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ID PMID Title PublicationDate abstract
28676350 The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anh 2017 Nov Cytokines, including interleukin-6 (IL-6), modulate neuronal plasticity and stress coping. Depressive symptoms and major depressive disorder (MDD) have been associated with changes in cytokines and their signaling. The current study examined the effect of IL-6 monoclonal antibody administration on depressive symptoms in patients with rheumatoid arthritis (RA) or multicentric Castleman's disease (MCD). The data were obtained from two phase 2, double-blind, placebo-controlled trials designed to test the efficacy of sirukumab in RA (N=176) or of siltuximab in MCD (N=65), and were analyzed post hoc to investigate the effects of these IL-6 antibodies on depressive symptoms. The SF-36 questionnaire items on depressed-mood and anhedonia were combined as the measure for depressive symptoms. The study participants were grouped by the presence/absence of prevalent depressed mood and anhedonia (PDMA, meaning either depressed mood or anhedonia was present at least 'most of the time' and the other at least 'some of the time' for four weeks) at baseline; 26.1% of the RA sample and 15.4% of the MCD sample met criteria for PDMA at baseline. Compared with placebo, sirukumab and siltuximab produced significantly greater improvements on depressive symptoms. To account for an effect on mood due to changes in RA or MCD, the analysis was (1) adjusted for symptom severities using DAS28-CRP for RA and MCDOS for MCD alone or together with bodily pain and physical functioning, and (2) performed within RA and MCD non-responders. Improvement in depressive symptoms remained significant in the treated group for both drugs. The significance over placebo was also observed in the siltuximab study. The improvement in depressive symptoms by sirukumab correlated positively with the baseline soluble IL-6 receptor levels. The data together suggest that the IL-6 antibodies improve depressive symptoms in patients with RA and MCD. Further studies are needed to elucidate to what extents the IL-6 antibodies improve depressive symptoms through improving primary disease dependent and independent mechanisms, especially in RA patients, and the brain mechanisms underlying depressive symptom improvements.
27942777 Comparison of peripheral quantitative computed tomography forearm bone density versus DXA 2017 Apr Rheumatoid arthritis (RA) has been associated with osteoporosis. Quantitative computed tomography (QCT) is capable of assessing bone density and composition. We found lower bone density in RA compared to controls. Age and RA duration influenced bone density. QCT may be useful to assess bone metabolism in RA. INTRODUCTION: RA is associated with generalized and periarticular osteoporosis. In addition to DXA that determines areal bone mineral density (BMD), peripheral QCT also detects volumetric BMD. QCT differentiates between total, trabecular, and cortical BMD. Here, we compared DXA and QCT in RA patients and healthy controls. METHODS: BMD of 57 female RA patients and 32 age-matched healthy female controls were assessed by DXA. QCT of the forearm ultradistal region was also performed. Densitometry data were correlated with age, disease duration, disease activity, serum CRP, and anti-CCP levels. RESULTS: Total bone density (310.4 ± 79.7 versus 354.0 ± 54.1 mg/cm(3); p = 0.007) and attenuation (0.37 ± 0.05 versus 0.40 ± 0.03 1/cm; p = 0.001), trabecular density (157.6 ± 57.0 versus 193.8 ± 48.7 mg/cm(3); p = 0.005) and attenuation (0.28 ± 0.03 versus 0.32 ± 0.04 1/cm; p < 0.0001), and cortical density (434.3 ± 115.8 versus 492.5 ± 64.0 mg/cm(3); p = 0.006) and attenuation (0.44 ± 0.07 versus 0.47 ± 0.04 1/cm; p = 0.004) were significantly lower in RA. Both lumbar and femoral neck BMD, as well as T-scores, were significantly lower in RA versus controls (p < 0.001 in all cases). In RA, total and cortical QCT attenuation and density were associated with age, the presence of RA, and their combination. In contrast, trabecular density and attenuation were only affected by the presence of the disease but not by age. Also in RA, total trabecular and cortical density as determined by QCT significantly correlated with lumbar and/or femoral neck BMD as measured by DXA. Finally, anti-CCP seropositivity was associated with lower trabecular density and attenuation. CONCLUSIONS: Both DXA and QCT may be suitable to study bone metabolism in RA. Areal BMD determined by DXA may correlate with volumetric bone density measured by QCT. Moreover, trabecular osteoporosis may be associated by the underlying autoimmune-inflammatory disease, while cortical osteoporosis may rather be age-related.
28058962 Short-term effect of ultrasound-guided low-molecular-weight hyaluronic acid injection on c 2017 Nov To determine whether hyaluronic acid (HA) injection into rheumatoid arthritis ankles and feet can achieve improvement in foot function and reduce synovial hyper-vascularization. Forty-four patients with RA having unilateral or bilateral painful ankle and foot involvement (N = 75) were studied. All the patients were randomized to receive HA (N = 40) or lidocaine (LI) (N = 35) injection at 2-week intervals; Clinical assessments were performed using a visual analog scale (VAS) and foot function index (FFI(total)) including subscales of pain (FFI(pain)) before injection at baseline, 4 weeks (first evaluation) and 12 weeks (secondary evaluation). Imaging evaluation based on color Doppler ultrasound (CDUS) and synovitis scores was performed simultaneously. HA injection improved the VAS score (p = .009), FFI(pain) (p = .041), and FFI(total) (p = .032) considerably more than LI injections did at the first evaluation. The CDUS values at first evaluation (p = .005) and secondary evaluation (p < .001) decreased significantly compared with the base line values. HA injections reduced the CDUS values of more than half of the joints (54%, p = .042) while the control group exhibited no change (20%, p = .56). However, HA injection did not reduce the CDUS values more than LI injection did. Regarding the evaluation of synovial hypertrophy, no significant difference was observed between or within the groups in the synovitis scores. HA injection improved short-term foot function and pain reduction. HA injection may have a modest effect in reducing synovial hyper-vascularization. Further large-scale study is warranted to confirm this result.
28385457 Clinical meaning and implications of serum hemoglobin levels in patients with rheumatoid a 2017 Oct OBJECTIVE: Anemia is a common problem in rheumatoid arthritis (RA), associated with radiographic progression and disability. We explored the association of hemoglobin with a comprehensive set of variables in RA patients. METHODS: We included RA outpatients in the routine setting. For each patient we performed measurements (clinical measures, blood tests including serology, markers of acute phase response and iron metabolism, including hepcidin, and circulating hematopoietic precursor levels) at baseline and 12 weeks thereafter, and analyzed their changes in patients with a treatment adaptation at baseline. We performed principal component analysis (PCA) to identify thematic groups hemoglobin was related to. Then we constructed multivariable linear models to assess the contribution of individual variables to the variability of hemoglobin. RESULTS: In total, 88 patients were included (age: 58 ± 12; disease duration: 9.3 ± 9.6 years). Cross-sectionally (at baseline and week 12) hemoglobin levels were tied to iron metabolism and hematopoiesis, but not to clinical activity, based on thematic groups extracted from the PCA. In contrast, longitudinal changes in hemoglobin levels were closely linked to changes in clinical activity. Conversely, hepcidin reflected iron metabolism cross-sectionally, but changes in acute phase response longitudinally. In multivariable analysis variability components of hemoglobin were explainable by ferritin, ESR, evaluator global assessment (EGA), and iron levels, while components of hemoglobin changes were explained by changes in EGA mostly. Hepcidin was not independently associated with hemoglobin. CONCLUSION: Besides its dependence on body iron status, changes in hemoglobin levels are strongly tied to disease activity, possibly revealing more about disease activity than other laboratory markers.
29234875 Chronic disease list conditions in patients with rheumatoid arthritis in the private healt 2018 May INTRODUCTION: Little is known about the burden of rheumatoid arthritis (RA) in South Africa. The aim of this study was to establish the prevalence of RA and coexisting chronic disease list (CDL) conditions in the private health sector of South Africa. METHODS: A retrospective, cross-sectional analysis was performed on medicine claims data from 1 January 2014 to 31 December 2014 to establish the prevalence of RA. The cohort of RA patients was then divided into those with and those without CDL conditions, to determine the number and type of CDL conditions per patient, stratified by age group and gender. RESULTS: A total 4352 (0.5%) patients had RA, of whom 69.3% (3016) presented with CDL conditions. Patients had a median age of 61.31 years (3.38; 98.51), and 74.8% were female. Patients with CDL conditions were older than those patients without (p < 0.001; Cohen's d = 0.674). Gender had no influence on the presence of CDL conditions (p = 0.456). Men had relatively higher odds for hyperlipidemia (OR 1.83; CI 1.33-2.51; p < 0.001) and lower odds for asthma (OR 0.83; CI 0.48-1.42; p = 0.490) than women. In combination with hyperlipidemia, the odds for asthma were reversed and strongly increased (OR 6.74; CI 2.07-21.93; p = 0.002). The odds for men having concomitant hyperlipidemia, hypertension, type 2 diabetes mellitus and hypothyroidism were insignificant and low (OR 0.40; CI 0.16-1.02; p = 0.055); however, in the absence of hypothyroidism, the odds increased to 3.26 (CI 2.25-4.71; p < 0.001). CONCLUSION: Hypothyroidism was an important discriminating factor for comorbidity in men with RA. This study may contribute to the body of evidence about the burden of RA and coexisting chronic conditions in South Africa.
28286904 Short- and long-term mortality due to sepsis in patients with rheumatoid arthritis. 2017 Jun Severe infections and sepsis are common among patients with rheumatoid arthritis (RA) and are associated with increased morbidity and mortality risks. To determine whether RA is an independent risk factor for short- and long-term mortality in patients admitted to an Intensive Care Unit (ICU) with sepsis. A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR Registry, an ongoing study that collects data on all patients admitted with the diagnosis of sepsis to the ICUs of 7 large hospitals during the period 2002-2012. The primary outcomes of the study were the 30-day and 3-years survival rates. A total of 124 RA patients and 248 non-RA patients (mean age 71 years; 64.5% female) were included. Primary site of infection as well as pathogens distributions were similar between the two groups. Severe sepsis and septic shock were diagnosed in 92% vs. 84% (p = 0.03) and 50% versus 39% (p = 0.06) of the RA patients and non-RA, respectively. 30-day survival rates were similar between groups, whereas 3-year survival rate in 30-day survivors was significantly lower among RA patients (34.9%) compared to non-RA patients (55.7%) (p = 0.01). In multivariate Cox proportional hazards regression, RA was found to be a significant independent risk factor for 3-year mortality in 30-day survivors (hazard ratio 1.63 95% confidence interval 1.03-1.63; p = 0.04). RA is an independent risk factor for 3-year mortality, but not short-term mortality following ICU admission with sepsis.
27915033 Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid 2017 Mar MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms. This was associated with restricted pattern and low production of miRs. Additionally, miRNA processing enzymes Dicer and DGRC8 were decreased in the patients with survivin isoform spreading. The direct contribution of survivin in miRs biogenesis was confirmed by a massive increase of miRs production following inhibition of survivin in leukocyte cultures. Dicer is shown to mediate these effects of survivin. Chromatin immunoprecipitation analysis demonstrated binding of survivin to the Dicer promoter region. Dicer expression increased 5-folds following survivin inhibition. Taken together, this study presents experimental evidence of a novel cellular function of survivin, control of miRs biogenesis. Up-regulation of survivin in smokers suggests its role as effector of the adverse epigenetic control in RA.
28275210 Phytomedicine in Joint Disorders. 2017 Jan 16 Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.
29236711 Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicente 2017 The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63-1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55-1.45)), RAMRIS synovitis (0.85 (0.38-1.28)) and RAMRIS osteitis (0.99 (0.52-1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. (ClinicalTrials.gov registration: NCT01313520).
28132103 Polymorphisms in the multidrug-resistance 1 gene related to glucocorticoid response in rhe 2017 Apr A substantial proportion of rheumatoid arthritis (RA)-patients experience an insufficient response to glucocorticoids, an important therapeutic agent in RA. The multidrug-resistance 1 (MDR1) gene product P-glycoprotein (P-gp) is an efflux pump that actively transports substrates, such as glucocorticoids, out of the cell. We investigated if the variation in response might be explained by single-nucleotide polymorphisms (SNPs) in the MDR1 gene. RA-patients treated with intravenous methylprednisolone pulses (n = 18) or oral prednisone/prednisolone (n = 22) were included in a prospective cohort, and clinical response was measured after 5 and 30 days, respectively. The C1236T, G2677A/T, and C3435T SNPs were determined, and the functionality of P-gp was assessed by flow cytometry (Rhodamine efflux assay). Carriage of the G2677A/T SNP was significantly associated with response (OR = 6.18, p = 0.035), the other SNPs showed trends. Stratified for received treatment, the effect was only present in methylprednisolone treated patients. Mutant allele carriage significantly decreased functionality of P-gp in B cells, though had a smaller impact in other PBMC subtypes. Carriage of a MDR1 SNP was related to a response to methylprednisolone in this study, which his suggests that RA-patients carrying wild-type alleles might benefit from P-gp inhibition or administration of glucocorticoid analogues that are non-P-gp substrates.
28290136 Baricitinib: First Global Approval. 2017 Apr Baricitinib (Olumiantâ„¢) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. JAKs transduce intracellular signals from cell surface receptors for various cytokines and growth factors involved in inflammation and immune function, suggesting JAK inhibitors may be of therapeutic benefit in inflammatory conditions. In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Regulatory approval to market baricitinib as a treatment for RA has also been sought in the USA and Japan. This article summarizes the milestones in the development of baricitinib leading to this first global approval for the treatment for moderate to severe active RA in adult patients who have responded inadequately to, or are intolerant to one or more DMARDs.
29093340 Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model M 2017 Small interfering RNAs (siRNAs) are expected to offer a means of treating rheumatoid arthritis (RA) because they allow the specific silencing of genes related to RA pathogenesis. In our previous study, we reported that the siRNA targeted against RelA (anti-RelA siRNA), an important nuclear factor-kappaB (NF-κB) subdomain, was an effective therapeutic in atopic dermatitis and RA model animals. In this study, to develop an intra-articular injectable gel formulation against RA, we prepared a hydrogel that contains anti-RelA siRNA, and determined the in vitro release profile (%) and in vivo intra-articular retention of fluorescence-labeled model siRNA, and the anti-arthritic effects of the anti-RelA siRelA containing hydrogel in RA model mice. We selected the silk protein, sericin (SC), as an aqueous gel base, as it is a biocompatible and useful for forming hydrogels without a cross-linker. We showed that fluorescence-labeled model siRNA was continuously released from SC hydrogel in vitro, and retained in the knee joint of rats after injection of siRNA hydrogel. In addition, the knee joint thickness, clinical severity and incidence (%) in collagen-induced arthritis (CIA) mice as RA model treated with anti-RelA siRNA containing hydrogel were more improved than untreated, anti-RelA siRNA solution and negative control siRNA containing hydrogel group. Therefore, the intra-articular injectable sericin hydrogel formulation containing of anti-RelA siRNA could be a great potential therapeutic in rheumatoid arthritis.
29469725 Histiocytoid autoimmunity-related neutrophilic dermatosis in a patient with rheumatoid art 2017 Sep 15 Autoimmunity-associated neutrophilic dermatoses are a recently recognized manifestation of connective tissue diseases, in particular, lupus erythematosus. These entities are clinically and sometimes histopathologically distinct from classic neutrophilic dermatoses. We describe a case of an autoimmunity-related neutrophilic dermatosis in a patient with rheumatoid arthritis. In addition to this uncommon association, there was an absence of mature neutrophils and a population of immature histiocytoid granulocytes. This unusual case expands the concept of histiocytoid neutrophilic dermatoses to include those seen in association with autoimmune connective tissue diseases.
28217871 Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active C 2017 Jun OBJECTIVE: To evaluate the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to or intolerance of tumor necrosis factor (TNF) inhibitors. METHODS: In this phase III study, 551 patients were randomized (1:1:1:1) to receive intravenous secukinumab at a dose of 10 mg/kg (at baseline and weeks 2 and 4) followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks or, alternatively, abatacept or placebo on the same dosing schedule. The primary end point was the proportion of patients achieving 20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 24 in the secukinumab 150 mg or 75 mg treatment groups as compared with placebo. Key secondary end points included change from baseline to week 24 in the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) and the Health Assessment Questionnaire disability index (HAQ DI), as well as the ACR 50% improvement (ACR50) response rate at week 24. RESULTS: The primary efficacy end point was met in patients receiving 150 mg secukinumab, in whom the ACR20 response rate at week 24 was significantly higher than that in the placebo group. The ACR20 response rates at week 24 were 30.7% in patients receiving 150 mg secukinumab (P = 0.0305), 28.3% in those receiving 75 mg secukinumab (P = 0.0916), and 42.8% in those receiving abatacept, compared with 18.1% in the placebo group. A significant reduction in the DAS28-CRP was seen in patients treated with 150 mg secukinumab (P = 0.0495), but not in patients treated with 75 mg secukinumab. Improvements in the HAQ DI and ACR50 response rates were not significant in the 2 secukinumab dose groups compared with the placebo group. The overall safety profile was similar across all treatment groups. CONCLUSION: Secukinumab at a dose of 150 mg resulted in improvement in signs and symptoms and reduced disease activity in patients with active RA who had an inadequate response to TNF inhibitors. Improvements observed with abatacept were numerically higher than with secukinumab. There were no new or unexpected safety signals with secukinumab in this study.
28766398 Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a 2018 Mar OBJECTIVES: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis. MATERIALS AND METHODS: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10 mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis. RESULTS: A total of 18 female patients were enrolled in this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy group (n = 9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3 ± 2.3 cm(3); MTX monotherapy group: 2.4 ± 1.6 cm(3)); however, the difference was not significant. CONCLUSION: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.
29067885 A review article on biosimilar infliximab SB2 in the treatment of rheumatoid arthritis. 2017 Nov TNF inhibition has had a major impact as an approach for treating rheumatoid arthritis and a series of biologic agents directed against TNF have been developed for clinical use. Infliximab, a chimeric monoclonal antibody against soluble and membrane-bound TNF-α, was the biopharmaceutical to lead this 'biologics revolution'. However, with expiration of patent protection of the originator medicinal product, biosimilar versions of infliximab have been developed through biosimilarity studies and randomized controlled trials aiming to assess pharmacokinetic, pharmacodynamic and clinical equivalence to their originator (reference product) in patients with moderate-to-severe disease activity. This review summarizes the clinical development of SB2, a biosimilar of infliximab, in rheumatoid arthritis.
28957556 Rheumatoid arthritis patients with continued low disease activity have similar outcomes ov 2017 Oct 1 OBJECTIVES: To compare 10-year disease outcomes of RA patients who have continuous low disease activity and are on MTX with or without initial combination therapy with infliximab or prednisone and SSZ. METHODS: Recent-onset RA patients from the Behandel Strategieen (BeSt) (Dutch acronym for Treatment Strategies) study with 10 years of follow-up were analysed. Treatment was tightly controlled, targeted at DAS ⩽ 2.4. The selected patients had low disease activity from 6 months until 10 years and therefore did not intensify treatment. Patients were grouped into those receiving MTX monotherapy and those receiving initial combination therapy. Between-group differences over time were compared, using (generalized) linear mixed model analyses, for the outcomes DAS, HAQ, ESR, visual analogue scale patient global health, percentage of patients in (drug-free) remission and percentage of patients with Sharp/van der Heijde score progression ⩾5. RESULTS: At 10 years, 28/247 (11%) patients on MTX monotherapy (some tapered to drug free) had continued DAS ⩽ 2.4 compared with 68/261 (26%) patients on combination therapy (all tapered to monotherapy or drug free). No between-group differences in continuous responders were found over time, except for a higher percentage of patients in drug-free remission after MTX monotherapy. Significant group-time interactions were found for DAS, ESR and visual analogue scale patient global health, but the results seem clinically negligible. CONCLUSION: More patients achieved continuous low disease activity on initial prednisone or infliximab combination therapy than on initial MTX monotherapy, but there appeared to be no additional benefits. Regardless of induction therapy, patients with continuous low disease activity have similar long-term outcomes, with only a higher proportion of patients in drug-free remission after MTX monotherapy.
28573874 Role of mast cells in the induction of dry skin in a mouse model of rheumatoid arthritis. 2018 Mar PURPOSE: Rheumatoid arthritis (RA) is known to induce dry skin as an extra-articular symptom. However, the mechanisms behind the induction are unclear. In this study, we utilized an arthritis mouse model to simulate RA to reveal the relationship between arthritis and dry skin. MATERIALS AND METHODS: DBA/1JJmsSlc control mice (n = 5) and DBA/1JJmsSlc collagen-induced arthritis mouse model (arthritis mice; n = 5) were used. We measured transepidermal water loss (TEWL) and capacitance to reveal the effect of arthritis on skin barrier function. In addition, we measured the expression of biomarkers of skin barrier function. RESULTS: We found that the hind limb volume of the arthritis mice was higher than that of the control mice. Our results showed that the arthritis mice had higher TEWL and lower capacitance when compared to the control mice. When compared to that of the control mice, the skin of the arthritis mice was thicker with more leukocyte infiltration. In the skin of arthritis mice, we observed lower expression of type I and IV collagens, but higher expression of matrix metalloproteinases (MMP)-1 and -9 when compared to that of the control mice. The levels of mast cells, histamine, substance P, and tryptase were higher in the arthritis mice than in the control mice. This study showed that the arthritis mice exhibited a disruption of skin barrier function (i.e. dry skin), which was improved following treatment with a mast cell inhibitor. CONCLUSIONS: Our results on mast cells suggested that an improvement of dry skin is important for RA management.
27273801 Persistence With Conventional Triple Therapy Versus a Tumor Necrosis Factor Inhibitor and 2017 Mar OBJECTIVE: To compare persistence and adherence to triple therapy with the nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor (TNFi) plus MTX in patients with rheumatoid arthritis (RA). METHODS: Administrative and laboratory data were analyzed for US Veterans with RA initiating triple therapy or TNFi + MTX between January 2006 and December 2012. Treatment persistence 365 days postindex was calculated using 3 definitions. Definition 1 required no gap in therapy of ≥90 days for any drug in the original combination. Definition 2 required no added or switched DMARD, no decrease to nonbiologic DMARD monotherapy, and no termination of all DMARD therapies. Definition 3 was similar to definition 2 but allowed a switch to another drug within the same class. Adherence used a proportion of days covered of ≥80%. Propensity-weighted analysis with matched weights was used to balance covariates. RESULTS: The analysis included 4,364 RA patients (TNFi + MTX, n = 3,204; triple therapy, n = 1,160). In propensity-weighted analysis, patients in the TNFi + MTX group were significantly more likely than patients in the triple therapy group to satisfy all persistence criteria in definition 1 (risk difference [RD] 13.1% [95% confidence interval (95% CI) 9.2-17.0]), definition 2 (RD 6.4% [95% CI 2.3-10.5]), and definition 3 (RD 9.5% [95% CI 5.5-13.6]). Patients in the TNFi + MTX group also exhibited higher adherence during the first year (RD 7.2% [95% CI 3.8-10.5]). CONCLUSION: US Veterans with RA were significantly more likely to be persistent and adherent to combination therapy with TNFi + MTX than triple therapy with nonbiologic DMARDs.
28202019 Anti-arthritic property of crude extracts of Piptadeniastrum africanum (Mimosaceae) in com 2017 Feb 15 BACKGROUND: Rheumatoid arthritis, disease of unknown causes is a rheumatic and autoimmune pathology, recognised for its increasing frequency and its adverse consequences. It is a disease that occurs in most cases between 50 and 60 years and women are more affected than men. This study aimed at evaluating immunomodulatory and anti-arthritis capacity of aqueous and methanol extracts of stem bark of Piptadeniastrum africanum (Mimosaceae). METHODS: ROS production from phagocytes, proliferation of T-cells, TNF-α and IL-1β production and cytotoxicity were performed by using chemiluminescence technique, liquid scintillation counter, ELISA and MTT assay, respectively. Anti-arthritic activity was evaluated using a model of adjuvant induced arthritis. RESULTS: Methanol and aqueous extracts of Piptadeniastrum africanum significantly (P < 0.001) inhibited extracellular and intracellular ROS production. These extracts also possess significant (P < 0.001) inhibitory activity on T-cell proliferation other than reduced TNF-α and IL-1β production. Piptadeniastrum africanum also significantly exhibited antiarthritic activity in complete Freund's adjuvant induced arthritis in rat associated with a significant anti-inflammatory and anti-hyperalgesia activity. CONCLUSIONS: Immunomodulatory, anti-inflammatory, antihyperalgesia and anti-arthritis potential revealed in this study approve that, Piptadeniastrum africanum is a plant rich in compounds with anti-arthritic properties.