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ID PMID Title PublicationDate abstract
30359668 A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a m 2018 Dec 28 As a potent macrolide immunosuppressant, cyclosporine A (CsA) is used to treat multiple autoimmune diseases, including non-autoimmune and autoimmune-mediated dry eye disease, rheumatoid arthritis and psoriasis. Despite its potency, CsA has poor solubility, poor bioavailability, and can cause serious adverse reactions such as nephrotoxicity and neurotoxicity. To overcome these limitations, we invented a new strategy to carry CsA by fusing its cognate human receptor, cyclophilin A (CypA), to a 73 kDa elastin-like polypeptide (ELP) termed A192 using recombinant protein expression. Derived from human tropoelastin, ELPs are characterized by the ability to phase separate above a temperature that is a function of variables including concentration, molecular weight, and hydrophobicity. The resultant fusion protein, termed CA192, which assembles into a dimeric species in solution, effectively binds and solubilizes CsA with a K(d) of 189 nM, comparable to that of endogenous CypA with a K(d) of 35.5 nM. The release profile of CsA from CA192 follows a one phase decay model with a half-life of 957.3 h without a burst release stage. Moreover, CA192-CsA inhibited IL-2 expression induced in Jurkat cells through the calcineurin-NFAT signaling pathway with an IC(50) of 1.2 nM, comparable to that of free CsA with an IC(50) of 0.5 nM. The intravenous pharmacokinetics of CA192 followed a two-compartment model with a mean residence time of 7.3 h. Subcutaneous administration revealed a bioavailability of 30% and a mean residence time of 15.9 h. When given subcutaneously for 2 weeks starting at 14 weeks in male non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis used to study Sjögren's syndrome (SS), CA192-CsA (2.5 mg/kg, every other day) significantly (p = 0.014) increased tear production relative to CA192 alone. Moreover, CA192 delivery reduced indications of CsA nephrotoxicity relative to free CsA. CA192 represents a viable new approach to deliver this effective but nephrotoxic agent in a modality that preserves therapeutic efficacy but suppresses drug toxicity.
28365217 Tropical arthritogenic alphaviruses. 2018 Mar Tropical alphaviruses have special tropism for bone and joint tissue. Patients can develop chronic rheumatic disorders similar to rheumatoid arthritis and ankylosing spondylitis. The prototype is Chikungunya virus, although other lesser known viruses in our environment such as Sindbis, Ross River, Mayaro, O'nyong nyong and Barmah Forest viruses have the potential to be sped through vectors and cause chronic rheumatic disease. International population movements have increased the numbers of patients diagnosed with these tropical viruses in areas in which they are not endemic. Since they can leave persistent symptoms and affect the quality of life of the patients, it is important that we be aware of them. Changes in ecosystems have favored the expansion of competent mosquitoes, making fears of local transmission in southern Europe a reality. The objective of this review is to provide a clinical approach to the different arthritogenic tropical alphaviruses, especially those in which chronic rheumatic disease is more frequent.
29361795 A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Adm 2018 Jan 22 A sensitive and rapid ultra high-performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin, daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active components in Zushima-Gancao extract. The analytes and internal standard (IS) were separated in a Hypersil Gold C(18) column and detected on a triple-stage quadrupole mass spectrometer using the validated method. All analytes exhibited good linearities (R² > 0.98), and the lower limit of quantification (LLOQs) were sufficient for quantitative analysis. Intra- and inter-batch precision were all within 14.96% while the accuracy of nine analytes ranged from -17.99 to 14.48%, and these results were all within acceptance criteria. The extraction recoveries, matrix effects, and stabilities were all satisfactory. Main pharmacokinetic parameters of each compound were compared, and significant differences were found in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last one, between the two groups. Therefore, adjuvant-induced arthritis has different effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The comparative pharmacokinetic study between normal and adjuvant-induced arthritis rats might provide more comprehensive information to guide the clinical usage of Zushima-Gancao extract for treating RA.
29570475 Tocilizumab in Giant Cell Arteritis. 2018 Nov/Dec Giant cell arteritis is a granulomatous immune-mediated vasculitis of medium and large vessels. It most commonly affects white females over the age of 50 and is the most common primary vasculitis in the United States. Treatment of this disease has classically been with high-dose corticosteroids, but this therapy has been associated with severe morbidity and mortality. Tocilizumab, a humanized monoclonal antibody targeting the interleukin-6 receptor, has been used with great efficacy and safety in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis. As interleukin-6 has been shown to be a key cytokine in giant cell arteritis, the use of an inhibiting agent has been explored. In the 15 case reports/series that were reviewed, most patients were given tocilizumab due to refractory giant cell arteritis and/or intolerance to glucocorticoid therapy, and most experienced remission of symptoms. At this time, there are only 2 randomized control trials to evaluate the efficacy and safety of tocilizumab use in giant cell arteritis. The phase II trial by Villiger et al and the GiACTA trial both showed that tocilizumab greatly increased the rate of sustained remission in giant cell arteritis over the course of 1 year. The most common adverse events were similar to those seen with use in rheumatoid arthritis: infections, neutropenia, and increases in lipids and liver function test enzymes. Based on the results of numerous case studies and the 2 randomized control trials, tocilizumab is the first agent to be approved by the Food and Drug Administration for treatment of giant cell arteritis.
35382152 Inflammatory arthritis in systemic sclerosis: What to do? 2019 Feb Musculoskeletal involvement, including arthritis and tendinopathy, is a common and important determinant of disability and impaired quality of life in systemic sclerosis. However, the treatment of arthritis in systemic sclerosis has not been studied as a primary outcome in randomized controlled trials, and arthritis-specific outcome measures for systemic sclerosis have not been sufficiently validated to date. Rheumatologists caring for patients with systemic sclerosis must address these complaints regularly despite the fact that the level of evidence for the treatment of systemic sclerosis-related inflammatory arthritis is limited. Consensus statements, based on treatments for related musculoskeletal aspects of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases, support the use of methotrexate and hydroxychloroquine. Newer biologics, which have efficacy in the treatment of other autoimmune conditions, may show promise in the treatment of arthritis in systemic sclerosis. In this article, we review the current literature on the assessment and treatment of systemic sclerosis arthritis in order to address management considerations.
30185372 Risk factor assessment of rheumatoid arthritis in North Kerala. 2018 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease; it leads to disabling and painful chronic inflammatory arthritis. Its onset may be delayed or even prevented by modifying the risk factors involved. Many genetic, epigenetic, and environmental factors are implicated in the pathogenesis of RA. The objectives of this case-control study were to assess various risk factors in our population and to compare the same with age- and sex-matched controls. METHODS: We studied 118 cases with RA diagnosed using the EULAR criteria. In total, 581 age- and sex-matched controls were selected. Each individual was administered a separate questionnaire regarding their risk factors (known risk factors were studied). The implicated dietary factors were incorporated in a food frequency questionnaire (FFQ) and administered to both cases and controls. Comparison was made between those who consume an item at a particular frequency, who consume less, and who consume nothing at all. Among those who consume, each group was re-compared. Statistical analysis was conducted using Statistical Package for Social Sciences (IBM Corp.; Armonk, NY, USA). RESULTS: There was significant relationship for family history, periodontitis, history of chikungunya, and sun exposure (p<0.05). Association with various food items was studied using the FFQ, but the relationship was inconsistent, probably due to consumption of modified diet by the persons with RA. Also, a majority of cases were females and nonsmokers for assessing an association with smoking habits. CONCLUSION: In our population, previous infections (e.g., chikungunya and poor oral hygiene with periodontitis) were the prominently observed risk factors. Also, smoking was less common among women, and probably contributed less, as majority of cases were females. For dietary pattern association, a prospective cohort study may be needed.
30389690 Tolerising cellular therapies: what is their promise for autoimmune disease? 2019 Mar The current management of autoimmunity involves the administration of immunosuppressive drugs coupled to symptomatic and functional interventions such as anti-inflammatory therapies and hormone replacement. Given the chronic nature of autoimmunity, however, the ideal therapeutic strategy would be to reinduce self-tolerance before significant tissue damage has accrued. Defects in, or defective regulation of, key immune cells such as regulatory T cells have been documented in several types of human autoimmunity. Consequently, it has been suggested that the administration of ex vivo generated, tolerogenic immune cell populations could provide a tractable therapeutic strategy. Several potentially tolerogenic cellular therapies have been developed in recent years; concurrent advances in cell manufacturing technologies promise scalable, affordable interventions if safety and efficacy can be demonstrated. These therapies include mesenchymal stromal cells, tolerogenic dendritic cells and regulatory T cells. Each has advantages and disadvantages, particularly in terms of the requirement for a bespoke versus an 'off-the-shelf' treatment but also their suitability in particular clinical scenarios. In this review, we examine the current evidence for these three types of cellular therapy, in the context of a broader discussion around potential development pathway(s) and their likely future role. A brief overview of preclinical data is followed by a comprehensive discussion of human data.
29459717 Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibr 2018 Feb 19 Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti-inflammation and anti-cancer properties. The present study was designed to investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis-related cells and collagen-induced arthritis (CIA) and further explore the potential underlying mechanisms. Our results showed that silibinin suppressed cell viability and increased the percentage of apoptotic RA-fibroblast-like synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model was effectively inhibited by silibinin. Silibinin also induced macrophage M2 polarization in RAW264.7 cells. We further demonstrated that silibinin inhibits Th17 cell differentiation in vitro. The nuclear factor kappa B (NF-κB) pathway was suppressed in RA-FLS. In addition, Sirtuin1 (SIRT1) was decreased after silibinin treatment, and RA-FLS transfection with a short hairpin RNA (shRNA) of SIRT1 enhanced silibinin-induced apoptosis. Autophagy was markedly decreased in a dose-dependent manner following silibinin treatment. These findings indicate that silibinin inhibited inflammation by inhibiting the NF-κB pathway, and SIRT1 may participate in silibinin-induced apoptosis. Silibinin also inhibited autophagy in RA-FLS. Thus, silibinin may be a potential therapeutic agent for the treatment of RA.
30225952 Psoriasiform skin eruption in a patient receiving certolizumab-pegol for ankylosing spondy 2018 Sep Certolizumab-pegol is the first and only pegylated TNF-α antagonist approved in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. We herein present a case of certolizumab-pegol induced generalized psoriasiform eruption in a patient with ankylosing spondylitis. The diagnosis was based on typical clinical and histopathological findings and further confirmed with Naranjo Adverse Drug Reaction Probability Scale which revealed a total score of nine supporting a definite causal relationship between the drug and skin eruption. As an important finding, a significant improvement of the generalized plaque lesions was achieved upon a therapy including high-potency topical corticosteroid and oral antihistamine without discontinuation of certolizumab-pegol. Moreover, we also present a literature review of the previously published cases with certolizumab-pegol induced psoriasiform eruption. Since all of these cases had Crohn's disease or rheumatoid arthritis as the underlying disease, this is the first case report of certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing spondylitis, to the best of our knowledge.
29848426 Spectrum of Joint Deformities in Children with Juvenile Idiopathic Arthritis. 2018 Jun OBJECTIVE: To determine the frequency and types of joint deformities in children with juvenile idiopathic arthritis and their association with clinical parameters and rheumatoid factor. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Rheumatology Outpatient Clinic, the Children's Hospital and the Institute of Child Health, Lahore, from September 2014 to February 2015. METHODOLOGY: All patients of both genders of less than 16 years of age, who fulfilled the International League of Association for Rheumatology (ILAR) criteria for Juvenile Idiopathic Arthritis (JIA), were enrolled in this study. Their demographic data, duration of disease at the time of presentation, types of JIA, various joint deformities and rheumatoid factor (RF) were documented. Statistical analysis of data was done on SPSS version 16. Chi-square test was applied to determine the association of clinical deformity with age of patients, disease duration at presentation, types of JIA and RF. RESULTS: Out of 70 patients enrolled during the study period, 51.4% were boys with mean age at presentation being 9.44 ±3.89 years (2-7 years) and median duration of disease being 24 months (interquartile range 42 months). Forty patients (57.1%) had joint deformities. Most common joints involved were hand (50%), wrist (50%), and knee (35.7%). The common types of joint deformities were boutonniere deformity (28.6%), ulnar deviation of wrist (28.6%), fixed flexion deformity of wrist (22.9%), and knee (31.4%). The most common type of JIA was polyarthritis RF negative with or without deformity. There was a strong association of deformities with older age of patients at presentation (p=0.036), longer duration of disease at presentation (p=0.028), polyarthritis (RF seronegative / seropositive) (p=0.013), and seropositivity (p=0.04). CONCLUSION: More than 50% patients with JIA have joint deformities. Joint deformities are more likely to be seen in children with long-standing disease, those with polyarthritis JIA and seropositive patients.
30554252 MIG in psoriatic arthritis. 2018 Nov Monokine induced by interferon (IFN)-γ (MIG) / chemokine (C-X-C motif) ligand 9 (CXCL)9 is involved in the pathogenesis of psoriatic arthritis (PsA). It was demonstrated that both blood plasma-derived dendritic cells (pDCs) and pDCs isolated from rheumatoid arthritis (RA) and PsA synovial fluid (SF), expressed CXC receptor (R) 3 and CXCR4, and that the chemotaxis of blood-derived pDCs is stimulated by MIG, (IFN)-γ-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T-cell α chemoattractant (I-TAC) )/CXCL11 and stromal cell-derived factor 1 (SDF-1)/ CXCL12, present in RA and PsA SF. In PsA patients have been found a Th1 immune predominance at early stage of disease, while a reduction of these chemokines has been observed in long lasting PsA, with a significant increase of monocyte chemoattractant protein-1/IP-10 ratio. This suggest a shift from Th1 to the Th2 immune response in long lasting PsA. High levels of MIG has been found in patients with PsA and autoimmune thyroiditis too. This chemokine has been proposed as a useful marker to monitor the activity as well the progression of PsA. Efforts have been made to modulate or prevent the production of MIG in PsA aiming to alter the course of the disease.
30886981 Perceptions of first-degree relatives of patients with rheumatoid arthritis about lifestyl 2018 BACKGROUND: There is increasing interest in the identification of people at risk of rheumatoid arthritis (RA) to monitor the emergence of early symptoms (and thus allow early therapy), offer lifestyle advice to reduce the impact of environmental risk factors and potentially offer preventive pharmacological treatment for those at high risk. Close biological relatives of people with RA are at an increased risk of developing RA and are therefore potential candidates for research studies, screening initiatives and preventive interventions. To ensure the success of approaches of this kind, a greater understanding of the perceptions of this group relating to preventive measures is needed. METHODS: Twenty-four first-degree relatives of patients with an existing diagnosis of RA from the UK, three from Germany and seven from Austria (age: 21-67 years) took part in semi-structured interviews exploring their perceptions of RA risk, preventive medicine and lifestyle changes to reduce RA risk. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Many first-degree relatives indicated that they anticipated being happy to make lifestyle changes such as losing weight or changing their diet to modify their risk of developing RA. Participants further indicated that in order to make any lifestyle changes it would be useful to know their personal risk of developing RA. Others implied they would not contemplate making lifestyle changes, including stopping smoking, unless this would significantly reduce or eliminate their risk of developing RA. Many first-degree relatives had more negative perceptions about taking preventive medication to reduce their risk of RA, and listed concerns about potential side effects as one of the reasons for not wanting to take preventive medicines. Others would be more willing to consider drug interventions although some indicated that they would wish to wait until symptoms developed. CONCLUSIONS: Information targeted at those considered to be at risk of RA should contain information about RA, the extent to which risk can be quantified at an individual level and how risk levels may differ depending on whether early symptoms are present. The benefits (and risks) of lifestyle changes and pharmacological interventions as potential preventive measures should be clearly described.
30139930 Retracted: miR-26a-5p Regulates Synovial Fibroblast Invasion in Patients with Rheumatoid A 2018 Aug 24 This paper is being retracted based on publishers' legal criteria. We have received notification from the author, Yonghui Shen, that he had added Dr. Wei Zhang (the first author) as a co-author fraudulently, without his permission or authorization, and that he falsified the confirmation from Dr. Zhang. Dr. Wei Zhang had no contribution to this paper.
29436996 Herbal Products for Common Auto-Inflammatory Disorders - Novel Approaches. 2018 BACKGROUND: Common auto-inflammatory disorders (CAIDs) constitute a wide array of ailments ranging from acute allergies to chronic conditions. Globally, CAIDs remain one of the leading causes of disability and morbidity. Despite playing a leading therapeutic role, the vast profusion of anti-inflammatory synthetic agents have not been able to fully resolve a panoply of CAIDs. Additionally, contemporary synthetic therapy approaches remain bounded by a wide array of limitations essentially being adverse effects and unaffordable costs. In this advent, the use of herbal products provides an interesting avenue to explore in view of developing such treatment regimens. OBJECTIVE: This review article endeavors to highlight potential herbal products and isolated phytochemicals which can be of benefit in the prophylaxis, management, and treatment alongside avoiding the relapse of CAIDs. CONCLUSION: This review article has highlighted that herbals, herbal products, and isolated metabolites hold a huge potential in the prophylaxis, management, and treatment of CAIDs. Herbals can act on various targets involved in the pathogenesis of inflammatory disorders. In addition, novel approaches for the management of CAIDs are numerous. Indeed, nanoparticles loaded with phytochemicals have been developed to specifically target the colon for IBD treatment. In silico approaches using herbals also offer unlimited avenues to decipher new pharmacophores. Investigating the potential of polyherbal formulations is another unique approach which can be investigated. Given the inefficacy of conventional medicines, the concomitant use of conventional and herbal medicines can also be explored.
28049394 Coexistance of Amyloidosis and Primary Sjögren's Syndrome: An Overview. 2018 BACKGROUND: The association of primary Sjogren´s Syndrome (SS) and amyloidosis has been recognized but scarcely assessed. OBJECTIVE: Herein we analyzed the literature regarding this association in order to describe a SS phenotype prone to both conditions. METHODS: PubMed and CINAHL databases were searched from inception until April 2016 for the keywords: Amyloidosis, amyloid, Sjögren's syndrome and their combinations. RESULTS: Most of the cases corresponded to localized amyloidosis mainly at skin and lung, whereas only three cases were systemic. Other places of localized amyloidosis were the kidney, tracheobronchial, tongue, breast, salivary gland and vocal cord. Most of the localized forms corresponded to AL type, whereas AA amyloidosis was uncommon. The diagnosis of amyloidosis followed the SS onset (1-25 years) and in the majority of patients the presence of B cell hyperactivity traduced by hypergammaglobulinemia, positive rheumatoid factor and/or anti-Ro/SSA and anti-La/SSB antibodies were observed. In seven patients, an associated lymphoma was also documented. CONCLUSION: The spectrum of lymphoid proliferation associated with SS extends beyond the classical B cell lymphoma. Localized or systemic amyloidosis might coexist with primary SS. Localized amyloidosis should be suspected in patients with consistently high serologic activity and suggestive lesions.
30093316 Oral lichenoid reactions may possibly be associated with abatacept: A case report and lite 2018 Nov Oral lichenoid reactions (OLRs) comprise a group of conditions with a common clinical appearance and histopathologic pattern that may be induced by several conditions or medications. This report describes an OLR possibly induced by a biologic agent. A 69-year-old woman with rheumatoid arthritis presented with a chief complaint of oral pain. The patient retroactively reported of skin lesions as well. Clinically, she had mixed red-white mucosal lesions and ulcers suggestive of an OLR. This diagnosis was supported by histopathologic findings. Withholding the putative etiologic agent, abatacept, resulted in immediate alleviation of both oral and skin lesions. Abatacept and other biologics are thought to help treat inflammation and are becoming more commonly prescribed to treat rheumatoid arthritis. However, the clinicians should explore these medications as a causative factor for OLR.
29862290 Are Janus Kinase Inhibitors Superior over Classic Biologic Agents in RA Patients? 2018 The Janus Kinases (JAKs) are a family of intracellular tyrosine kinases that provide transmission signals from cytokine, interferons, and many hormones receptors to the nucleus resulting in synthesis of many biologically active compounds and changing cell metabolism and function. That was theoretical background to synthetize the JAK inhibitors (Jakinibs). In recent years a substantial battery of evidence has been collected indicating the potential role of Jakinibs to interact with the specific elements of the immune system, therefore changing the inflammatory response. JAK kinase blockade offers a unique opportunity to block most of the key cytokines enabling the deep interaction into immune system functioning. Following discovery first Jakinibs were intensively studied in various forms of autoimmune diseases, including rheumatoid arthritis, and finally two Jakinibs tofacitinib and Baricitinib have been approved for the treatment of rheumatoid arthritis. Some clinical data indicated that under special circumstances Jakinibs may be even superior to biologics in the treatment of RA; however this suggestion should be verified in large clinical and observational studies.
30004047 Histopathological differences between primary Sjögren's syndrome and Sjögren's syndrome 2018 Jul BACKGROUND: Investigation of morphological differences in relation with serological variables between primary versus secondary Sjögren's syndrome associated with systemic scleroderma (Scl-SS). MATERIALS AND METHODS: A total of 69 primary Sjögren's syndrome (pSS) and Scl-SS patients were grouped according to the American-European Consensus Group criteria. Serum autoantibody information was obtained from the patient records. Hematoxylin and eosin sections of the minor salivary gland biopsy were reevaluated, and the lymphocyte focus score (FS), plasma cell focus, and fibrosis rates were all evaluated. RESULTS: There were 43 pSS and 26 Scl-SS cases. Both biopsy and autoantibody were positive in 16 pSS cases while only biopsy was positive in 25 cases and only antibody in 1 case. Both biopsy and antibody were positive in 5 Scl-SS cases while only biopsy was positive in 18 and only antibody in 3 cases. The plasma cell focus was statistically significantly higher in pSS cases (P = 0.003). No difference was seen between Sjögren' syndrome (SS) subtypes in terms of lymphocyte FS, fibrosis, and autoantibody positivity. CONCLUSION: We found that plasma cell focuses could be found more frequently in pSS than Scl-SS. In addition, our study reveals that the coexistence of SS and systemic scleroderma decreases the incidence of FS value ≥1 compared to pSS.
32186086 Effects of Xinfeng capsule on the Fas/FasL-mediated apoptotic pathway in patients with rhe 2018 Aug OBJECTIVE: To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis (RA). METHODS: A total of 28 RA patients were included in the study; they were randomly divided into the Xinfeng capsule (XFC) group (3 capsules, 3 per day) and the leflunomide (LEF) group (1 pellet, once per night). The treatment course in each groups was 12 weeks. The normal control (NC) group consisted of 10 healthy people. The apoptotic rate was examined using flow cytometry. Fas, FasL, caspase 8, caspase 3, bcl-2, and bax mRNA were examined using qRT-PCR. Apoptotic proteins Fas, FasL, caspase 8, and caspase 3 were examined using western blotting. RESULTS: After treatment, patients in the two groups all showed some trend of improvement. Disease activity indexes, joint morning stiffness time, joint swelling/tenderness number, health assessment questionnaire (HAQ) score, RA quality of life (RAQOL) questionnaire, and self-rating anxiety scale (SAS), as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between groups. But the improvement in terms of the self-rating depression scale (SDS) in the XFC group was better than in the LEF group. RA patients showed lower apoptotic rates in CD4+ T cells, lower bax, Fas, caspase 8, and caspase 3 mRNA, and less protein expression of Fas, caspase 8, and caspase 3 than in the NC group. These indicators increased after treatment. However, the level of Bcl-2 mRNA was higher in the XFC group than in the NC group before treatment, and it subsequently decreased. The XFC group expressed lower Bcl-2 mRNA than the LEF group. Negative correlations were found between ESR and the apoptotic rate in CD4+ T cells, Fas, and caspase 3; CRP and Fas; and, swollen joint count and Bax, while positive correlations were found between ESR and Bcl-2. CONCLUSION: XFC can regulate the Fas/FasL system and promote CD4+ T cell apoptosis and thus reduce the abnormal immune response, which can improve symptoms in RA patients.
30886952 Radiographic progression in early rheumatoid arthritis patients following initial combinat 2018 BACKGROUND: Early and intensive targeted treatment with disease modifying anti-rheumatic drugs (DMARDs) has been shown to lead to substantial reductions in disease activity and radiograph damage in patients with early rheumatoid arthritis (RA). The aim of this quasi-experimental study was to compare the first-year radiographic progression rates between a treat-to-target (T2 T) strategy with initial combination therapy (strategy II, started in 2012) versus an initial step-up monotherapy (strategy I, started in 2006). METHODS: A total of 128 patients from strategy II was individually matched with 128 patients from strategy I on sex, age (± 5 yrs.) and baseline disease activity (± 0.5 on the DAS28). Differences in radiographic progression (Sharp/van der Heijde) scores (SHS) and the number of patients experiencing a minimal clinically important difference (MCID; ≥ 5 SHS points) between both strategies were tested with Mann Whitney U and chi-square tests. Next, linear and logistic regression analyses were performed to examine which baseline variables were associated with radiographic progression scores and the probability of experiencing an MCID within 1 year. RESULTS: Patients with initial combination therapy had slightly higher baseline disease activity scores and pain scores, but better mental health scores. Patients with initial monotherapy had significantly more, and more frequently clinically relevant, radiographic progression after 1 year. Experiencing a MCID was independently associated with fewer tender joints (p = 0.050) and higher erythrocyte sedimentation rate (p = 0.015) at baseline. CONCLUSION: Treating early RA patients with initial combination therapy results in better radiographic outcomes than initial monotherapy in daily clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NTR578, 12 January 2006.