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ID PMID Title PublicationDate abstract
25205591 Heterozygote genotypes for PADI4_89 were protectively associated with susceptibility to tu 2015 Apr The aim of this study was to determine whether peptidyl arginine deiminase (PADI) genes could affect susceptibility to tuberculosis (TB), which can be a presumptive base to explain the increased incidence of TB in patients with rheumatoid arthritis (RA) in Korean. The study population consisted of 47 patients with active TB, 35 patients with nontuberculous mycobacterial disease, 50 RA patients, and 83 healthy controls who had received comprehensive medical testing. Genomic DNA was isolated from peripheral blood mononuclear cells using a standard protocol. All of the patients and healthy controls were genotyped for two nonsynonymous SNPs in PADI4, namely PADI4_89, PADI4_90, and one synonymous SNP in PADI4_104. There was the complete linkage between PADI4_89 and PADI4_90 SNPs. In the allele and haplotype analyses of PADI4_89 and PADI4_104, no significant associations are observed between disease groups and control groups. The frequencies of heterozygote (A/G) for PADI4_89 were significantly lower in patients with active TB than in controls [adjusted odd ratios (OR) = 0.35, p values = 0.020]. When the analysis was conducted by overdominant model, more significant associations are observed (adjusted OR = 0.34, p values = 0.005). We found that heterozygote genotypes for PADI4_89 were protectively associated with susceptibility to TB.
25891943 Downregulation of microRNA‑221 decreases migration and invasion in fibroblast‑like syn 2015 Aug MicroRNAs (miRNAs/miRs) are a group of non-coding RNAs that regulate the activity of target mRNAs and cellular processes, and which have been implicated in the pathogenesis of autoimmune diseases. miR-221 is one of the miRNAs that regulate cell proliferation, invasion and apoptosis in tumors. However, the role of miR-221 in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, the present study was undertaken to identify the role of miR-221 in RA. The expression of miR-221 in serum and synovial tissues of patients with RA and healthy controls was confirmed by reverse transcription quantitative polymerase chain reaction analysis. The effects of miR-221 on pro-inflammatory cytokines and a chemokine were assessed by ELISA. The effects of miR-221 on cell apoptosis, migration and invasion in fibroblast-like synoviocytes (FLS) were also assessed in vitro. The results showed that miR-221 expression in serum and synovial tissues of patients with RA was higher than that in healthy controls. Downregulation of miR-221 significantly suppressed the expression of pro-inflammatory cytokines and the chemokine, and inhibited FLS cell migration and invasion via inhibiting vascular endothelial growth factor, matrix metalloproteinase (MMP)-3 and MMP-9 expression. In addition, downregulation of miR-221 significantly induced cell apoptosis and decreased survivin and X-linked inhibitor of apoptosis protein expression. These findings indicated that downregulation of miR-221 inhibited the expression of pro-inflammatory cytokines and the chemokine, suppressed FLS cell migration and invasion, and induced cell apoptosis. Therefore, miR-221 is likely to be implicated in RA pathogenesis via these mechanisms, and may be a target for the treatment of RA.
26886847 Rheumatoid arthritis patients undergoing total hip and knee arthroplasty have better in-ho 2016 Mar OBJECTIVES: Rheumatoid arthritis (RA) is known to be associated with multiple comorbidities and, therefore, overall management is critical for those patients undergoing elective major orthopaedic surgeries, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to compare in-hospital outcomes of elective THA and TKA between patients with and without RA in the US during the last decade. We hypothesised that patients with RA would have similar perioperative outcomes after elective THA and TKA. METHODS: Clinical data were derived from the US Nationwide Inpatient Sample (NIS) between 2000 and 2009. Patients who underwent elective THA and TKA were identified. Data regarding patient- and healthcare system-related characteristics, comorbidities, in-hospital complications, and mortality were retrieved. In-hospital outcomes of the procedures were compared between patients with and without RA. RESULTS: Comparison between patients with and without RA showed that patients with RA had significantly lower overall in-hospital complication rates following THA and TKA, and lower in-hospital mortality rate following THA. Patients with RA undergoing THA and TKA had decreased risk of overall in-hospital complications compared to those without RA. CONCLUSIONS: Contrary to our hypothesis, perioperative outcomes of elective THA and TKA in patients with RA were better than those in patients without RA. These results may indicate that patient selection and pre- and perioperative management of patients with RA undergoing elective THA and TKA were well conducted in the US during the last decade.
25302816 Methotrexate-related lymphoproliferative disorder arising in the gingiva of a patient with 2015 Sep Methotrexate (MTX) is the primary drug used in the management of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. MTX is a strong immunosuppressive agent and has been reported to cause iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPDs). Stomatitis caused by MTX-related cytotoxicity may occur, but gingival MTX-related LPDs are rare. In this article we present a case of gingival MTX-related LPD in a 60-year-old male with RA. The local findings of the gingival ulceration and alveolar bone exposure were similar to those of bisphosphonate-related osteonecrosis of the jaw. However, he had never received bisphosphonate therapy. The biopsy specimen of the gingival lesion was diagnosed as diffuse large B-cell lymphoma with Epstein-Barr virus positivity. Immediate withdrawal of MTX resulted in marked remission of the LPD.
26766553 Rates, factors, reasons, and economic impact associated with switching in rheumatoid arthr 2016 Jun Objectives To identify how many RA patients newly-initiated on bDMARD therapy switch to another bDMARD during the first year of treatment; to evaluate the factors and reasons associated with bDMARD switching; and to compare the RA-related healthcare resource utilization (HCRU) and costs between switchers vs non-switchers during the post-index period. Methods A retrospective cohort study was conducted in RA patients using the Kaiser Permanente Southern California (KPSC) database with the study time period of January 1, 2007 to December 31, 2012. The index date was defined as the date of the first bDMARD prescription. Patients had to have continuous membership eligibility with drug benefit and no prior history of bDMARD during the 24 months prior to the index date. bDMARD switching was defined as a different bDMARD claim during post-index. A multivariable logistic regression model was used to evaluate factors associated with switchers vs non-switchers. Chart notes were reviewed to evaluate reasons for switching from index bDMARD. RA-related HCRU use and costs were evaluated using a generalized linear model (GLM) with gamma distribution and log link function. Results Two hundred and fifty-one patients (12%) switched from their index bDMARD to a different bDMARD during the post-index period. bDMARD switchers were more likely to be female, of Asian/Pacific race, younger than ≤65 years of age, overweight, CCI score ≤2, initiating etanercept or adalimumab, and have a commercial insurance plan compared to non-switchers. Reasons for switching were related mostly to lack or loss of efficacy (∼51%); bDMARD switchers had overall mean adjusted RA related total costs that were 25% higher (p = 0.04) compared to non-switchers. Conclusion It is important for RA patients to receive appropriate therapy and consider bDMARD with different mechanisms of action to decrease subsequent switching, and decrease overall RA related costs as shown in this study.
28535888 Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated pe 2017 May OBJECTIVE: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. METHODS: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. RESULTS: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. CONCLUSIONS: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.
25461298 The association between dry eye disease and depression and anxiety in a large population-b 2015 Mar PURPOSE: To investigate the association between dry eye disease and each of depression and anxiety. DESIGN: Retrospective, case-control study. METHODS: setting: University of North Carolina outpatient clinics. study population: All patients over the age of 18 years seen between July 2008 and June 2013 were included in the analysis. observation procedure: Cases were defined according to ICD-9 diagnosis codes for dry eye disease, anxiety, and depression. outcome measure: Separate odds ratios were calculated for dry eye disease and each of anxiety and depression. Similar odds ratios were also calculated between dry eye disease and rheumatoid arthritis, a systemic disease with a known association with dry eye, as a way of validating our approach. RESULTS: A total of 460 611 patients were screened; 7207 patients with dry eye were included, while 20 004 patients with anxiety and 30 100 patients with depression were included. The adjusted odds ratio for dry eye disease and anxiety was 2.8 (95% confidence interval [CI] 2.6-3.0). For dry eye disease and depression, the odds ratio was 2.9 (95% CI 2.7-3.1). CONCLUSIONS: We identified a statistically significant association between dry eye disease and each of depression and anxiety. Such an association has implications for ophthalmologists in the management and treatment of dry eye disease.
28104543 A review of human diseases caused or exacerbated by aberrant complement activation. 2017 Apr Complement is the backbone of our innate immune system. It is of ancient evolutionary origin, being traced back to horseshoe crabs 350 million years ago. It consists today of more than 25 proteins which must work together like clockwork to distinguish friend from foe. Self-attack by the complement system can occur whenever it fails to do so. This failure has been reported to occur in an estimated 22 human diseases. A significant number of these are chronic degenerative neurological disorders. In some, there is overwhelming evidence that complement self-attack causes the disease. In many others, it is considered only to contribute to the overall pathology. Finding effective therapeutic agents should be a high priority for medical research. To date, the monoclonal antibody eculizumab is the only approved agent. Molecules under development include other monoclonal antibodies directed at C5, C3, and properdin, various aptamers to C3, and small molecules that are orally available.
25715838 Dynamic contrast-enhanced imaging of the wrist in rheumatoid arthritis: dedicated low-fiel 2015 Aug OBJECTIVE: To compare the assessment of wrist synovitis severity, synovial volume and synovial perfusion parameters on a dedicated low-field (0.25-T) to that of a high-field (3-T) whole-body MR system in patients with rheumatoid arthritis (RA). METHODS: Twenty-one patients (mean age 50.0 ± 9.8 years) with active RA were recruited prospectively. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at both 0.25 T and 3 T. Three MRI-derived parameters, synovitis severity (RAMRIS grade), synovial volume (ml(3)) and synovial perfusion indices (maximum enhancement and enhancement slope), were compared. RESULTS: Comparing 0.25- and 3-T MRI, there was excellent agreement for semiquantitative assessment (r: 0.80, p < 0.00001) of synovitis (RAMRIS) as well as quantitative assessment (r: 0.94, p < 0.00001) of synovial volume. Good agreement for synovial Emax (r: 0.6, p = 0.002) and fair agreement (r: 0.5, p = 0.02) for synovial Eslope was found. CONCLUSIONS: Imaging of the RA wrist at 0.25 T yields excellent correlation with 3 T with regard to the synovitis activity score (RAMRIS) and synovial volume measurement. Fair to good correlation between low- (0.25-T) and high-field (3-T) MR systems was found for perfusion parameters, being better for Emax than for Eslope.
27065315 Modeling of the clinical and economic impact of a risk-sharing agreement supporting a trea 2016 Aug OBJECTIVES: To evaluate the cost-effectiveness of a Treat-to-Target strategy with certolizumab pegol in patients with rheumatoid arthritis in the context of a pay-for-performance agreement in which medication costs are refunded in case of discontinuation during the first 3 months of treatment. METHODS: The Treat-to-Target strategy consisted of a systematic switch to second-line tumor necrosis factor (TNF)α inhibitor in case of an unmet ACR50 response at 3 months compared to current routine clinical practice. A reference cohort treated first-line with certolizumab pegol according to current practice without systematic switching was considered as the comparator. A decision-tree model was constructed to estimate clinical outcome (health assessment questionnaire-disability index or HAQ-DI score), time spent in ACR50 response (ACR 50), and direct costs of treatment over a 2-year period. HAQ scores were derived from American College of Rheumatology 50 (ACR50) responses. All TNFα inhibitors were assumed to have equivalent efficacy and tolerability. Costs were estimated at 2013 French retail prices (date of the pay-for-performance agreement). RESULTS: The mean duration of an ACR50 response was 1.23 years in the Treat-to-Target strategy certolizumab pegol cohort vs 0.98 years in the reference cohort, resulting in a mean gain in HAQ at 24 months of 0.117. The Treat-to-Target strategy with a mix of TNFα inhibitors as second-line therapy was more expensive than the reference strategy in absolute terms, but this difference was entirely offset by the pay-for-performance agreement. The Treat-to-Target strategy was, thus, cost-neutral over a 2-year period after the payback of CZP cost for patients not achieving the target at 3 months. CONCLUSIONS: In the context of a pay-for-performance agreement, the management of patients with rheumatoid arthritis using a Treat-to-Target strategy with certolizumab pegol in first line is dominant compared to standard use of this drug in the French setting in 2013.
29786291 [CLINICAL OBSERVATION OF ROTATING-PLATFORM PROSTHESIS FOR VALGUS KNEE DEFORMITY]. 2016 May 8 OBJECTIVE: To investigate the effectiveness of rotating-platform prosthesis for valgus knee deformity in total knee arthroplasty (TKA). METHODS: A retrospective analysis was made on the clinical date of 25 cases (28 knees) of valgus deformity undergoing primary TKA by using Gemini MK II rotating-platform prosthesis. There were 6 males (7 knees) and 19 females (21 knees), aged from 47 to 82 years, with an average age of 64.8 years. The unilateral knee was involved in 22 cases and the bilateral knees in 3 cases. The causes included osteoarthritis in 20 cases (22 knees), rheumatoid arthritis in 4 cases (5 knees), and traumatic arthritis in 1 case (1 knee). The disease duration was 2-22 years (mean, 10.4 years). The main clinical symptoms were arthralgia combined with limited movement. According to the Keblish grade, there were 13 knees of mild deformity, 11 knees of moderate deformity, and 4 knees of severe deformity. RESULTS: All incisions healed by first intension. No complications of infection, cutaneous necrosis, deep venous thrombosis, and pulmonary embolism occurred. The postoperative follow-up duration was 12-60 months (mean, 25.4 months). Medial instability and palsies of nervus peroneus communis occurred in 1 and 2 cases respectively, and all were cured after symptomatic treatment. No patellar and polysthylene insert dislocation, prosthetic loosening or infection was observed. The Hospital for Special Surgery (HSS) score, femoral tibial angle, maximun flexion and extension angles, knee range of motion, and patellar score were significantly improved at last follow-up when compared with preoperative ones (P<0.01). CONCLUSIONS: The rotating-platform prosthesis for valgus deformity can obtain satisfactory effectiveness, but it requires precise soft tissue balancing technology, and the long-term effectiveness remains further observation.
25933137 Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered 2015 BACKGROUND: Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA). METHODS: We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis. RESULTS: Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs. CONCLUSIONS: The levels, composition, and MW distribution of all currently known lubricants in SF--HA, lubricin, PLs--vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction.
25318612 Treatment of rheumatoid arthritis with methotrexate alone and in combination with other co 2015 Feb The aim of this study was to evaluate the effect of treatment with methotrexate (MTX), by itself or combined with other non-biological disease-modifying antirheumatic drugs (DMARDs) (methotrexate, MTX with prednisolone, MTX with leflunomide, MTX with chloroquine, and MTX with sulfasalazine) on clinimetric outcomes in a retrospective cohort with a 6-month follow-up and under a Treat to Target (T2T) approach. Patients in treatment with conventional DMARDs and classified as moderate disease activity (MDA) and high disease activity (HDA) were included. Changes in disease activity score (DAS28), health assessment questionnaire (HAQ), tender joint count (TJC), and swollen joint count (SJC) are compared using the Wilcoxon nonparametric test for paired data. Hypothesis contrasts were raised in order to look for differences between the different exposure groups and the outcomes defined by means of the Kruskal-Wallis (KW) nonparametric test. Follow-up was documented in 307 patients, including 250 (81.4%) women. At the onset, 243 subjects (79.2%) were classified as MDA and 64 (20.9%) in HDA. A total of 247 subjects (80.4%) presented some degree of improvement, with 156 subjects (51%) entering remission, which is a significant number (p value = 0.047). There were no differences in the level of severity between the treatment groups (p = 0.98). This study, developed in a cohort of patients with RA with moderate or severe disease activity who were treated with MTX by itself or combined with other non-biological DMARDs under T2T strategy, showed a decrease in the severity of disease activity in 80% of patients. The difference between monotherapy (MTX) and the combinations with other non-biological DMARDs could not be established.
26538398 Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arth 2015 Dec 1 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance.
26886687 Parvovirus infection in early arthritis. 2016 Mar OBJECTIVES: To analyse the subgroup of early arthritis patients with new onset parvovirus infections for details that may help narrow the population tested. METHODS: From their routine patient charts, patient histories and clinical and serological data were obtained for all 130 patients of the Rheumatology division with parvovirus serology performed. 11 patients had acute parvovirus infections, defined by specific IgM antibodies. 95 patients had a previous infection, 16 were never infected, together forming the n=111 control group, and 8 patients had to be excluded. RESULTS: Most patients with acute parvovirus infection had an acute onset, highly symmetrical polyarthritis of small joints, which was preceded by prodromal symptoms. Positive ANA were frequently found, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were only mildly elevated. No frank synovitis was found longer than two weeks after disease onset. Most patients were free of symptoms within three months, and no patient in the parvovirus group developed rheumatoid arthritis or a connective tissue disease. CONCLUSIONS: Parvovirus serology may be helpful in patients with acute polyarthritis of very recent onset, and if they give a history of prodromal symptoms, in particular. In most instances, parvovirus arthritis is an acute disease, which is rapidly self-limiting.
24442879 Significant associations of antidrug antibody levels with serum drug trough levels and the 2015 Mar OBJECTIVE: To evaluate the associations between (1) antidrug antibody (ADAb) and therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate the correlation between two different ELISA methods for detecting drug levels, and (2) to determine the optimal cut-off drug levels for good European League Against Rheumatism (EULAR) response. METHODS: ADAb levels were determined by bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were determined by receiver-operating characteristic curve analysis. RESULTS: ADAb was detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12-month therapy using bridging ELISA and radioimmunoassay respectively, but not detected in any of etanercept-treated patients. The presence of ADAb was associated with lower EULAR response and lower drug levels compared with those without ADAb (both p<0.001). Drug trough levels were positively associated with DAS28 decrement (ΔDAS28) (all p<0.001). The optimal cut-off trough levels for adalimumab were 1.274 μg/mL and 1.046 μg/mL, and those for etanercept were 1.242 μg/mL and 0.800 μg/mL for good EULAR response assessed at the 6th and 12th month, respectively. CONCLUSIONS: ADAb levels were inversely correlated with therapeutic response and drug levels. The positive correlation between drug levels and ΔDAS28 indicates that drug monitoring would be useful to evaluate therapeutic response of TNF-α inhibitors.
27283332 Tapering conventional synthetic DMARDs in patients with early arthritis in sustained remis 2016 Dec OBJECTIVES: With early and intensive treatment many patients with early RA attain remission. Aims were to investigate (1) the frequency and time to sustained remission and subsequent tapering in patients initially treated with conventional synthetic disease modifying anti-rheumatic drug ((cs)DMARD) strategies and (2) the frequency and time to flare and regained remission in patients tapering csDMARDs and biological (b)DMARDs during 2 years of follow-up. METHODS: Two-year follow-up data from the treatment in the Rotterdam Early Arthritis Cohort (tREACH) cohort were used. Patients were randomised to initial treatment with triple DMARD therapy (iTDT) with glucocorticoid (GC) bridging or methotrexate monotherapy (iMM) with GC bridging. Patients were evaluated every 3 months. In case Disease Activity Score (DAS) was >2.4 treatment was switched to a TNF-blocker. In case DAS<1.6 at 2 consecutive time points, tapering was initiated according to protocol. Outcomes were rates of sustained remission (DAS<1.6 at 2 consecutive time points), flare (medication increase after tapering) and remission after flare (DAS<1.6). Data were analysed using Kaplan-Meier analyses. RESULTS: During 2 years of follow-up, sustained remission was achieved at least once by 159 (57%) of patients, of whom 118 and 23 patients initiated tapering of csDMARDs and bDMARDs, respectively. Thirty-four patients achieved drug-free remission. Flare rates were 41% and 37% and within 1 year, respectively. After flare, 65% of patients tapering csDMARDs re-achieved remission within 6 months after treatment intensification. CONCLUSIONS: Regardless of initial treatment strategy, 57% of patients achieved sustained remission during 2 years of follow-up. Flare rates were 41% and 37% within 12 months in patients tapering csDMARDs and bDMARDs, respectively. TRIAL REGISTRATION NUMBER: ISRCTN26791028; Post-results.
27549792 Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthrit 2016 Nov The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10-20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. TRIAL REGISTRATION NUMBER: DRKS00004940.
27385284 Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXC 2016 Jul 7 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA.
27253519 Progress in understanding the safety and efficacy of Janus kinase inhibitors for treatment 2016 Oct INTRODUCTION: Treatment of rheumatoid arthritis (RA) has improved considerably following the advent of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, these drugs require special storage and transportation. Janus kinase (JAK) inhibitors are oral synthetic DMARDs that inhibit the non-receptor tyrosine kinase family Janus kinase. Recently, many JAK inhibitors are being developed as new therapies for patients with RA. AREAS COVERED: In this article, we mainly review the efficacy and safety of JAK inhibitors currently under investigation. Tofacitinib has already been approved in 43 countries except in the EU. Results of three JAK inhibitors (baricitinib, decernotinib, and peficitinib) in phase III are consistent with that of tofacitinib. Tofacitinib and baricitinib were partially effective in patients who had an inadequate response to biological DMARDs. Expert commentary: JAK kinase inhibitors provide a new therapeutic approach for rheumatoid arthritis. Meanwhile, further studies are needed to determine their risk-benefit ratio and the most appropriate patients suitable for such therapy.