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ID PMID Title PublicationDate abstract
25390810 Acute unilateral toxoplasma retinochoroiditis associated with adalimumab, a tumor necrosis 2013 Spring PURPOSE: The purpose of this study was to report a case of a patient with unilateral toxoplasma retinochoroiditis while on treatment with adalimumab, an anti-tumor necrosis factor α agent for ulcerative colitis. METHODS: This is a descriptive case report. RESULTS AND DISCUSSION: In addition to the patient with toxoplasma retinochoroiditis, there is one published report of two patients who developed toxoplasma chorioretinitis while on anti-tumor necrosis factor α therapy for rheumatoid arthritis: one was on adalimumab and methotrexate and the other one was on etanercept and methotrexate. CONCLUSION: The authors need to be aware of this potentially vision threatening risk with anti-tumor necrosis factor α therapy.
23395584 Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on cli 2013 Apr 3 Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p=0.42), seroprotection (83.3 vs. 72.2%, p=0.26) and FI-GMT (p=0.85). Disease duration, prednisone (2.1 ± 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p>0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p>0.05) and only mild side effects were reported in comparable rates to controls (p>0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p=0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p=0.0001) and anti-La/SSB (p=0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.
24493318 Spirometric evaluation in juvenile idiopathic arthritis: data from eastern India. 2014 Oct OBJECTIVE: To evaluate lung function in juvenile idiopathic arthritis (JIA) patients. METHODS: This was a case control study carried out at Institute of Post-Graduate Medical Education & Research, Kolkata, involving JIA patients between 5 and 12 y. They were diagnosed and classified on the basis of International League of Associations for Rheumatology (ILAR) criteria and compared with same number of age, sex, height and weight matched controls. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) and peak expiratory flow rate (PEFR) of cases were compared to those of matched controls. RESULTS: Among 36 JIA patients initially recruited, 9 were excluded. Of the remaining 27 patients, male: female ratio was 17:10. Mean age, height and weight of JIA patients were 9.15 y, 124.67 cm and 23.78 kg respectively. Six patients had oligoarthritis, 3 had rheumatoid factor positive (RF+) polyarthritis, 10 had rheumatoid factor negative (RF-) polyarthritis and 8 had systemic JIA. Eleven patients had active disease and 15 patients required methotrexate. None had respiratory symptoms. Mean duration of the disease was 2.96 y. Mean FVC and FEV1 were significantly less in JIA patients compared to controls (p value=0.0003 and 0.0007, respectively). FEV1/FVC in both the groups was similar (p value=0.96). Mean Z scores for FVC and FEV1 were significantly higher in JIA patients (p value=0.0064 and 0.0030, respectively). CONCLUSION: Spirometry in JIA patients demonstrated statistically significant restrictive pattern of alteration in pulmonary function.
23454555 Comparative efficacy of TACI-Ig with TNF-alpha inhibitor and methotrexate in DBA/1 mice wi 2013 May 15 The efficacies of TACI-Ig, rhTNFR:Fc and Methotrexate were compared in collagen-induced arthritis (CIA) mice. Sixty animals were divided into six groups: TACI-Ig (9 mg/kg), rhTNFR:Fc (4 mg/kg), Methotrexate (2mg/kg) and IgG-Fc (9 mg/kg) groups and were given medication for six weeks. Meanwhile, normal and CIA mice were given as control. The different efficacies of drugs were evaluated by the analyses of ankle joints and spleens pathology, cytokines, T and B lymphocytes subsets. TACI-Ig and rhTNFR:Fc reduced arthritis scores seven days later than that of Methotrexate. TACI-Ig and Methotrexate were superior to rhTNFR:Fc in reduction synovial hyperplasia and cell infiltration scores. The same result was observed for scores of spleens histopathology. TACI-Ig and Methotrexate presented higher efficacy than rhTNFR:Fc on B lymphocyte stimulator, but TACI-Ig was inferior to rhTNFR:Fc on TNF-alpha. TACI-Ig and Methotrexate could reduce significantly IgA and IgM, but rhTNFR:Fc had no effects on these immunoglobulins. TACI-Ig had more efficacy than rhTNFR:Fc in the decrease of CD4(+)CD154(+) T cell. TACI-Ig and Methotrexate also reduced CD4(+)CD69(+) T cell, rhTNFR:Fc had no effects on the T cell subset. TACI-Ig and Methotrexate were superior to rhTNFR:Fc on CD4(+)CD62L(+)T cells. TACI-Ig and Methotrexate could reduce CD19(+)IgD(+) and CD19(+)CD21(+) B cells, but rhTNFR:Fc had no obvious effect on above B cells subsets. TACI-Ig is as effective as rhTNFR:Fc and Methotrexate on CIA mice by ameliorating joint and spleen pathology, regulating T and B lymphocytes function, although different mechanisms among them. This study would be useful for treatment selection of rheumatoid arthritis in different pathological conditions.
25045858 Rapidly Fatal Internal Carotid Artery Mycotic Aneurysm Rupture in a Rheumatoid Patient Tak 2015 May OBJECT: Tumor necrosis factor (TNF)-α inhibitors are effective at treating certain inflammatory and autoimmune disorders. They are generally safe; potential adverse events include infections (bacterial, fungal, and viral), congestive heart failure exacerbations, and the potential for demyelinating diseases and possibly certain malignancies. We present the first documented case of fungal internal carotid artery (ICA) mycotic aneurysm in a patient being treated with a TNF-α inhibitor. We also review the literature on infections with TNF-α inhibition and the management of previously reported fungal ICA mycotic aneurysm cases. CASE DESCRIPTION: A 76-year-old woman with rheumatoid arthritis, treated with etanercept and methotrexate, presented with a 2-week history of left temporal headaches. She was treated empirically for giant cell arteritis (GCA) with oral prednisone, which provided no symptom relief. She was subsequently hospitalized for a superficial temporal artery biopsy, which was negative for GCA. She returned 2 weeks later after experiencing a left thromboembolic ischemic stroke. She had an acute neurologic decline, and a head computed tomography scan showed diffuse subarachnoid hemorrhage from a ruptured left fusiform paraclinoid ICA aneurysm. She was taken emergently for a craniotomy for clip-wrapping of the aneurysm, but intraoperative ultrasound revealed poor flow in the left anterior cerebral circulation and a complete infarct of the left-sided anterior circulation. The family withdrew care and the patient died. Postmortem analysis demonstrated fungi consistent with Aspergillus invading the necrotic left ICA. CONCLUSIONS: Although fungal mycotic aneurysms of the ICA are rare, their incidence may increase with the expanded use of immunosuppressive medications. Patients with rheumatoid arthritis who take potent immunosuppression regimens may be prime candidates for mycotic aneurysms because they often have two favoring conditions: atherosclerosis and immunosuppression. These ICA aneurysms carry a high mortality rate, so early diagnosis and aggressive therapy, potentially by endovascular trapping/vessel occlusion coupled with long-term antifungal therapy, is essential.
24000795 Genomic characterization of remission in juvenile idiopathic arthritis. 2013 Aug 30 INTRODUCTION: The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level. METHODS: Two independent cohorts of patients with JIA and healthy child controls were studied. RNA was prepared separately from peripheral blood mononuclear cells (PBMC) and granulocytes to identify differentially expressed genes using whole genome microarrays. Expression profiling results for selected genes were confirmed by quantitative, real-time polymerase chain reaction (RT-PCR). RESULTS: We found that remission in JIA induced by either methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX + Et) is characterized by numerous differences in gene expression in peripheral blood mononuclear cells and in granulocytes compared with healthy control children; that is, remission is not a restoration of immunologic normalcy. Network analysis of the differentially expressed genes demonstrated that the steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha (HNF4α) is a hub in several of the gene networks that distinguished children with arthritis from controls. Confocal microscopy revealed that HNF4a is present in both T lymphocytes and granulocytes, suggesting a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA. CONCLUSIONS: These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis.
23376792 Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells 2013 Mar Current therapies to treat autoimmune disease focus mainly on downstream targets of autoimmune responses, including effector cells and cytokines. A potentially more effective approach would entail targeting autoreactive T cells that initiate the disease cascade and break self tolerance. The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60(p216) and Qdm. We found that peptide-induced expansion of tetramer-binding CD8(+) Tregs that recognize Qa-1-Hsp60(p216) but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (T(FH)) and Th17 cells by CD8(+) Tregs inhibited disease development. Infusion of in vitro-expanded CD8(+) Tregs increased the efficacy of methotrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-1-Hsp60(p216)-specific CD8(+) Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60(p216) peptide immunization. These results suggest that strategies designed to expand Qa-1-restricted (HLA-E-restricted), peptide-specific CD8(+) Tregs represent a promising therapeutic approach to autoimmune disorders.
25281209 Patient participation in decisions about disease modifying anti-rheumatic drugs: a cross-s 2014 Oct 4 BACKGROUND: Involvement of patients in decision-making about medication is currently being advocated. This study examined (the concordance between) inflammatory arthritis patients' preferred and perceived involvement in decision-making in general, and in four specific decisions about Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Furthermore, this study examined how patients' involvement is related to satisfaction about decision-making and which factors are related to preferred roles, perceived roles and concordance. METHODS: Using a cross-sectional survey, 894 patients diagnosed with Rheumatoid Arthritis, Psoriatic Arthritis or Ankylosing Spondylitis were sent a questionnaire which focused on medical decisions in general and on four specific decisions: (a) starting with a traditional DMARD; (b) starting to inject methotrexate; (c) starting a biological DMARD; and (d) decreasing or stopping a DMARD. For each decision preferred and perceived involvement in decision-making was assessed using the Control Preference Scale. Concordance was calculated by subtracting the scores for perceived role from scores for the preferred role. Furthermore, satisfaction with the decision process and socio-demographic, health-related, patient-related and physician-related variables were assessed. RESULTS: The response rate was 58%. For all decisions, most patients (59%-63%) preferred Shared Decision-Making (SDM). SDM was perceived frequently (26%-55%) and patients' preferences were met in 54% of the respondents. Yet, in some specific decisions, 26% to 54% of patients would have liked more participation. Perceiving less participation then preferred was associated with less satisfaction with the decision-process, but perceiving more participation than preferred was not. Our results did not reveal any meaningful models to predict preferred or perceived participation in decision-making in general or with reference to specific decisions about DMARDs. CONCLUSIONS: Most arthritis patients prefer to be involved in decisions about their medication and SDM is perceived frequently. Yet, in some specific decisions patient participation can be further improved. Patients especially prefer more participation in decision-making regarding starting a first traditional DMARD, which occurs most commonly in newly diagnosed patients. Whereas perceiving too little participation was associated with decreased satisfaction, perceiving too much participation was not. Therefore, rheumatologists should urge patients to participate in every medical decision.
25034360 Etanercept: a review of its use in autoimmune inflammatory diseases. 2014 Aug With its approval more than 15 years ago, subcutaneous etanercept (Enbrel(®)) was the first biological disease-modifying antirheumatic drug (bDMARD) and the first tumour necrosis factor inhibitor to be approved for use in rheumatic diseases. Etanercept remains an important cost-effective treatment option in adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psoriasis, and in paediatric patients with juvenile idiopathic arthritis or plaque psoriasis. In all of these populations, etanercept (with or without methotrexate) effectively reduced signs and symptoms, disease activity and disability, and improved health-related quality of life, with these benefits sustained during long-term treatment. The safety profile of etanercept during short- and long-term treatment was consistent with the approved product labelling, with adverse events being of a predictable and manageable nature. The introduction of etanercept and other bDMARDs as therapeutic options for patients with autoimmune rheumatic diseases and spondyloarthropathies revolutionized disease management and these agents continue to have a central role in treatment strategies. This article reviews the extensive clinical experience with etanercept in these patient populations.
24184141 From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular di 2014 Jan BACKGROUND: Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD. OBJECTIVE: We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes. RESULTS: Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain. LIMITATIONS: Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor. CONCLUSION: Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies.
21801113 Leflunomide: dermatologic perspective. 2013 Apr Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug. It has successfully been used for the treatment of rheumatoid arthritis as a feasible alternative to methotrexate. Recently, leflunomide has been used in certain dermatologic conditions. Medline/PubMed search revealed only 201 articles of its application in dermatologic conditions, of which 21 were relevant for inclusion. Prime mode of action of leflunomide is through the inhibition of dihydroorotate dehydrogenase, a key enzyme in the de novo pyrimidine synthesis pathway used by lymphocytes for clonal expansion. The current level of evidence and strength of recommendation suggest its use in psoriasis and psoriatic arthritis. However, the use of leflunomide in severe atopic dermatitis, systemic lupus erythematosus, Wegener's granulomatosis, primary Sjögren's syndrome, bullous pemphigoid, dermatomyositis, sarcoidosis and systemic sclerosis still requires further evaluation.
24339395 Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune respons 2014 Jul OBJECTIVE: To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines. METHODS: We systematically searched the literature for studies evaluating the immune response to vaccines in RA patients receiving methotrexate (MTX) and/or biologic agents. The efficacy of vaccination, assessed by the response rate based on increased antibody titers before and 3-6 weeks after vaccination, was extracted by one investigator and verified by another. RESULTS: In total, 12 studies were included. RA patients mainly received MTX, anti-tumor necrosis factor α (anti-TNFα), or rituximab (RTX). Influenza vaccination response was reduced for RTX (43 patients; pooled odds ratio [OR] 0.44 [95% confidence interval (95% CI) 0.17-1.12] for H1N1, OR 0.11 [95% CI 0.04-0.31] for H3N2, and OR 0.29 [95% CI 0.10-0.81] for B) but not for anti-TNFα (308 patients; OR 0.93 [95% CI 0.36-2.37] for H1N1, OR 0.79 [95% CI 0.34-1.83] for H3N2, and OR 0.79 [95% CI 0.37-1.70] for B). For MTX, results differed depending on the method of analysis (222 patients; OR 0.35 [95% CI 0.18-0.66] for at least 2 strains, ORs were close to 1.0 in the single strain analysis). Pneumococcal vaccination response was reduced for 139 patients receiving MTX compared with controls (OR 0.33 [95% CI 0.20-0.54] for serotype 6B and OR 0.58 [95% CI 0.36-0.94] for 23F) but not for anti-TNFα (258 patients; OR 0.96 [95% CI 0.57-1.59] for 6B and OR 1.20 [95% CI 0.57-2.54] for 23F). For RTX, the response was reduced (88 patients; OR 0.25 [95% CI 0.11-0.58] for 6B and OR 0.21 [95% CI 0.04-1.05] for 23F). CONCLUSION: MTX decreases humoral response to pneumococcal vaccination and may impair response to influenza vaccination. The immune response to both vaccines is reduced with RTX but not with anti-TNFα therapy in RA patients.
24060529 Effect of tripterygium glycosides on pulmonary function in adjuvant arthritis rats. 2013 Dec BACKGROUND: Tripterygium is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis. Previous studies demonstrated that tripterygium glycosides (TPG) alleviated Freund's complete adjuvant (FCA)-induced arthritis. Simultaneously, it has also been observed to impact the adjuvant arthritis (AA) associated with lung injury. In this study, we have investigated whether traditional Chinese medicine could attenuate lung injury induced by AA by observing the effects of TPG on the degree swelling, arthritis index (AI), lung index (LI), pulmonary function, cytokines, and the expression of regulatory T cells (Treg) and Foxp3 in AA rats. METHODS: A total of 48 rats were separated into four groups: normal control (NC), model control (MC), methotrexate (MTX), and TPG groups (12 in each). Except for the rats of NC group, those in the others groups were intracutaneously injected in the right hind limb with 0.1 ml of FCA. The NC and MC groups were treated with physiological saline, and the MTX and TPG groups were treated with MTX and TPG, respectively. Thirty days after administration, the changes in swelling degree, AI, LI, pulmonary function, Treg levels, the ultrastructure of the lung tissue, and the expression of Foxp3 in the lung tissue were observed. RESULTS: Compared with NC group, the level of swelling degree, AI, LI, 1 second average expiratory flow (FEV1/FVC %), the alveolar inflammation integration, tumor necrosis factor alpha (TNF-α), and endothelium-1 (ET-1) in the MC group had significantly increased (p < 0.01). However, the level of forced vital capacity (FVC), 25% vital capacity of the peak expiratory flow (FEF25), 50% vital capacity of the peak expiratory flow (FEF50), 75% vital capacity of the peak expiratory flow (FEF75), maximum mid-expiratory flow (MMF), peak expiratory flow (PEF), interleukin-10 (IL-10), CD4(+) CD25(+) Treg, and Foxp3 had significantly decreased (p < 0.01). LI, the alveolitis score, and ET-1 were found to decrease with TPG treatment. However, the levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10 in serum, and CD4(+) CD25(+) Treg in peripheral blood had increased. The expressions of Foxp3 protein and mRNA in the lung tissue had also increased in the TPG group. Compared with the MTX group, the pulmonary function had enhanced, the structure of alveolar type II cells had improved, and the expression of the IL-10, Treg, and Foxp3 had elevated. However, the TNF-α and ET-1 levels had reduced as compared to the MTX group. CONCLUSION: The level of paw swelling and AI in the AA rats can be inhibited by TPG. The inflammatory response in lung tissue had also decreased, although there was significant improvement in the pulmonary function. The mechanism that would explain this observation is probably associated with the upregulation of the expression of IL-10, Treg, and Foxp3 and downregulation of the expression of TNF-α and ET-1.
25105206 Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive 2014 Nov OBJECTIVE: Treatment with tumour necrosis factor antagonists (anti-TNF) has been recognized as a risk factor for tuberculosis (TB) reactivation. Our aim was to evaluate risk of TB reactivation in rheumatologic and non-rheumatologic diseases treated with the same anti-TNF agents with and without concomitant therapies. METHODS: We searched for randomized controlled trials (RCTs) evaluating infliximab, adalimumab, and certolizumab in both rheumatologic and non-rheumatologic diseases until 2012. Results were calculated as pooled rates and/or pooled odd ratios (OR). RESULTS: Overall, 40 RCTs with a total of 14,683 patients (anti-TNF: 10,010; placebo: 4673) were included. TB reactivation was 0.26% (26/10,010) in the anti-TNF group and 0% (0/4673) in the control group, corresponding to an OR of 24.8 (95% CI 2.4-133). TB risk was higher when anti-TNF agents were combined with methotrexate or azathioprine as compared with either controls (24/4241 versus 0/4673; OR 54; 95% CI 5.3-88) or anti-TNF monotherapy (24/4241 versus 2/5769; OR 13.3; 95% CI 3.7-100). When anti-TNF was used as monotherapy, TB risk tended to be higher than placebo (2/5769 versus 0/4673; OR 4; 95% CI 0.2-15.7). CONCLUSIONS: TB risk with anti-TNF agents appeared to be increased when these agents were used in combination with methotrexate or azathioprine as compared with monotherapy regimen. TB risk seemed to be higher than placebo, even when monotherapy is prescribed.
25476830 Antinociceptive and anti-arthritic effects of kramecyne. 2015 Jan 15 AIMS: The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides. MAIN METHODS: The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effects of KACY on heat-induced hemolysis in rat erythrocytes were also evaluated. The in vivo anti-inflammatory assays were performed using the chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema and carrageenan-kaolin induced arthritis (CKIA). In the CKIA model, the hot plate test was performed, serum samples were obtained for the quantitation of pro-inflammatory (IL-1β, IL-6, IL-12 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines. KEY FINDINGS: KACY possess antinociceptive effects with comparable activity to naproxen (NPX). KACY inhibited hemolysis (EC50 = 180 μg/mL), in comparison to the untreated group and with a higher potency than NPX (EC50 = 263 μg/mL). KACY at 50 mg/kg decreased inflammation by 38% (chronic TPA-induced edema model) and by 26% (CKIA model), in comparison with the vehicle group and with similar activity to the positive controls 8 mg/kg indomethacin (IND) and 1 mg/kg methotrexate (MTX), respectively. In the CKIA model, KACY increased the release of anti-inflammatory (IL-4 and IL-10) cytokines but reduced the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α). KACY at 50 and 100 mg/kg showed antinociceptive effects by 27% and 23%, respectively, in mice with mono-arthritis. SIGNIFICANCE: KACY might be a good alternative for the treatment of rheumatoid arthritis (RA) due its antinociceptive and anti-inflammatory activities.
23363021 Possible antistenotic effect of tranilast in a patient with small bowel tuberculosis to pr 2013 May Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.
23580000 Regulation of inflammation by adenosine. 2013 Adenosine, a purine nucleoside generated by the dephosphorylation of adenine nucleotides, is a potent endogenous physiologic and pharmacologic regulator of many functions. Adenosine was first reported to inhibit the inflammatory actions of neutrophils nearly 30 years ago and since then the role of adenosine and its receptors as feedback regulators of inflammation has been well established. Here we review the effects of adenosine, acting at its receptors, on neutrophil and monocyte/macrophage function in inflammation. Moreover, we review the role of adenosine in mediating the anti-inflammatory effects of methotrexate, the anchor drug in the treatment of Rheumatoid Arthritis and other inflammatory disorders.
23291385 The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriat 2014 Jan BACKGROUND: The role of co-medication with tumour necrosis factor inhibitors (TNFi) is well established in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis (PsA) there is little evidence available on this issue. MATERIAL AND METHODS: The analyses were based on data from the Norwegian longitudinal observational study on disease-modifying antirheumatic drugs (NOR-DMARD). Patients with PsA starting their first TNFi, either as monotherapy or with concomitant methotrexate (MTX), were selected. Baseline characteristics, responses after 3, 6 and 12 months, and drug survival were compared between those with and without MTX co-medication. A secondary analysis was performed on patients who had confirmed swollen joints at baseline. Cox regression was used to identify predictors of discontinuation. RESULTS: We included 440 patients, 170 receiving TNFi as monotherapy and 270 receiving concomitant MTX. The groups had similar baseline characteristics, except for number of swollen joints, which was higher in the concomitant MTX group. Responses were similar in the two groups in both analyses. Drug survival analyses revealed a borderline significant difference in favour of patients receiving co-medication (p=0.07), and this was most prominent for patients receiving infliximab (IFX) (p=0.01). In the Cox regression analysis lack of concomitant MTX and current smoking were independent predictors of discontinuation of TNFi. CONCLUSIONS: We found similar responses to TNFi in patients with and without concomitant MTX, but drug survival was superior in patients receiving co-medication. The effect of MTX on drug survival was most prominent in patients receiving IFX. Smoking at baseline and use of TNFi as monotherapy were identified as independent predictors of drug discontinuation.
24566842 Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of pso 2014 Mar Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 % of patients with psoriasis will go on to develop PsA, usually within 5-10 years of cutaneous disease onset. Both conditions share common pathogenic mechanisms involving genetic and environmental factors. Because psoriasis is typically present for years before PsA-related joint symptoms emerge, dermatologists are in a unique position to detect PsA earlier in the disease process through regular, routine screening of psoriasis patients. Distinguishing clinical features of PsA include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as dactylitis and enthesitis. Patients with PsA are usually seronegative for rheumatoid factor, and radiographs may reveal unique features such as juxta-articular new bone formation and pencil-in-cup deformity. Early treatment of PsA with disease-modifying anti-rheumatic drugs has the potential to slow disease progression and maintain patient quality of life. Optimally, a single therapeutic agent will control both the skin and joint psoriatic symptoms. A number of traditional treatments used to manage psoriasis, such as methotrexate and cyclosporine, are also effective for PsA, but these agents are often inadequately effective, temporary in benefit and associated with significant safety concerns. Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and adalimumab, are effective for treating patients who have both psoriasis and PsA. However, a substantial number of patients may lose efficacy, have adverse effects or find intravenous or subcutaneous administration inconvenient. Emerging oral treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new biologics targeting interleukin-17, such as secukinumab, brodalumab and ixekizumab, have shown encouraging clinical results in the treatment of psoriasis and/or PsA. Active and regular collaboration of dermatologists with rheumatologists in managing patients who have psoriasis and PsA is likely to yield more optimal control of psoriatic dermal and joint symptoms, and improve long-term patient outcomes.
24062860 Perioperative management of patients with rheumatic diseases. 2013 This paper aims to explore the assessment of patients with rheumatologic diseases, especially rheumatoid arthritis (RA), before undergoing orthopedic surgery. Perioperative assessment ensures an early diagnosis of the patient's medical condition, overall health, medical co-morbidities, and the assessment of the risk factors associated with the proposed procedures. Perioperative assessment allows for proper postoperative management of complications and of the management of drugs such as disease-modifying anti-rheumatic drugs (DMARD) and anti-platelets, and corticosteroids. The assessment also supports follow up plans, and patient education. Perioperative assessment enables the discussion of the proposed treatment plans and the factors associated with them in each case among the different specialists involved to facilitate an appropriate early decision-making about the assessment and treatment of patients with rheumatologic diseases. It also enables the discussion of both condition and procedure with the patient to ensure a good postoperative care. The article identifies the components of perioperative medical evaluation, discusses perioperative management of co-morbidities and the management of specific clinical problems related to RA, systemic lupus erythematosus, the management of DMARDs, like methotrexate (MTX) and biologic therapies, prophylactic antibiotics, and postoperative follow up, including patient education and rehabilitation.