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ID PMID Title PublicationDate abstract
25632482 The anti-rheumatoid arthritis property of the folk medicine Dianbaizhu (Gaultheria leucoca 2014 Dec The Chinese folk medicine Dianbaizhu, consisting of Gaultheria species, is widely used for the treatment of rheumatoid arthritis by several minority nationalities. The species and plant parts of this genus used as Dianbaizhu in clinical application are confused. In order to elucidate the species and the medicinal parts, as well as to ascertain the effective components and the probable optimal source of Dianbaizhu, the different plant parts and polarity fractions of its mainstream species, G. leucocarpa var. yunnanensis were investigated. The inhibition of nitric oxide and tumor necrosis factor produced in macrophage J774 were used to assess the anti-inflammatory effect of those samples. G. leucocarpa var. yunnanensis may be the preferred species for anti-RA effect. The underground parts of this taxon showed the best anti-inflammatory and anti-RA activities; the n-butanol and water fractions of the underground parts may be the most anti-RA active.
24663105 Contraception and pregnancy counselling in rheumatoid arthritis. 2014 May PURPOSE OF REVIEW: The purpose of this study is to encourage discussion of reproduction issues in all patients of fertile age in order to prevent unplanned and ill-timed pregnancies in patients with rheumatoid arthritis (RA). RECENT FINDINGS: Counselling patients who desire children requires consideration of relevant reproductive health issues, including fertility, interaction of pregnancy and RA, and management during pregnancy and lactation. RA patients have no disease-related restrictions in regard to contraception, but need to be counselled on safe birth control particularly during treatment with potentially teratogenic drugs. In spite of mostly beneficial effects of pregnancy on RA, active disease and aggressive drug treatment can impair pregnancy outcomes. Options for drug therapy, though limited, may help to maintain low disease activity during pregnancy and lactation. SUMMARY: Careful preconception counselling and risk assessment is important in RA women, with a particular focus on preventing unplanned pregnancy by information on contraception. Antibody status and all medications need to be reviewed before pregnancy. Maintaining low disease activity before and during pregnancy is crucial for good outcomes. Preconceptional counselling shared with all health professionals engaged in the care of a patient helps to ensure healthy pregnancy outcomes for mother and child.
23287598 Podoplanin is an inflammatory protein upregulated in Th17 cells in SKG arthritic joints. 2013 Jun Interleukin 17-producing helper T (Th17) cells play pathogenic roles in chronic inflammatory and autoimmune diseases, including arthritis, colitis and multiple sclerosis. Th17 cells selectively express the transcription factor RORγt, as well as the cytokine receptors IL-23R and CCR6. Identification of novel Th17 cell-specific molecules may have potential value as diagnostic markers in the above-mentioned inflammatory diseases. To that aim, we carried out a comparative microarray analysis on in vitro differentiated Th1, Th2, Treg and Th17 cells from naïve CD4(+) cells of BALB/c mice. Among a total of one hundred and twenty Th17 cell-specific molecules, twenty-nine were novel cell-surface molecules. Then we revealed that thirteen of them were up-regulated in vivo in inflamed tissues from experimental autoimmune diseases, including spontaneous SKG arthritis, inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE). Next, we analyzed the expression of four membranous molecules, and revealed that podoplanin was expressed highly in the in vitro differentiated Th17 cells. Moreover, at the inflamed synovium of the arthritic SKG mice, most of the accumulating Th17 cells were podoplanin-positive. These results indicate that podoplanin would be a useful Th17 cell marker for diagnosing pathological conditions of autoimmune diseases, including rheumatoid arthritis.
23676505 Methotrexate therapy leading to a rapid progression of a previously indolent prostate canc 2014 Apr Methotrexate therapy has been associated with occurrence and/or accelerated progression of malignancies. We describe a patient who developed widespread bone metastases of a previously confined to the prostate gland prostate cancer shortly after starting methotrexate therapy for rheumatoid arthritis and large granular lymphocyte leukemia. We believe an immunosuppressive milieu brought on by the methotrexate use in this case is responsible for the rapid progression of prostate cancer leading to the patient's demise. To the best of our knowledge, no association has been made to date between the therapy with methotrexate and a fulminant course of a previously indolent prostate cancer. Given its utilization in a variety of benign and malignant conditions and the ageing population, caution is advised with the use of this agent, especially in the presence of an underlying malignancy.
24889761 Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccin 2014 Oct Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies contribute to the low rate of influenza infection seen in RA patients. Twenty RA patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received trivalent influenza subunit vaccination. Before and 28 days after vaccination, H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor (BAFF) levels were determined in serum samples before vaccination. Vaccination induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against both strains in the HC and MTX groups (all P < 0·01), but not in the RTX group. HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX late patients (RTX treatment 6-10 months before vaccination), IgG (IgG1 and IgG3) response to vaccination was restored, but not IgM response. BAFF levels were significantly increased in RA-RTX patients and correlated with total IgG levels. Haemagglutination inhibition assay, used as gold standard, detects primarily IgG (IgG1) responses. IgM- and IgG influenza-specific antibodies increase after vaccination in HC and RA patients except in patients on RTX treatment. BAFF levels are increased in both early and late RTX-treated patients, but do not correlate with an influenza-specific antibody response.
23877585 Difference in method of administration did not significantly impact item response: an IRT- 2014 Feb PURPOSE: To test the impact of method of administration (MOA) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: Two non-overlapping parallel 8-item forms from each of three PROMIS domains (physical function, fatigue, and depression) were completed by 923 adults (age 18-89) with chronic obstructive pulmonary disease, depression, or rheumatoid arthritis. In a randomized cross-over design, subjects answered one form by interactive voice response (IVR) technology, paper questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC) on the Internet, and a second form by PC, in the same administration. Structural invariance, equivalence of item responses, and measurement precision were evaluated using confirmatory factor analysis and item response theory methods. RESULTS: Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA. Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA. CONCLUSIONS: We found no statistically or clinically significant differences in score levels in IVR, PQ, or PDA administration as compared to PC. Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis.
25488782 Adverse effects of TNF inhibitors in SpA: are they different from RA? 2014 Oct Tumor necrosis factor (TNF) inhibitors were the first biologic drugs prescribed for the treatment of spondyloarthritis (SpA) and rheumatoid arthritis (RA). Although they provide significant improvement of signs and symptoms, TNF inhibitors need to be used frequently for a long period of time. The analysis of the follow-up of the largest national biologics registries has shown that the most important adverse effect of TNF inhibitors is infection, which is significantly higher than the non-biologic treatment group; reactivation of latent tuberculosis is three to four times more frequent in patients using monoclonal antibodies than soluble receptors. The only cancer site more frequent to be associated with TNF inhibitors in RA and SpA is the non-melanoma skin cancer. Paradoxical reactions do occur during anti-TNF treatment mainly in SpA, such as new manifestations or flares of acute uveitis, new onset of psoriasis, such as palmoplantar pustulosis, or new onset or flares of inflammatory bowel disease, which occurs especially during etanercept treatment.
24842476 Early response to certolizumab pegol predicts long-term outcomes in patients with active r 2015 Jan OBJECTIVES: A post-hoc analysis was performed to determine the relationship between the timing and magnitude of DAS28(ESR) response and long term outcomes in Japanese patients after 1 year of CZP treatment. METHODS: Our analysis included 82 J-RAPID trial patients treated with CZP 200 mg and methotrexate, and 116 HIKARI trial patients treated with CZP 200 mg alone or with disease-modifying agents other than methotrexate. Remission rates and changes in mTSS at year 1 were compared to the DAS28(ESR) response at week 12 of CZP treatment. RESULTS: After 1 year of treatment, remission was achieved in 41.3% of the J-RAPID and 34.9% of the HIKARI patients with a week 12 DAS28(ESR) response of ≥ 1.2. In comparison, patients with a DAS28(ESR) response of < 1.2 at week 12 only had a < 7% probability of achieving remission and displayed higher change in mTSS after 1-year treatment. CONCLUSIONS: The likelihood of remission and extent of radiographic progression after 1 year was associated with the week 12 DAS28(ESR) response. The DAS28(ESR) response at 12 weeks could be beneficial for identifying patients that are unlikely to respond to prolonged CZP treatment.
23696745 Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 si 2013 May Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10(-9)). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10(-9)), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA-approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in complex traits such as RA.
25057178 Being overweight or obese and risk of developing rheumatoid arthritis among women: a prosp 2014 Nov OBJECTIVES: To examine the relationship between being overweight or obese and developing rheumatoid arthritis (RA) in two large prospective cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). METHODS: We followed 109 896 women enrolled in NHS and 108 727 in NHSII who provided lifestyle, environmental exposure and anthropometric information through biennial questionnaires. We assessed the association between time-varying and cumulative Body Mass Index (BMI) in WHO categories of normal, overweight and obese (18.5-<25, 25.0-<30, ≥30.0 kg/m(2)) and incident RA meeting the 1987 American College of Rheumatology (ACR) criteria. We estimated HRs for overall RA and serologic subtypes with Cox regression models adjusted for potential confounders. We repeated analyses restricted to RA diagnosed at age 55 years or younger. RESULTS: During 2 765 195 person-years of follow-up (1976-2008) in NHS and 1 934 518 person-years (1989-2009) in NHSII, we validated 1181 incident cases of RA (826 in NHS, 355 in NHSII). There was a trend toward increased risk of all RA among overweight and obese women (HR (95% CI) 1.37 (0.95 to 1.98) and 1.37 (0.91, 2.09), p for trend=0.068). Among RA cases diagnosed at age 55 years or younger, this association appeared stronger (HR 1.45 (1.03 to 2.03) for overweight and 1.65 (1.34 to 2.05) for obese women (p trend <0.001)). Ten cumulative years of being obese, conferred a 37% increased risk of RA at younger ages (HR 1.37 (1.11 to 1.69)). CONCLUSIONS: Risks of seropositive and seronegative RA were elevated among overweight and obese women, particularly among women diagnosed with RA at earlier ages.
25167369 The window of opportunity: a relevant concept for axial spondyloarthritis. 2014 The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.
24824076 Pharmacology of intra-articular triamcinolone. 2014 Aug INTRODUCTION: The inflammatory joint diseases of juvenile inflammatory arthritis (JIA), rheumatoid arthritis (RA) and osteoarthritis (OA): and also mild to moderate joint injury, all require a multidisciplinary approach to management. Intra-articular injections of corticosteroids have been shown to be a very beneficial adjunctive treatment in the management of the above disorders. It is, therefore, important that clinicians have a good understanding of the clinical actions of intra-articular injections. OBJECTIVE: This article explores the pharmacokinetics, pharmacodynamics, and clinical pharmacology of triamcinolone acetonide (TA) and triamcinolone hexacetonide (TH) in JIA, RA, and OA. METHODS: Literature search of TA and TH articles was conducted using key word searches in the PubMed and Google Scholar databases and through references within found articles. RESULTS: TA and TH intra-articular injections have been shown to provide good clinical benefit for up to 6 months and even longer. TH has been shown to decrease in the expression of citrullinated proteins, the monoclonal antibody F95, and peptidylarginine deiminase 4 in RA synovium. TA and TH intra-articular injections have a low side effect profile which is similar to other corticosteroid. They have minimal to no mineralocorticoid adverse effects and facial flushing 2-3 days post injections is the most common side effect recorded, and in almost all cases is no worse than nuisance. CONCLUSION: TA and TH are useful adjunct therapies in the management of JIA, RA, OA, and mild to moderate joint injury.
24886600 A genetic variant in osteoprotegerin is associated with progression of joint destruction i 2014 May 7 INTRODUCTION: Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necrosis factor (TNF) receptor associated factor-6), and osteoclast formation ultimately leading to enhanced bone resorption. This bone resorption is inhibited by osteoprotegerin (OPG) which prevents RANKL-RANK interactions. The OPG/RANK/RANKL/TRAF6 pathway plays an important role in bone remodeling. Therefore, we investigated whether genetic variants in OPG, RANK, RANKL and TRAF6 are associated with the rate of joint destruction in RA. METHODS: 1,418 patients with 4,885 X-rays of hands and feet derived from four independent data-sets were studied. In each data-set the relative increase of the progression rate per year in the presence of a genotype was assessed. First, explorative analyses were performed on 600 RA-patients from Leiden. 109 SNPs, tagging OPG, RANK, RANKL and TRAF6, were tested. Single nucleotide polymorphisms (SNPs) significantly associated in phase-1 were genotyped in data-sets from Groningen (Netherlands), Sheffield (United Kingdom) and Lund (Switzerland). Data were summarized in an inverse weighted variance meta-analysis. Bonferonni correction for multiple testing was applied. RESULTS: We found that 33 SNPs were significantly associated with the rate of joint destruction in phase-1. In phase-2, six SNPs in OPG and four SNPs in RANK were associated with progression of joint destruction with P-value <0.05. In the meta-analyses of all four data-sets, RA-patients with the minor allele of OPG-rs1485305 expressed higher rates of joint destruction compared to patients without these risk variants (P = 2.35x10-4). This variant was also significant after Bonferroni correction. CONCLUSIONS: These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA.
24623718 A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal 2014 Jul OBJECTIVE: To evaluate ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics-naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: In this phase II, randomized, double-blind study, placebo or ixekizumab was administered subcutaneously to 260 biologics-naive patients and 188 patients with an inadequate response to TNF inhibitors at weeks 0, 1, 2, 4, 6, 8, and 10 with concomitant disease-modifying antirheumatic drugs. The primary objective was to determine the dose-response relationship of ixekizumab as measured by the proportion of biologics-naive patients meeting the American College of Rheumatology 20% improvement criteria (ACR20) at week 12. RESULTS: Using a logistic regression model defined a priori, a statistically significant dose-response relationship as measured by ACR20 response rates at week 12 was detected in biologics-naive patients (P = 0.031). For patients with an inadequate response to TNF inhibitors, ACR20 responses at week 12 were significantly better with ixekizumab than placebo (P < 0.05). Decreases in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), Clinical Disease Activity Index (CDAI), and CRP level from baseline were observed at week 12 in the ixekizumab groups in both populations (P < 0.05 versus placebo). Onset of action was rapid in some dose groups in both populations, with improvements in the ACR20, DAS28-CRP, CRP levels, and CDAI observed by day 3 (P < 0.05). Adverse events occurred with similar frequencies overall in the ixekizumab and placebo groups. Infections were more frequent with ixekizumab than placebo (biologics-naive 25% versus 19%; inadequate responders to TNF inhibitors 27% versus 25%). No mycobacterial or invasive fungal infections were reported. CONCLUSION: Ixekizumab improved RA signs and symptoms in RA patients who were either naive to biologics treatment or had an inadequate response to TNF inhibitors. The safety profile was similar to that of other biologic agents, with no unexpected safety concerns.
24460746 Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years 2014 Jan 27 INTRODUCTION: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise. METHODS: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3. RESULTS: Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation. CONCLUSIONS: Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation. TRIAL REGISTRATION: NCT00448383, NCT00234884.
23388693 Purification of human immunoglobulin G autoantibodies to tumor necrosis factor using affin 2013 Apr 30 Autoantibodies to cytokines are important biological effector molecules that can regulate cytokine activities. The aim of the study was to develop a protocol to purify autoantibodies to tumor necrosis factor from human serum, for use as a calibration material to determine the absolute content of autoantibodies to tumor necrosis factor by enzyme-linked immunosorbent assay. The proposed protocol includes a set of affinity chromatography methods, namely, Bio-Gel P6DG sorbent to remove albumin from serum, Protein G Sepharose 4 Fast Flow to obtain a total immunoglobulin G fraction of serum immunoglobulins, and Affi-Gel 15 to obtain specifically antibodies to tumor necrosis factor. The addition of a magnetic separation procedure to the protocol eliminated contaminant tumor necrosis factor from the fraction of autoantibodies to tumor necrosis factor. The protocol generated a pure fraction of autoantibodies to tumor necrosis factor, and enabled us to determine the absolute concentrations of different subclasses of immunoglobulin G autoantibodies to tumor necrosis factor in apparently healthy donors.
24313916 Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthrit 2014 Sep OBJECTIVES: This 24-week, multicenter, double-blind, randomized, placebo-controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese rheumatoid arthritis (RA) patients with inadequate response to MTX. METHODS: In total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400 mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12. RESULTS: ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and 61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and placebo groups, respectively, with statistical significance between each CZP group and placebo. Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related quality of life (HRQoL) were observed in all three CZP groups vs placebo. Incidence of adverse events was similar between CZP groups. CONCLUSIONS: CZP plus MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX, with significant inhibition of radiographic progression and improved HRQoL.
25047021 Analysis of infections and all-cause mortality in phase II, phase III, and long-term exten 2014 Nov OBJECTIVE: To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA). METHODS: Pooled data from studies of tofacitinib in patients with RA were analyzed. In these studies, tofacitinib was administered as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs. The cutoff date for inclusion of data was April 19, 2012. RESULTS: Across phase II, phase III, and LTE studies, 4,789 patients received tofacitinib (8,460 patient-years of exposure). The overall rate of serious infection was 3.09 events per 100 patient-years (95% confidence interval [95% CI] 2.73-3.49), and rates were stable over time. A Cox proportional hazards model showed that age, corticosteroid dose, diabetes, and tofacitinib dose were independently linked to the risk of serious infection. Lymphocyte counts of <0.5 × 10(3) /mm(3) were rare but were associated with an increased risk of treated and/or serious infection. Overall, all-cause mortality rates were 0.30 events per 100 patient-years (95% CI 0.20-0.44). CONCLUSION: The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time.
24728331 Predicting the development of clinical arthritis in anti-CCP positive individuals with non 2015 Sep OBJECTIVES: To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group. METHODS: In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation. FINDINGS: 100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range 0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0-1; 0/11 progressed). CONCLUSIONS: In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention. TRIAL REGISTRATION NUMBER: NCT02012764 at ClinicalTrials.gov.
25339123 An Internet-based technique for the identification of persons with symptoms of inflammator 2015 Mar Identifying persons with early rheumatoid arthritis (RA) is a major challenge. The role of the Internet in making decisions about seeking care has not been studied. We developed a method for early diagnosis and referral using the Arthritis Foundation's website. A person with less than 3 months of joint pain symptom who has not yet sought medical attention was screened. Prescreened persons are linked to a self-scoring questionnaire and get a "likelihood" of RA statement. If "likely," the person is offered a free evaluation and biomarker testing performed by Quest Diagnostics. The system available only to Massachusetts's residents yielded a small steady flow of screen-positive individuals. Over 21 months, 43,244 persons took the Arthritis Foundation website prescreening questionnaire; 196 were from Massachusetts and 60 took the self-scoring algorithm. Of the 48 who screened positive, 29 set up an appointment for a free evaluation, but six never came in. Twenty-four subjects were evaluated and diagnosed independently by three rheumatologists. One met the 1987 American College of Rheumatology (ACR) criteria for RA and two met the 2010 ACR/EULAR RA criteria. The 24 examined individuals were contacted at a minimum of 1 year and asked to redo the case-finding questionnaire and asked about their health resource utilization during the interval. Seventeen of the 24 subjects responded, and 10 had seen a health professional. Three of the 17 had a diagnosis of RA; all were on at least methotrexate. Internet case finding was useful in identifying new potential RA cases. The system's performance characteristics are theoretically limited only by the number of study sites available. However, the major barrier may be that seeing a health professional is not a priority for many individuals with early symptoms.