in TNF-α, IFN-γ, ESR, CRP, and DAS28 in the combined group compared with MTX group were statistically significant (P < 0.01). CONCLUSION: TNF-α and IFN-γ might be involved in the development of RA. The RA patients with damp-heat-obstruction symptom pattern show better benefits from the treatment of Sanhuangyilong decoction plus MTX, and the treatment is superior to that of using MTX only.
26936261 Second-line therapy with biological drugs in rheumatoid arthritis patients in German rheum 2016 Aug The aim of the study was to assess the proportion of German patients with rheumatoid arthritis (RA) who received biological disease-modifying antirheumatic drugs (DMARDs) after initiation of conventional DMARD therapy. Patients aged 18 years or over who had initiated therapy with a conventional DMARD in a rheumatic care practice between 2009 and 2013 were included (IMS LRx database). The main outcome was the first prescription of a biological DMARD within 5 years following the index date. A multivariate Cox regression model was adopted to predict the prescription of biological DMARDs on the basis of patient characteristics. The mean age of the 137,673 patients with RA was 57.8 years (SD = 15.0). 68.3 % of the subjects were women. Most patients started their conventional DMARD therapy with methotrexate (62 %), sulfasalazine (13 %), and hydroxychloroquine (12 %). 20.7 % of the RA patients were given a biological DMARD within 5 years following the index date. Male gender was linked with a 10 % higher likelihood of biologic use whereas age decreased the odds of biological DMARD prescription by 3 % per year. Finally, leflunomide use was associated with increased odds of biologic prescription, whereas sulfasalazine and hydroxychloroquine decreased the chances of receiving biologics, as compared to methotrexate. Around 20 % of patients were being treated with biologics 5 years after prescription of conventional DMARDs. Gender, age, and initial treatment impacted the proportion of subjects treated with biological DMARDs.
26934454 Effectiveness of tacrolimus in comparison with methotrexate or biologics in propensity sco 2016 Nov OBJECTIVE: To analyze the effectiveness of tacrolimus (TAC) in comparison with methotrexate (MTX) or biologics in propensity score (PS)-matched rheumatoid arthritis (RA) patients. METHODS: RA patients with moderate or high disease activity as defined by the 28-joint disease activity score (DAS28) and who had completed at least two successive biannual RA cohort surveys were analyzed. Patients were assigned in a stepwise fashion to one of four groups (Biologics, MTX, TAC, or Control) according to medication changes during a 6-month period. A PS was generated for each of three conditions (Biologics, MTX or Control group versus the TAC group, respectively), followed by the assignment of PS-matched patients. At 1 year, the DAS28 in each treatment versus TAC group was analyzed using a mixed effect model with repeated measures. RESULTS: Compared with the respective PS-matched TAC group, the difference in DAS28 at 1 year was -0.398 [95% confidence interval (CI) - 0.660 to -0.136, p < 0.005] in the Biologics group (N = 120), -0.045 (95% CI -0.222 to 0.133, p = 0.622) in the MTX group (N = 465), and 0.182 (95% CI 0.010 to 0.353, p < 0.05) in the Control group (N = 462). CONCLUSION: TAC may provide a potential therapeutic option for RA patients with moderate to high disease activity.
27411429 Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumat 2016 Jul 13 BACKGROUND: Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). METHODS: PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta-analysis to compare different therapies by using frequentist approach. RESULTS: A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals. CONCLUSIONS: Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.
26719360 Repeat revascularisation outcomes after percutaneous coronary intervention in patients wit 2016 Mar OBJECTIVE: To investigate repeat revascularisation outcomes in patients with rheumatoid arthritis(RA) after percutaneous coronary intervention (PCI). METHODS: We performed a single-centre, retrospective matched cohort study of patients with RA matched to non-RA patients post PCI. Primary endpoints were time to target lesion revascularisation (TLR) and target vessel revascularisation (TVR) analysed by Cox proportional hazard shared frailty models. RESULTS: A total of 228 lesions (143 patients) were identified in the RA cohort and matched to 677 control lesions (541 patients). TLR occurred in 33% (n=75) of RA lesions versus 25% (n=166) of control lesions (adjusted HR 1.3; 95% CI 0.97 to 1.8). TVR occurred in 39% (n=89) of RA lesions versus 31% (n=213) of control lesions (adjusted HR 1.15; 95% CI 0.82 to 1.6). There was a significant hazard for TLR (adjusted HR 1.48; 95% CI 1.03 to 2.13) and TVR (adjusted HR 1.55; 95% CI 1.12 to 2.14) when excluding lesions with revascularisation events or follow-up less than 1 year. When stratified by treatment with methotrexate or tumour necrosis factor (TNF) α inhibitors or both at discharge, lesions from patients with RA treated with these agents had similar TVR and TLR as control lesions, whereas lesions from patients with RA not treated with these agents had significantly more TLR and TVR (TLR adjusted HR 1.48; 95% CI 1.08 to 2.03; TVR adjusted HR 1.38; 95% CI 1.04 to 1.84). CONCLUSIONS: RA predisposes to repeat revascularisation, specifically in patients followed after the 1-year landmark. In the absence of RA treatments including methotrexate and/or TNFα inhibitors, RA is associated with a 50% increased relative risk of repeat revascularisation following PCI. These findings emphasise the adverse effects of chronic inflammation on the durability of PCI and provide further support for aggressive anti-inflammatory treatment in patients with RA.
26139005 The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexat 2016 Jan OBJECTIVES: To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. METHODS: MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. RESULTS: 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. CONCLUSIONS: In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. TRIAL REGISTRATION NUMBER: (NCT01451203).
26899523 A Clinical Study Evaluating the Effects of Fluvastatin on Serum Osteoprotegerin Levels in 2016 Oct Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, has been identified as a critical regulator of bone resorption. Considering the possible role of OPG in rheumatoid arthritis (RA) and in the osteoclastogenesis suppression effects of statins, the present study aims to investigate the effects of fluvastatin on serum levels OPG and disease activity score (DAS) in patients with RA. Forty patients with RA were randomized in a placebo-controlled trial to receive 40 mg fluvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug (DMARD) therapy (methotrexate, leflunomide, hydroxychloroquine). Patients were followed up over 12 weeks. OPG and disease activity variables were measured at baseline and after 12 weeks of treatment. After 12 weeks, the OPG level was significantly increased in the fluvastatin group compared to the placebo group. DAS-28 was significantly decreased in the fluvastatin group compared to the placebo group. C-reactive protein (CRP), morning stiffness, swollen joint count (SJC), and tender joint count (TJC) were significantly decreased in the fluvastatin group compared to the placebo group; however, erythrocyte sedimentation rate (ESR), modified health assessment questionnaire (MHAQ), and visual analogue screen (VAS) were not changed significantly. In conclusion, fluvastatin administration could increase the OPG levels and improve disease activity variables in patients with RA. Therefore, fluvastatin may serve a potential benefit in the treatment of RA patients.
26238672 Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre-Specified Analysis of Two 2016 Mar OBJECTIVE: Anti-tumor necrosis factor (anti-TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti-TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. METHODS: A pre-specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment-emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week. RESULTS: A total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28-ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups. CONCLUSION: CZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy.
27661002 Evaluating radiocarpal cartilage matrix changes 3-months after anti-TNF treatment for rheu 2017 May PURPOSE: To evaluate the feasibility of MR T1ρ in assessing radiocarpal cartilage matrix changes following rheumatoid arthritis (RA) treatment. MATERIALS AND METHODS: Five healthy controls and nine RA patients were studied: three RA patients with low disease activity that were treated with methotrexate (MTX) alone and six with active disease despite MTX treatment who were additionally treated with certolizumab pegol, an anti-tumor necrosis factor biologic. Wrist 3 Tesla MRI were acquired at baseline and 3-month follow-up. T1ρ were quantified for lunar, radius, and scaphoid cartilage. Reproducibility was evaluated using coefficients of variation (CV). Longitudinal changes were evaluated with t-test and relationships between T1ρ with clinical, MRI, and patient-reported outcomes were evaluated with Spearman's rho. RESULTS: Scan/re-scan CVs of T1ρ values were all <5%, and intra- and inter-reader CVs were all < 2.0%. Baseline scaphoid T1ρ values were significantly higher in RA patients compared with healthy controls (P = 0.032). Changes in T1ρ (baseline, 3-month) were correlated with EULAR treatment response criteria: -2.26 ± 0.75 ms, 1.08 ± 0.52 ms, and 2.18 ± 0.45 ms for good, moderate, and nonresponders, respectively. Significant correlations were found between changes in global T1ρ values and changes in DAS28-CRP (r(s)  = 0.683; P = 0.042), MHQ (r(s)  = -0.783; P = 0.013), and HAQ (r(s)  = 0.833; P = 0.010). CONCLUSION: Despite the limited sample size and follow-up time points, there were significant correlations between changes in radiocarpal T1ρ and changes in disease activity as assessed by clinical and patient-reported outcomes. Our findings encourage further research into MR T1ρ assessment of RA disease activity and treatment response. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1514-1522.
25579963 Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for developme 2015 Mar The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds.