Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26986874 All-cause Mortality in Knee and Hip Osteoarthritis and Rheumatoid Arthritis. 2016 Jul BACKGROUND: While increased mortality in rheumatoid arthritis (RA) is well established, there is conflicting evidence on the association between osteoarthritis (OA) and mortality. Our aim was to estimate all-cause mortality in Swedish patients with RA and OA compared with the general population. METHODS: Cohort study of the population of Skåne region, Sweden (1.3 million), based on physicians' diagnostic codes in a mandatory register covering all health care. We included all subjects aged ≥45 years who between 1998 and 2012 consulted any physician at least once. We identified those who received a diagnosis of RA, knee OA, or hip OA. We followed all subjects until death, relocation outside Skåne region, or end of 2013, and analyzed data using Cox proportional hazard regression with attained age as time scale. RESULTS: We identified 8,067 patients with RA, 51,939 with knee OA and 29,442 with hip OA among 524,136 in the population aged ≥45 years. The mortality rates adjusted for sex, socioeconomic status, and comorbidities were elevated for RA, hazard ratio 1.86 (95% confidence interval = 1.78, 1.94) but not in knee or hip OA compared with the general population seeking health care, hazard ratio 0.87 (0.85, 0.89) and 0.90 (0.87, 0.92), respectively. Extensive sensitivity analyses supported the conclusion of no increased mortality in OA. CONCLUSIONS: In Sweden, RA is associated with about doubled mortality rate, but we found no increased mortality in patients with knee and hip OA. Possible selection of those seeking physician care for knee or hip pain and/or OA management in health care are plausible explanations.
27618867 Impact of early diagnosis on functional disability in rheumatoid arthritis. 2017 Jul BACKGROUND/AIMS: To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. METHODS: A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. RESULTS: A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). CONCLUSIONS: Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration.
25737174 Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in 2015 Mar OBJECTIVES: To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors. METHODS: Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs was almost the same among Saudis and non-Saudis with no significant difference (p>0.05) for each DMARD; MTX was the most commonly used DMARD (71-76%). RESULTS: There was no association between anti-MCV positivity and different DMARDs use. Methotrexate was used 76 times as combination, scoring the highest in this respect. There was a significant correlation (p<0.05) between Plaquenil with Methotrexate and with Sulfasalazine; Leflunomide with anti-TNF and with Prednisolone; age with Methotrexate and with Plaquenil; anti-MCV positivity with Prednisolone. Saudi/non-Saudi status showed no correlation with all factors or drugs. There was no significant association between DMARDs and comorbidity. CONCLUSION: Similar to worldwide results, MTX was the most commonly used DMARD; with the addition of anti-TNF to increase the effect, and folic acid to minimize the side effects. In this cohort, the pattern of use for all DMARDs was similar among Saudis and non-Saudis; treatment depended neither on anti-MCV positivity nor on the presence of comorbid conditions. A study of the association of DMARDs with disease activity is recommended.
25648267 Secukinumab: first global approval. 2015 Feb Secukinumab (Cosentyxâ„¢) is a fully human monoclonal antibody against interleukin-17A, formulated for intravenous and subcutaneous administration. It received its first global approval in Japan on 26 December 2014 for the treatment of psoriasis and psoriatic arthritis in adults who are not adequately responding to systemic therapies (except for biologic agents). In the USA and the EU, secukinumab was approved in early 2015 for the treatment of patients with moderate-to-severe plaque psoriasis. Secukinumab is also being investigated in patients with ankylosing spondylitis and rheumatoid arthritis. This article summarizes the milestones in the development of secukinumab leading to its first approval for the treatment of adult patients with psoriasis and psoriatic arthritis.
25649885 Immunoglobulin and CD8⁺ T-cell distribution in histologically distinctive tonsils of ind 2015 Mar CONCLUSION: This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection. OBJECTIVES: Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection. METHODS: Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis. RESULTS: The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.
26090487 GDF15(MIC1) H6D Polymorphism Does Not Influence Cardiovascular Disease in a Latin American 2015 OBJECTIVE: Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. METHODS: This was a cross-sectional analytical study in which 310 consecutive Colombian patients with RA and 228 age- and sex-matched controls were included and assessed for variables associated with CVD. The mixed cluster methodology based on multivariate descriptive methods such as principal components analysis and multiple correspondence analyses and regression tree (CART) predictive model were performed. RESULTS: Of the 310 patients, 87.4% were women and CVD was reported in 69.5%. Significant differences concerning GDF15 polymorphism were not observed between patients and controls. Mean arterial pressure, current smoking, and some clusters were significantly associated with CVD. CONCLUSION: GDF15 (rs1058587) does not influence the development of CVD in the population studied.
27036380 Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthri 2016 Jun OBJECTIVE: The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA development were studied. METHODS: Whole blood samples from newly diagnosed, treatment-naive, seropositive (SP) and seronegative (SN) patients with RA (SP RA, n = 45 and SN RA, n = 12), patients with SP arthralgia (n = 30), and healthy controls (HC, n = 41) were assessed for numbers and frequencies of T cells, B cells, and NK cells. SP status was defined as positive for anticyclic citrullinated peptide antibodies (anti-CCP) and/or rheumatoid factor (RF). Peripheral blood mononuclear cells were used for further analysis of NK cell phenotype and function. RESULTS: Total NK cell numbers were decreased in SP RA and SP arthralgia but not in SN RA. Also, NK cells from SP RA showed a decreased potency for interferon-γ (IFN-γ) production. A selective decrease of CD56(dim), but not CD56(bright), NK cells in SP RA and SP arthralgia was observed. This prompted investigation of CD16 (FcγRIIIa) triggering in NK cell apoptosis and cytokine expression. In vitro, CD16 triggering induced apoptosis of CD56(dim) but not CD56(bright) NK cells from HC. This apoptosis was augmented by adding interleukin 2 (IL-2). Also, CD16 triggering in the presence of IL-2 stimulated IFN-γ and tumor necrosis factor-α expression by CD56(dim) NK cells. CONCLUSION: The decline of CD56(dim) NK cells in SP arthralgia and SP RA and the in vitro apoptosis of CD56(dim) NK cells upon CD16 triggering suggest a functional role of immunoglobulin G-containing autoantibody (anti-CCP and/or RF)-immune complexes in this process. Moreover, CD16-triggered cytokine production by CD56(dim) NK cells may contribute to systemic inflammation as seen in SP arthralgia and SP RA.
26727655 Doubling the single-dose infusion rate of tocilizumab in rheumatoid arthritis is safe and 2016 Jul OBJECTIVES: To investigate the impact of enhanced infusion rate of tocilizumab on the occurrence of infusion reactions, overall safety, and efficacy in rheumatoid arthritis (RA). METHOD: We conducted a 24-week multicentre, open-label, randomized parallel group study comparing adverse event (AE) and effect profiles following tocilizumab IV 8 mg/kg every 4 weeks over 31 min vs. standard 60-min infusions in patients with RA and an inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-α inhibitors. RESULTS: A total of 47 patients were enrolled in the study and randomized to fast infusions (n = 25) and controls (n = 22). Incidences of infusion reactions were similar between the two groups, neither of them leading to withdrawal. Likewise, the incidence of additional AEs did not differ between the treatment arms. Two serious adverse events (SAEs) were reported, in the control group. Four patients withdrew due to AEs, two from each arm. Efficacy at week 24 was comparable between groups. CONCLUSIONS: In RA, monthly tocilizumab infusions of 8 mg/kg provided over 31 or 60 min during 24 weeks did not differ concerning safety or efficacy.
25847183 Development and validation of panoptic Meso scale discovery assay to quantify total system 2015 Oct AIM: Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms ranging from a low molecular weight (MW 20-30 kDa) non-complexed form to high MW (200-450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to understand clinical responses to IL-6-targeted treatments. Existing assays measure only the low MW, non-complexed IL-6 form. The present work aimed to develop a validated assay to measure accurately total IL-6 (complexed and non-complexed) in serum or plasma as matrix in a high throughput and easily standardized format for clinical testing. METHODS: Commercial capture and detection antibodies were screened against humanized IL-6 and evaluated in an enzyme-linked immunosorbent assay format. The best antibody combinations were screened to identify an antibody pair that gave minimum background and maximum recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6 assay was developed and transferred to the Meso Scale Discovery (MSD) platform for large scale clinical testing. RESULTS: The top-performing antibody pair from 36 capture and four detection candidates was validated on the MSD platform. The lower limit of quantification in human serum samples (n = 6) was 9.77 pg l(-1) , recovery ranged from 93.13-113.27%, the overall pooled coefficients of variation were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis patients, were detected by the assay but not by a commercial kit. CONCLUSION: This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and low MW forms may have clinical utility.
27709770 Health Professionals' Perceptions of the Effects of Exercise on Joint Health in Rheumatoid 2017 Sep OBJECTIVES: Although exercise is an important factor in the management of rheumatoid arthritis (RA), research indicates that patients perceive that health professionals (HPs) are uncertain about the place of exercise in treatment and its relationship with joint damage. The present study investigated the perceptions of HPs regarding the effects of exercise on joint health in RA patients. METHODS: A questionnaire investigating perceptions of exercise and joint health was distributed via professional networks and websites. Confirmatory factor analysis (CFA) was used to analyse questionnaire data and develop a focus group interview guide. Focus groups were conducted with multidisciplinary teams (MDTs) of rheumatology HPs and analysed using framework analysis. RESULTS: A total of 137 rheumatology HPs (95 female; 27-65 years of age) completed questionnaires. CFA showed that a four-factor model provided a marginally acceptable fit. Analysis of four focus groups (n = 24; 19 female; 30-60 years of age) identified five themes relating to HPs' perceptions of exercise and joint health in RA patients: 'Exercise is beneficial', 'Concerns about damage to joints', 'Patients have barriers to exercise', 'HP knowledge differs' and 'Patients may think service delivery is vague'. CONCLUSIONS: HPs were highly aware of the benefits and importance of exercise for RA patients. However, to remove the patient perception that HPs lack certainty and clarity regarding exercise it is important to ensure: (i) consistent promotion of exercise across the whole MDT; (ii) clear provision of information regarding rest, joint protection and exercise; (iii) HP education to ensure consistent, accurate knowledge, and understanding of the potential for conflicting advice when promoting exercise as part of an MDT. Copy © 2016 John Wiley & Sons, Ltd.
27894399 Effect of iguratimod and methotrexate on RANKL and OPG expression in serum and IL-1β-indu 2016 Oct 31 The receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK)/osteoprotegerin (OPG) system plays a key role in rheumatoid arthritis (RA)-associated bone erosion. The upregulation of the RANKL/OPG ratio promotes bone erosion. The objective of this study is to explore the effects of iguratimod, a small-molecule disease-modifying antirheumatic drug (DMARD), alone or in combination with methotrexate (MTX), on RANKL and OPG expression in RA. We performed an enzyme-linked immunosorbent assay (ELISA) to investigate the modulatory effects of iguratimod, MTX, or their combination on serum RANKL and OPG levels of patients with RA before and after treatment for 12 and 24 weeks. Furthermore, fibroblast-like synoviocytes (FLS) from patients with RA were interleukin (IL)-1β-stimulated and then treated with different concentrations of iguratimod, MTX, or both, and RANKL and OPG expressions were investigated by using ELISA, quantitative real-time polymerase chain reaction (qPCR) and western blot analysis. We found that RANKL levels and the RANKL/OPG ratio significantly decreased in both serum and IL-1β-induced RA FLS after treatment. Moreover, combination therapy with iguratimod and MTX showed an even stronger inhibition than each drug alone did. Our results suggest that iguratimod and MTX, especially in combination, efficaciously protected against bone erosion by suppressing the production of RANKL.
25037898 Traditional Chinese medication for rheumatoid arthritis: more than what meets the eye. 2015 Feb There is an increasing interest in the role of traditional Chinese medicine (TCM) in rheumatoid arthritis (RA), as evidenced by recent trials comparing their efficacy against established disease-modifying antirheumatic drugs. While the TCM in these trials seem to support a favorable cost-benefit ratio, many products are marketed under the guise of TCM, potentially exposing the user to unpredicted adverse events. We present the case of a patient with RA, who developed side effects from treatment with adulterated TCM. While TCM may be of value in the treatment of rheumatic diseases, their application in routine care continues to warrant careful consideration of safety and reliability.
25746854 QuantiFERON-TB Gold In-Tube assay for screening arthritis patients for latent tuberculosis 2015 BACKGROUND: Patients undergoing anti-tumor necrosis factor (TNF) treatment are at an increased risk of reactivating a latent tuberculosis infection (LTBI). This study evaluated the effectiveness of the QuantiFERON-TB Gold In-Tube (QFT) assay for diagnosing LTBI in arthritis patients undergoing anti-TNF treatment. METHODS: We enrolled 342 consecutive patients from August 2007 to October 2013: 176 (51.5%) patients with ankylosing spondylitis and 166 (48.5%) with rheumatoid arthritis. Screening tests included tuberculin skin test (TST) and QFT assay. Positive QFT results, regardless of TST results, were considered an indicator for LTBI treatment. RESULTS: Bacillus Calmette-Guérin scars were found in 236 (69.0%) patients. Of 342 patients, TST and QFT were positive in 122 (35.7%) and 103 (30.1%) patients, respectively, and discordant in 101 (29.5%) patients. During a median follow-up duration of 41.7 months, five patients (1.5%) developed TB in a median of 20.8 months after initiation of anti-TNF treatment (428/100,000 person-years). TB did not occur in 62 TST+/QFT+ patients who received LTBI treatment. Of 41 TST-/QFT+ patients who received LTBI treatment, one (2.4%) developed TB 20.5 months after starting anti-TNF treatment (705/100,000 person-years). Of 60 TST+/QFT- patients who did not receive LTBI treatment, two (3.3%) developed TB 20.8 and 22.0 months after starting anti-TNF treatment (871/100,000 person-years). Of 179 TST-/QFT- patients, two (1.1%) developed TB 7.2 and 22.7 months, respectively, after initiating anti-TNF treatment (341/100,000 person-years). TB incidence rate during the follow-up period did not differ among TST-/QFT+, TST+/QFT-, and TST-/QFT- patients (P = 0.661). CONCLUSION: QFT might be used instead of TST for diagnosing LTBI in patients before starting anti-TNF therapy in countries, such as Korea, where the TB prevalence is intermediate and the BCG vaccination is mandatory at birth. In the absence of a true gold standard test for LTBI, however, there is still a risk of TB development during anti-TNF treatment.
26213106 Impact of Total Knee Arthroplasty as Assessed Using Patient-Reported Pain and Health-Relat 2015 Sep OBJECTIVE: To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). METHODS: Patients with rheumatologist-diagnosed arthritis undergoing primary TKA during 1999-2012 were identified. Indices of pain (overall, index knee, and contralateral knee) and health-related quality of life (HRQOL) were obtained in 3 consecutive 6-month intervals: preoperative (baseline), perioperative, and postoperative (recovery). Descriptive statistics and one-way analysis of variance were used to compare TKA outcomes by diagnosis. Effect sizes and standardized response means (SRMs) were calculated between baseline and recovery. RESULTS: Of the participating 18,897 patients, 834 of those with RA (5.3%) and 315 of those with OA (10.2%) had undergone index TKA at similar mean ages (65 and 68 years). Post-TKA, significant improvements were observed for most domains of pain, function, and HRQOL within both disease groups, with greater impact in OA. Based on the SRM, the maximum improvement was shown in index knee pain (SRM -1.33 in RA and -1.34 in OA; effect size -1.75 and -1.94, respectively). The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive HRQOL indices in detecting post-TKA improvement in RA. A diagnosis of RA, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following TKA. CONCLUSION: TKA is highly effective in reducing clinically relevant knee pain (to a greater extent than its effect on other subjective HRQOL indices in patients with RA), although this improvement is less marked as compared to that among patients with OA. TKA serves as a "time machine" via which patients can return to a lifestyle with less disability, before the arthritis process catches up in RA.
26914724 Implementing Treat-to-Target Practices for Chronic Pain Through Shared Decision Making: Re 2017 Feb OBJECTIVE: Treat-to-target (T2T) includes a target or goal, standard symptom assessment, and a treatment decision. In specialties that threat chronic pain, T2T is expected to be implemented collaboratively. The ability of patients to participate fully has been questioned, but these concerns have not been demonstrated empirically. The current study examined how patient self-assessed symptom measures and illness beliefs affect their willingness to change their current treatment. METHODS: A total of 157 patients with rheumatoid arthritis completed a standard "disease activity" (DA) battery consisting of current joint pain, recent pain, daily functioning, and generality disability assessments, along with an illness belief questionnaire and a willingness to change measure. Data were collected at 2-month intervals over a 6-month period. Single and multiple influences on willingness to change were examined using linear mixed models. RESULTS: Willingness is strongly and directly associated with DA scores. Beliefs that were significant as single factors became nonsignificant once DA scores were introduced. The findings established a strong and consistent link between DA scores and willingness, and ruled out the prospect that illness beliefs mediate or moderate this relationship. It was also found that willingness to change is directly related to the number of significant self-reported symptoms. CONCLUSION: Concerns about the ability of patients to participate in a collaborative implementation of T2T were not substantiated. Future studies can examine the subtle interplay of goals, assessments, and treatment decisions and clarify outstanding issues about the practice of clinical decision making.
25990005 Predictors of response to TNF-α antagonist therapy in Chinese rheumatoid arthritis. 2015 Jul This study aimed to investigate the clinical, immunological, and radiologic predictors of response to tumor necrosis factor (TNF)-α antagonist therapy in Chinese rheumatoid arthritis (RA). Ninety RA patients were divided into two groups according to their responsiveness to TNF-α antagonist therapy at 1 month: group A (responders) and group B (non-responders). After 3 months of therapy, all the 90 patients were re-assessed and re-divided into another two groups: group C (responders) and group D (non-responders). Serum samples and clinical characteristics as well as radiographic features were collected at baseline, first month, and third month post-initial administration of TNF-α antagonist. Serum TNF-α, interleukin (IL)-6, IL-8, IL-34, and matrix metalloproteinase (MMP)-3 were measured by enzyme-linked immunosorbent assay (ELISA). Disease activity and Sharp score were evaluated. (1) Comparisons between groups A and B: subjects in group A showed a lower level of erythrocyte sedimentation rate (ESR) and a higher level of albumin (ALB) at baseline than that of group B (p < 0.05). The cutoff value of ALB for prediction was ≥34.9 g/l and that of ESR was ≤55.5 mm/h. (2) Comparisons between groups C and D: group C showed lower levels of ESR, health assessment questionnaire (HAQ), and IL-34 at baseline (p < 0.05). The threshold for prediction were as follows: ESR ≤60 mm/h, HAQ ≤1.3125, and IL-34 ≤194.12 pg/ml. (3) The serum cytokines were positively correlated with C-reactive protein (CRP) and disease activity index, while ALB was negatively correlated with CRP and disease activity. Baseline ALB ≥34.9 g/l or ESR ≤55.5 mm/h might predict a good response at 1-month treatment of TNF-α antagonist, while baseline ESR ≤60 mm/h, HAQ ≤1.3125, and IL-34 ≤194.12 pg/ml might predict a good response at 3-month treatment.
25352238 Salvia miltiorrhiza injection restores apoptosis of fibroblast-like synoviocytes cultured 2015 Feb Salvia miltiorrhiza injection (SMI) is a water‑soluble agent, derived from Salvia miltiorrhiza (SM), that is traditionally used to treat cardiovascular and cerebrovascular diseases. Furthermore it has been demonstrated to possess the ability to induce apoptosis of tumor cells. However, it remains unclear whether SMI can induce apoptosis of rheumatoid arthritis (RA) fibroblast‑like synoviocytes (FLS), which are hyperplastic in RA due to defective apoptosis. There is also evidence that allogenic serum may be associated with the induction of apoptosis. The aim of the present study was to investigate the involvement of serum during SMI‑induced apoptosis in RA FLS. The results demonstrated that SMI could induce apoptosis of RA FLS, cultured with fetal bovine serum (FBS), in a dose‑dependent manner. In addition, SMI decreased the expression of nuclear factor‑κB in RA FLS nuclear extracts and inhibited the secretion of tumor necrosis factor‑α. Fas ligand expression was not detected in RA FLS, in either the presence or absence of SMI. The pro‑apoptotic genes B‑cell lymphoma 2 (Bcl‑2) associated X protein (Bax) and Fas, were shown to be upregulated following SMI stimulation, whereas the expression levels of the anti‑apoptotic gene Bcl‑2, were downregulated. Upon replacement of FBS with normal human serum, the apoptotic rate and Bax mRNA expression levels following SMI stimulation, were unchanged. However, culturing RA FLS with patient' serum (RPS), restored the apoptotic rate and Bax mRNA expression levels following SMI stimulation. There may be numerous mechanisms by which SMI inhibits RA FLS proliferation. The present study demonstrated that SMI can restore apoptosis of RA FLS cultured with RPS. These results indicate that SMI may have a potential role in the treatment of synovial hyperplasia of RA.
26481695 Radiographic quantifications of joint space narrowing progression by computer-based approa 2016 OBJECTIVE: To investigate the validity of a computer-based method using temporal subtraction in carpal joints of patients with rheumatoid arthritis (RA), which can detect the difference in joint space between two images with the joint space difference index (JSDI). METHODS: The study consisted of 43 patients with RA (39 females and 4 males) who underwent radiography at baseline and at 1-year follow-up. The joint space narrowing (JSN) of carpal joints on bilateral hand radiographs was assessed by our computer-based method, using the Sharp/van der Heijde method as the standard of reference. We compared the JSDI of joints with JSN progression in the follow-up period with that of those without JSN progression. In addition, we examined whether there is a significant difference in JSDI in terms of laterality or topology of the joint. RESULTS: The JSDI of joints with JSN progression was significantly higher than that of those without JSN progression (Mann-Whitney U test, p < 0.001). There was no statistically significant difference in the JSDI between the left and right carpal joints, which was analysed for five different joints altogether and each joint separately (Mann-Whitney U test, p > 0.05). There was statistically significant difference in JSDI among different joints (Kruskal-Wallis test, p = 0.003). CONCLUSION: These results suggest that our computer-based method may be useful to recognize the JSN progression on radiographs of rheumatoid wrists. ADVANCES IN KNOWLEDGE: The computer-based temporal subtraction method can detect the JSN progression in the wrist, which is the single most commonly involved site in RA.
27085681 Clinical effects of tocilizumab on cytokines and immunological factors in patients with rh 2016 Jun Interleukin (IL)-6 is one of the crucial proinflammatory cytokines. The dysregulation of IL-6 plays a pivotal role in rheumatoid arthritis (RA) and is involved in several of the common clinical manifestations associated with active RA. Recent therapies targeting IL-6 and tumor necrosis factor (TNF) have resulted in clinical improvements in signs and symptoms, disability and quality of life in patients with early and long-standing RA. Because it has been demonstrated that cytokines and inflammatory/immunological factors appear to be important and sensitive mediators in RA patients treated with tocilizumab and with anti-TNF biologics, it is important to investigate whether tocilizumab administration has any effect(s) on the profiles of cytokines and inflammatory/immunological factors and whether these changes correlate with the clinical improvement in RA disease activity. In this review, we discuss the effects on cytokine regulation and the differentiation of immune cells, especially T cells, after tocilizumab therapy in patients with RA.
26846283 Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral 2016 Mar Methotrexate (MTX) is still considered the drug of choice in rheumatoid arthritis (RA) management. Comparing subcutaneous (MTX SC) and oral (MTX OR) routes of administration is important to optimize the everyday therapeutic strategy in the real-life setting. This review summarizes scientific evidence currently available on this topic. As shown by pharmacokinetic studies, at the same dose level, bioavailability of MTX SC is significantly higher and less variable than that of MTX OR. This difference is even more pronounced for medium-to-high dosages (i.e., >15 mg/week). With regard to clinical response (Disease Activity Score-28, American College of Rheumatology Criteria), randomized, double-blind studies and retrospective or longitudinal analyses in real-life settings showed that MTX SC is more effective than MTX OR. This is true both in MTX-naive patients with early RA, and in patients who switch from MTX OR to MTX SC due to previous treatment failure, lack of efficacy and/or adverse events. Finally, MTX SC has a better tolerability profile than MTX OR, with fewer gastroenterological side effects. Delaying the use of more expensive biological therapies by switching from MTX OR to MTX SC in non-responders might provide cost savings, with relevant implications in the management of patients with RA. FUNDING: Alfa Wassermann.