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ID PMID Title PublicationDate abstract
27659808 Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteopo 2017 Jul OBJECTIVES: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis. METHODS: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n = 49) or traditional bisphosphonates (n = 49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment. RESULTS: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate. CONCLUSIONS: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.
25617259 Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis. 2015 May A 47-year-old woman with rheumatoid arthritis (RA) treated successively with infliximab, abatacept, and etanercept spontaneously developed subcutaneous bruises and a noncompressive hematoma 11 months after starting etanercept therapy (50mg/week). Her prothrombin time was normal but her activated partial thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a circulating anticoagulant (Rosner index, 45; normal,<13) due to an anti-factor VIII antibody in a titer of 45 Bethesda units. Her factor VIII level was less than 1% (normal range, 55-150). The etanercept and leflunomide were stopped and prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab, two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti-factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A remission was achieved 9 months after the diagnosis of acquired hemophilia and was sustained at last follow-up after 3 years. This new case of acquired hemophilia in a patient with RA may reflect a simple association or an inducing role of etanercept.
26290149 Associations of human leukocyte antigens with autoimmune diseases: challenges in identifyi 2015 Nov The mechanism of genetic associations between human leukocyte antigen (HLA) and susceptibility to autoimmune disorders has remained elusive for most of the diseases, including rheumatoid arthritis (RA) and type 1 diabetes (T1D), for which both the genetic associations and pathogenic mechanisms have been extensively analyzed. In this review, we summarize what are currently known about the mechanisms of HLA associations with RA and T1D, and elucidate the potential mechanistic basis of the HLA-autoimmunity associations. In RA, the established association between the shared epitope (SE) and RA risk has been explained, at least in part, by the involvement of SE in the presentation of citrullinated peptides, as confirmed by the structural analysis of DR4-citrullinated peptide complex. Self-peptide(s) that might explain the predispositions of variants at 11β and 13β in DRB1 to RA risk have not currently been identified. Regarding the mechanism of T1D, pancreatic self-peptides that are presented weakly on the susceptible HLA allele products are recognized by self-reactive T cells. Other studies have revealed that DQ proteins encoded by the T1D susceptible DQ haplotypes are intrinsically unstable. These findings indicate that the T1D susceptible DQ haplotypes might confer risk for T1D by facilitating the formation of unstable HLA-self-peptide complex. The studies of RA and T1D reveal the two distinct mechanistic basis that might operate in the HLA-autoimmunity associations. Combination of these mechanisms, together with other functional variations among the DR and DQ alleles, may generate the complex patterns of DR-DQ haplotype associations with autoimmunity.
26556048 Twelve-Year Retention Rate of First-Line Tumor Necrosis Factor Inhibitors in Rheumatoid Ar 2016 Apr OBJECTIVE: To evaluate the 12-year survival of the first tumor necrosis factor inhibitor (TNFi) treatment in a cohort of rheumatoid arthritis (RA) patients, comparing the between-groups discontinuation rates for infliximab, etanercept, and adalimumab. METHODS: RA patients treated with their first TNFi were investigated from a local registry. Before and after adjusting for propensity scores, overall and by individual TNFi 12-year drug retention was evaluated. Drug survival rates were calculated using the Kaplan-Meier method and compared by the Cox extended model. Subanalyses were performed according to concomitant methotrexate (MTX) and discontinuation reasons. RESULTS: Of 583 patients, 222 were treated with infliximab, 179 with etanercept, and 182 with adalimumab; 33.7% and 26% discontinued the first TNFi because of inefficacy or adverse events, respectively. The overall 12-year drug survival rate for the unmatched population was 23.4%. In the propensity score-adjusted population, the hazard ratio (HR) for treatment discontinuation was significantly greater for adalimumab and infliximab versus etanercept (HR 2.89 [95% confidence interval (95% CI) 2.2-3.78] and HR 2.56 [95% CI 1.92-3.4], respectively), and no difference was found between and for adalimumab versus infliximab (HR 1.16 [95% CI 0.91-1.47]). The incidence of withdrawal due to secondary inefficacy was stable from 3 to 12 years for etanercept, but progressively increased for the monoclonal antibodies. Concomitant MTX significantly increased the survival of both adalimumab and etanercept (HR 1.48 [95% CI 1.18-1.86]). CONCLUSION: The overall 12-year drug survival rate was 23.4%, being significantly higher for etanercept than adalimumab and infliximab. Etanercept discontinuations for inefficacy did not increase from 3 to 12 years. Concomitant MTX increased adalimumab and etanercept drug survival.
27634311 What are the dangers of biological therapy discontinuation or dose reduction strategies wh 2016 Nov Treatment with biological DMARDs (bDMARDs) has meant that remission or low disease activity (LDA) is now a realistic goal for patients with rheumatoid arthritis (RA). However, as in the case of all long-term therapies, potential side-effects give rise to concern. The main reasons for withdrawing or tapering bDMARDs are safety and the sustainability of national healthcare systems. Given these data our review has been focused on important question: whether conventional, including steroids, or bDMARDs can be reduced or even stopped in patients with stable established RA or early RA. Areas covered: The studies included in the evaluation had to be RCTs, observational studies, systematic reviews evaluating the withdrawing or tapering bDMARDs in RA patients who have been on long-term treatment and have achieved remission or LDA. A search was made in the MEDLINE and EMBASE databases from 1980 to May 2016. Expert commentary: There is curently no standardised way of identifying the patients for whom reducing bDMARD therapy is appropriate. Clinical experience and data from de-escalation studies suggest that patients with RA in sustained remission are the best target population for studying drug-tapering regimens, and that LDA should not be considered an adequate indication for bDMARD de-escalation because it could hide a persistent amount of inflammation.
26163921 Revision Proximal Interphalangeal Arthroplasty: An Outcome Analysis of 75 Consecutive Case 2015 Oct PURPOSE: To examine the outcomes and complications associated with revision proximal interphalangeal (PIP) joint arthroplasty. METHODS: An analysis of 75 consecutive revision PIP joint arthroplasties in 49 patients, performed between 1998 to 2012, was performed. The mean age at the time of surgery was 58 years. Thirty-two patients had a history of prior PIP joint trauma, and 18 patients had rheumatoid arthritis. There were 12 constrained (silicone) implants and 63 nonconstrained implants (34 pyrocarbon and 29 metal-plastic). RESULTS: Over the 14-year period, 19 (25%) fingers underwent a second revision surgery. Second revision surgeries were performed for infection, instability, flexion contracture, and heterotopic ossification. The 2-, 5-, and 10-year survival rates were 80%, 70%, and 70%, respectively, for patients requiring a second revision for PIP joint arthroplasty. Worse outcomes were seen with postoperative dislocations, pyrocarbon implants, and when bone grafting was required. Two operations were complicated by intraoperative fractures, but neither required stabilization. Sixteen patients undergoing revision surgery experienced a postoperative complication, including 2 infections, 1 postoperative fracture, 3 cases of heterotopic ossification, and 10 PIP joint dislocations. The volar approach and the use of a pyrocarbon implant was associated with increased rates of heterotopic ossification, whereas preoperative instability increased the rates of PIP joint dislocation following revision. At a mean of 5.3 years (range, 2-10 years) follow-up, 98% of patients had good pain relief but decreased PIP joint total arc of motion. CONCLUSIONS: Proximal interphalangeal joint arthroplasty in the revision setting represents a challenge for surgeons. Revision arthroplasty was associated with a 70% 5-year survival but with a high incidence of complications. Instability was associated with worse outcomes. In this series, silicone and metal-polyethylene implants had lower rates of implant failure and postoperative complications than ones made from pyrocarbon.
27203435 Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish P 2016 INTRODUCTION: The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort. METHODS: Periodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry (DHR), where dental diagnostic- and treatment codes on the adult Swedish population have been registered. Dental records from 100 cases and controls were reviewed to validate the periodontal diagnostic codes in DHR. RESULTS: The reviewed dental records confirmed 90% of the periodontitis diagnoses in DHR among RA cases, and 88% among controls. We found the positive predictive value of periodontitis diagnoses in the DHR to be 89% (95% CI 78 to 95%) with a sensitivity of 77% (95% CI: 65 to 86%). In total, 86% of EIRA participants were identified in DHR. The risk for periodontitis increased by age and current smoking status in both cases as well as controls. No significant differences in prevalence of periodontal disease in terms of gingivitis, periodontitis, peri-implantitis or increased risk for periodontitis or peri-implantitis were observed between RA cases and controls. In addition, there was no difference on the basis of seropositivity, ACPA or rheumatoid factor (RF), among patients with RA. CONCLUSIONS: Our data verify that smoking and ageing are risk factors for periodontitis, both in RA and controls. We found no evidence of an increased prevalence of periodontitis in patients with established RA compared to healthy controls, and no differences based on ACPA or RF status among RA subjects.
26648303 [An increased level of interleukin 27 in peripheral blood mononuclear cells and fibroblast 2015 Dec OBJECTIVE: To detect the levels of interleukin 27 (IL-27) and its receptor in peripheral blood mononuclear cells (PBMCs) and fibroblasts like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: PBMCs were collected from 20 patients with RA, 20 patients with OA and 20 healthy controls. FLS were cultured from synovial tissues of 4 patients with RA and 4 patients with OA. The levels of IL-27 mRNA in PBMCs and FLS were measured using real-time quantitative PCR. The expression of IL-27Rα in FLS was detected using immunocytochemical method. RESULTS: The level of IL-27 mRNA in PBMCs of patients with RA or OA was 1.81 or 2.07 times of the level in the normal subjects, respectively. There was no significant difference in the IL-27 mRNA level between RA and OA. However, IL-27 mRNA level in FLS of the patients with RA was 3.74 times of the level in the patients with OA. IL-27Rα expression in FLS of RA group was higher than that in OA group. CONCLUSION: The level of IL-27 in patients with RA and OA increased, and the level of IL-27 in FLS was higher than that in PBMCs in RA patients.
27038608 A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with r 2016 Apr 2 BACKGROUND: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA). METHODS: In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed. RESULTS: Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP. CONCLUSIONS: CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01217086 . Registered 4 Oct 2010.
26092218 Detection and measurement of rheumatoid bone and joint lesions of fingers by tomosynthesis 2016 Jan Rheumatoid arthritis (RA) is a systemic disease that is caused by autoimmunity. RA causes synovial proliferation, which may result in bone erosion and joint space narrowing in the affected joint. Tomosynthesis is a promising modality which may detect early bone lesions such as small bone erosion and slight joint space narrowing. Nevertheless, so far, the optimal reconstruction filter for detection of early bone lesions of fingers on tomosynthesis has not yet been known. Our purpose in this study was to determine an optimal reconstruction filter setting by using a bone phantom. We obtained images of a cylindrical phantom with holes simulating bone erosions (diameters of 0.6, 0.8, 1.0, 1.2, and 1.4 mm) and joint spaces by aligning two phantoms (space widths from 0.5 to 5.0 mm with 0.5 mm intervals), examining six reconstruction filters by using tomosynthesis. We carried out an accuracy test of the bone erosion size and joint space width, done by one radiological technologist, and a test to assess the visibility of bone erosion, done by five radiological technologists. No statistically significant difference was observed in the measured bone erosion size and joint space width among all of the reconstruction filters. In the visibility assessment test, reconstruction filters of Thickness+- and Thickness-- were among the best statistically in all characteristics except the signal-to-noise ratio. The Thickness+- and Thickness-- reconstruction filter may be optimal for evaluation of RA bone lesions of small joints in tomosynthesis.
25550337 Maintenance of remission following 2 years of standard treatment then dose reduction with 2015 Mar OBJECTIVES: To evaluate maintenance of response while reducing intravenous abatacept dose from ~10 mg/kg to ~5 mg/kg in patients with early rheumatoid arthritis (RA) who achieved disease activity score (DAS)28 (erythrocyte sedimentation rate, ESR) <2.6. METHODS: This 1-year, multinational, randomised, double-blind substudy evaluated the efficacy and safety of ~10 mg/kg and ~5 mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS28 (ESR) <2.6 at year 2 of the AGREE study. The primary outcome was time to disease relapse (defined as additional disease-modifying antirheumatic drugs, ≥2 courses high-dose steroids, return to open-label abatacept ~10 mg/kg, or DAS28 (C reactive protein) ≥3.2 at two consecutive visits). RESULTS: 108 patients were randomised (~10 mg/kg, n=58; ~5 mg/kg, n=50). Three and five patients, respectively, discontinued, and four per group returned to open-label abatacept. Relapse over time and the proportion of patients relapsing were similar in both groups (31% (~10 mg/kg) vs 34% (~5 mg/kg); HR: 0.87 (95% CI 0.45 to 1.69)). Mean steady-state trough serum concentration for the ~10 mg/kg group was 20.3-24.1 µg/mL, compared with 8.8-12.0 µg/mL for the ~5 mg/kg group. CONCLUSIONS: This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS28 (ESR) <2.6 after ≥1 year on abatacept (~10 mg/kg). TRIAL REGISTRATION NUMBER: NCT00989235.
26657009 Contribution of Peptide Backbone to Anti-Citrullinated Peptide Antibody Reactivity. 2015 Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1-2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs), which have been found in up to 70% of RA patients' sera, have received much attention. Several citrullinated proteins are associated with RA, suggesting that ACPAs may react with different sequence patterns, separating them from traditional antibodies, whose reactivity usually is specific towards a single target. As ACPAs have been suggested to be involved in the development of RA, knowledge about these antibodies may be crucial. In this study, we examined the influence of peptide backbone for ACPA reactivity in immunoassays. The antibodies were found to be reactive with a central Cit-Gly motif being essential for ACPA reactivity and to be cross-reactive between the selected citrullinated peptides. The remaining amino acids within the citrullinated peptides were found to be of less importance for antibody reactivity. Moreover, these findings indicated that the Cit-Gly motif in combination with peptide backbone is essential for antibody reactivity. Based on these findings it was speculated that any amino acid sequence, which brings the peptide into a properly folded structure for antibody recognition is sufficient for antibody reactivity. These findings are in accordance with the current hypothesis that structural homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g., why some Cit-Gly-containing sequences are not targeted by ACPAs.
25918734 Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function i 2015 Mesenchymal stem cells (MSCs) possess multipotent and immunomodulatory properties and are suggested to be involved in the pathogenesis of immune-related diseases. This study explored the function of bone marrow MSCs from rheumatoid arthritis (RA) patients, focusing on immunomodulatory effects. RA MSCs showed decreased proliferative activity and aberrant migration capacity. No significant differences were observed in cytokine profiles between RA and control MSCs. The effects of RA MSCs on proliferation of peripheral blood mononuclear cells (PBMCs) and distribution of specific CD4(+) T cell subtypes (Th17, Treg, and Tfh cells) were investigated. RA MSCs appeared to be indistinguishable from controls in suppressing PBMC proliferation, decreasing the proportion of Tfh cells, and inducing the polarization of Treg cells. However, the capacity to inhibit Th17 cell polarization was impaired in RA MSCs, which was related to the low expression of CCL2 in RA MSCs after coculture with CD4(+) T cells. These findings indicated that RA MSCs display defects in several important biological activities, especially the capacity to inhibit Th17 cell polarization. These functionally impaired MSCs may contribute to the development of RA disease.
26749303 Brief Report: Proatherogenic Cytokine Microenvironment in the Aortic Adventitia of Patient 2016 Jun OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of developing cardiovascular disease (CVD) via mechanisms that have not yet been defined. Inflammatory pathways, in particular within the vascular adventitia, are implicated in the pathogenesis of primary CVD but could be amplified in RA at the local tissue level. The aim of this study was to examine the aortic adventitia of coronary artery disease (CAD) patients with or without RA to determine the cytokine profile contained therein. METHODS: Aortic adventitia and internal thoracic artery biopsy specimens obtained from 19 RA patients and 20 non-RA patients undergoing coronary artery bypass graft surgery were examined by immunohistochemistry. RESULTS: Interleukin-18 (IL-18), IL-33, and tumor necrosis factor (TNF) were expressed in aortic adventitia biopsy specimens from both groups, and expression of these cytokines was significantly higher in RA patients. In RA patients, IL-33 expression in endothelial cells correlated positively with the number of swollen joints, suggesting a link between the systemic disease state and the local vascular tissue microlesion. CONCLUSION: The presence of the proinflammatory cytokines IL-18, IL-33, and TNF may play a role in the inflammatory process within the adventitia that contributes to plaque formation and destabilization. In theory, the amplified expression of these cytokines may contribute to the known increased occurrence and severity of CAD in patients with RA.
26449390 Outcome of Joint-Preserving Arthroplasty for Rheumatoid Forefoot Deformities. 2016 Mar BACKGROUND: Along with the recent advances in the pharmacological management of rheumatoid arthritis, there is a trend toward the use of joint-preserving surgery in the treatment of rheumatoid forefoot deformities. However, the clinical outcomes of joint-preserving surgery for rheumatoid forefoot deformities have not been assessed in comparison to resection arthroplasty. METHODS: We retrospectively evaluated 23 feet in 17 patients with rheumatoid forefoot deformities who underwent surgery between January 2010 and December 2013. The patients included 1 male (1 foot) and 16 females (22 feet), with a mean age of 62 years. The mean length of follow-up was 28 months. The patients were treated by 3 surgeons. One surgeon performed joint-preserving procedures (JP group) to the feet in which (1) no pain with motion existed, and (2) the range of motion in the first metatarsophalangeal (MTP) joint was greater than 30 degrees (n = 10); otherwise, resection arthroplasty with arthrodesis of the first MTP joint was performed (n = 3). The other surgeons performed resection arthroplasty in all cases (n = 10) (RA group, n = 13 in total). The clinical outcomes of the patients were evaluated using the Japanese Society for Surgery of the Foot (JSSF) hallux and lesser toe scales. RESULTS: There were no significant differences in the preoperative total JSSF scores for either the hallux (54.5 and 61.4 points) or the lesser toe (45.2 and 57.4 points) between the RA and JP groups, respectively. Postoperatively, the total JSSF scores for both the hallux (79.4 and 88.2 points) and lesser toes (73.6 and 87.7 points) showed significant improvement in both the RA and JP groups, respectively; however, the JP group showed a greater postoperative improvement. The scores relating to the function category on the hallux scale and the alignment category on the lesser toe scale were significantly higher in the JP group. CONCLUSION: With regard to the function of the hallux and the alignment of the lesser toes, the joint-preserving procedures for rheumatoid forefoot deformities resulted in better clinical outcomes than resection arthroplasty. LEVEL OF EVIDENCE: Level III, comparative case series.
26867708 Patient-specific risk factors for infection in arthroplasty procedure. 2016 Feb All patients are not equally at risk when it comes to postoperative infections, whether the risks are related to the environment or the patient. Patient-specific infection risk factors for arthroplasty should be a focal point during the preoperative consultation as they impact the treatment decision. Eighty percent of patients have at least one modifiable infection risk factor. These risk factors must be corrected preoperatively whenever possible so that the patient is operated under the best possible conditions, with the lowest possible infection risk. The screenings and preoperative preparations are multidisciplinary but must also involve the patient. The information provided to the patient must match the patient's infectious risk profile. This lecture will review every infection risk factor, whether it is modifiable or not, and then suggest how the treatment decision should be adapted to each patient's infection risk.
27744396 Quantification of Bone Marrow Edema by Magnetic Resonance Imaging Only Marginally Reflects 2016 Dec OBJECTIVE: Neck pain is common in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We investigated the correlation of bone marrow edema (BME) on magnetic resonance imaging (MRI) in RA and AS and its association with clinical complaints of neck pain. METHODS: Cervical spine short-tau inversion recovery-MRI and T1w-MRI of 34 patients with RA and 6 patients with AS complaining about neck pain were obtained. Clinical and laboratory data were available. BME was scored by 2 blinded readers using a modification of a published score, including various cervical sites. Degenerative changes were also quantified. RESULTS: Patients were predominantly women (82.5%), and mean ± SD age was 57.5 ± 11.8 years, C-reactive protein (CRP) was 0.8 ± 1.3 mg/dl, and pain score was 46.0 ± 17.5. BME was detected in 24/40 patients (60%) involving the atlantoaxial region (21%), vertebral bodies (75%), facet joints (29%), and spinous processes (46%). Degenerative changes were identified in 21/40 patients (52.5%), 13 (62%) of whom also had BME in vertebral bodies. No differences were found between patients with versus without cervical BME for clinical assessments: numeric rating scale pain (median ± interquartile range) 5.5 ± 3.0 vs 6.0 ± 4.0 (p = 0.69), Funktionsfragebogen Hannover 68.2 ± 41.0 vs 42.0 ± 55.5 (p = 0.19), Northwick pain score 44.4 ± 21.8 vs 47.2 ± 27.0 (p = 0.83), or CRP 0.40 ± 0.80 vs 0.60 ± 0.66 (p = 0.94). For patients with degenerative changes, symptom duration was longer than for patients without (10 ± 12.5 vs 5.0 ± 18.0 yrs, p = 0.73). CONCLUSION: In this small study of patients with RA and AS complaining about neck pain, BME was found in many different cervical sites, including the facet joints and the spinous processes. However, the occurrence and severity of BME did not correlate with the severity of neck pain.
25907700 The IL-23-IL-17 axis in inflammatory arthritis. 2015 Jul The discovery that the IL-23-IL-17 immune pathway is involved in many models of autoimmune disease has changed the concept of the role of T-helper cell subsets in the development of autoimmunity. In addition to TH17 cells, IL-17 is also produced by other T cell subsets and innate immune cells; which of these IL-17-producing cells have a role in tissue inflammation, and the timing, location and nature of their role(s), is incompletely understood. The current view is that innate and adaptive immune cells expressing the IL-23 receptor become pathogenic after exposure to IL-23, but further investigation into the role of IL-23 and IL-17 at different stages in the development and progression of chronic (destructive) inflammatory diseases is needed. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the two most common forms of chronic immune-mediated inflammatory arthritis, and the IL-23-IL-17 axis is thought to have a critical role in both. This Review discusses the basic mechanisms of these cytokines in RA and SpA on the basis of findings from disease-specific animal models as well as human ex vivo studies. Promising therapeutic applications to modulate this immune pathway are in development or have already been approved. Blockade of IL-17 and/or TH17-cell activity in combination with anti-TNF therapy might be a successful approach to achieving stable remission or even prevention of chronic immune-mediated inflammatory diseases.
26941130 Glucocorticoid-sparing in patients suffering from rheumatoid arthritis and treated with to 2016 Mar OBJECTIVES: To describe steroid-sparing in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: To evaluate the proportion of RA patients treated with more than 5 mg of prednisone (or equivalent)/day and starting TCZ who can receive less than 5 mg/day after 12 months without intensification of disease-modifying anti-rheumatic drugs (DMARDs), we conducted a non-interventional, multicentre, prospective study from 2011 to 2013. We included patients with moderate-to-severe RA, >18 years old, starting TCZ and receiving corticosteroids (GCs) at a dose greater than 5 mg/day of prednisone for at least 3 months. RESULTS: Amongst the 307 analysed patients (78% women, median RA duration: 8 years, mean DAS28-ESR: 5.1±1.3), 40% (95%CI=[35-46]) reached the targeted daily prednisone dose at M12, without conventional synthetic (cs)DMARD intensification. Predictive factors were RA duration of 5 years or less (OR=2.60, p=0.01), daily prednisone dose of 7.5 mg or less (OR=2.12, p=0.03), and low ESR value before the first TCZ infusion (OR=0.86, p=0.047). The proportion of patients with no more GCs increased up to 20% at M12. Disease activity improved over the 1-year period (DAS28-ESR LDA and remission in 41% and 33% of patients at M12, respectively). Amongst the 314 patients analysed for safety, at least one AE and at least one SAE were reported in 211 patients (67%) and in 48 patients (15%), respectively. No unexplained safety signal arose with TCZ. CONCLUSIONS: A biological DMARD as TCZ allows reducing both GCs dose and disease activity in RA patients. Nevertheless, corticosteroid spare in real life is probably lower.
25686607 Super-enhancers delineate disease-associated regulatory nodes in T cells. 2015 Apr 23 Enhancers regulate spatiotemporal gene expression and impart cell-specific transcriptional outputs that drive cell identity. Super-enhancers (SEs), also known as stretch-enhancers, are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease. CD4(+) T cells are critical for host defence and autoimmunity. Here we analysed maps of mouse T-cell SEs as a non-biased means of identifying key regulatory nodes involved in cell specification. We found that cytokines and cytokine receptors were the dominant class of genes exhibiting SE architecture in T cells. Nonetheless, the locus encoding Bach2, a key negative regulator of effector differentiation, emerged as the most prominent T-cell SE, revealing a network in which SE-associated genes critical for T-cell biology are repressed by BACH2. Disease-associated single-nucleotide polymorphisms for immune-mediated disorders, including rheumatoid arthritis, were highly enriched for T-cell SEs versus typical enhancers or SEs in other cell lineages. Intriguingly, treatment of T cells with the Janus kinase (JAK) inhibitor tofacitinib disproportionately altered the expression of rheumatoid arthritis risk genes with SE structures. Together, these results indicate that genes with SE architecture in T cells encompass a variety of cytokines and cytokine receptors but are controlled by a 'guardian' transcription factor, itself endowed with an SE. Thus, enumeration of SEs allows the unbiased determination of key regulatory nodes in T cells, which are preferentially modulated by pharmacological intervention.