International Journal of Rheumatology最新文献

We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.

Background: Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial.

Objective: To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group.

Methods: We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI).

Results: Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03).

Conclusions: Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs-celecoxib, etoricoxib, and diclofenac-using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.

Objectives: To assess the correlation between prednisone and methotrexate (MTX) treatment duration and dosage with the TST induration diameter of the TST reaction among rheumatoid arthritis (RA) patients.

Method: We retrospectively analyzed consecutive cases of RA patients who were TNF-i therapy candidates. TST measurements, prednisone and methotrexate dosages, and treatment durations were recorded. A control group was randomly selected from healthy subjects. We compared TST reaction size between the following three groups: RA patients with current prednisone treatment, RA prednisone naïve patients, and healthy individuals.

Results: Our study sample comprised 43 RA patients with prednisone treatment, 22 prednisone naïve patients, and 195 healthy subjects. There was no significant difference in mean TST between the groups (5.3±6.6, 7.8±6.2, and 7.6±7.0, respectively, p=0.149). No correlation was noted between TST size and prednisone u-y (r=0.229, p=0.140) or methotrexate u-y in patients with and without prednisone therapy (r=0.219, p=0.158; and r=-0.293, p=0.186, respectively).

Conclusions: Our results show that the TST reaction size among RA patients may not be affected by prednisone therapy. In addition, the TST reaction of RA patients may present similarly to that of healthy individuals. Therefore, we suggest that the criterion of a TST reaction of 5 mm to define latent TB infection in our population should be reevaluated.

Objective: Persistent infectious agents have been implicated in chronic and recurrent inflammation, which may trigger or worsen many types of arthritis. Our objective was to determine whether exposure to herpes simplex virus (HSV) and human papillomavirus (HPV) is associated with self-reported arthritis among US adults.

Methods: We used data from two consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 2009 until 2012 (N of examined adults ages 20-69 = 9483). Participants were classified as having arthritis by self-report. Viral serology for HSV-1 and HSV-2 and HPV PCR studies from oral rinse and vaginal swabs were available for analysis. We compared HSV-1 and HSV-2 seropositivity as well as oral and vaginal HPV DNA positivity between participants with self-reported arthritis vs. those without, adjusting for age, gender, race, income, education, BMI, and the use of immunosuppressive medications. We used three comparator outcomes, gout, kidney stones, and hypertension, to evaluate whether the associations were specific or not to arthritis.

Results: Arthritis was associated with older age, female gender, non-Hispanic White and Non-Hispanic Black race, higher BMI, and lower socioeconomic status. HSV-2 seropositivity, but not HSV-1 seropositivity, was independently associated with arthritis after adjustment for age, gender, race, income, education, BMI, and the use of immunosuppressive medications: AOR 1.48 (1.10-1.99). Oral HPV DNA positivity was also independently associated with arthritis: AOR 1.63 (1.17-2.28). After adjustment, there was no statistically significant difference in vaginal HPV DNA positivity between those with vs. those without arthritis: AOR 1.22 (0.90-1.66). There were no significant associations between viral exposures and any of the comparator outcomes.

Conclusions: HSV-2 seropositivity and oral HPV DNA positivity were associated with self-reported arthritis and not with comparator outcomes, after adjustment for multiple potential confounders. These findings should be confirmed in longitudinal studies.

Background: Red blood cell distribution width (RDW) is a routine hematologic parameter that is a predictor of cardiovascular disease (CVD) events and is independent of combined traditional risk factor scoring systems. The RDW has also been associated with rheumatic disease activity. Whether RDW is associated with traditional CVD risk factors or Atherosclerotic Cardiovascular Disease (ASCVD) 10-year CVD risk score in patients with seronegative spondyloarthritis with axial or peripheral disease has not been previously determined.

Methods: We performed a retrospective, chart review study evaluating the relationship between RDW, albumin, hemoglobin, C-reactive protein (CRP), absolute lymphocyte count (ALC), and ASCVD scoring parameters [age, hypertension status, diabetes mellitus (DM) status, lipid profile, and smoking status] in a cohort of spondyloarthritis patients, taking into consideration their HLA-B27 status, race, and treatment status.

Results: RDW was found to positively correlate with ASCVD 10-year score and age, and ASCVD score did not change over time after patients were treated for spondyloarthritis. Albumin was found to negatively correlate with ASCVD 10-year risk score. Both RDW and albumin correlated with CRP. ALC failed to correlate with ASCVD 10-year score but did show a tendency to be associated with CVD, CVD events, and cardiac conduction abnormalities.

Conclusions: These data indicate that further study is warranted to evaluate RDW, albumin level, and ALC as potential predictors of CVD in the spondyloarthritis patient population.

Objective. Systemic sclerosis (SSc) is a systemic connective tissue disease of unknown etiology. Aberrant gene expression and epigenetic modifications in circulating immune cells have been implicated in the pathogenesis of SSc. This study is to delineate the interaction network between gene transcription and DNA methylation in PBMC of SSc patients and to identify methylation-regulated genes which are involved in the pathogenesis of SSc. Methods. Genome-wide mRNA transcription and global DNA methylation analysis were performed on PBMC from 18 SSc patients and 19 matched normal controls (NC) using Illumina BeadChips. Differentially expressed genes (DEGs) and differentially methylated positions (DMPs) were integrative analyzed to identify methylation-regulated genes and associated molecular pathways. Results. Transcriptome analysis distinguished 453 DEGs (269 up- and 184 downregulated) in SSc from NC. Global DNA methylation analysis identified 925 DMPs located on 618 genes. Integration of the two lists revealed only 20 DEGs which harbor inversely correlated DMPs, including 12 upregulated (ELANE, CTSG, LTBR, C3AR1, CSTA, SPI1, ODF3B, SAMD4A, PLAUR, NFE2, ZYX, and CTSZ) and eight downregulated genes (RUNX3, PRF1, PRKCH, PAG1, RASSF5, FYN, CXCR6, and F2R). These potential methylation-regulated DEGs (MeDEGs) are enriched in the pathways related to immune cell migration, proliferation, activation, and inflammation activities. Using a machine learning algorism, we identified six out of the 20 MeDEGs, including F2R, CXCR6, FYN, LTBR, CTSG, and ELANE, which distinguished SSc from NC with 100% accuracy. Four genes (F2R, FYN, PAG1, and PRKCH) differentially expressed in SSc with interstitial lung disease (ILD) compared to SSc without ILD. Conclusion. The identified MeDEGs may represent novel candidate factors which lead to the abnormal activation of immune regulatory pathways in the pathogenesis of SSc. They may also be used as diagnostic biomarkers for SSc and clinical complications.

Objective: The aim of the present study was to assess the association between muscle strength, lower extremity function, employment status, and work ability in RA patients.

Methods: One hundred seropositive RA outpatients of working age were included in this cross-sectional study. Employment status was assessed by interview and work ability by the Work Ability Index-Single Item Scale (WAS). Muscle strength was determined using dynamometer measurement of isometric hand grip and knee extensor strength. Lower extremity function was measured using the short physical performance battery (SPPB). Regression models estimate the association between unemployment, work ability and muscle strength, and lower extremity function, controlling for sociodemographic and disease-related factors.

Results: Forty-one percent of the RA patients were not gainfully employed, and their median work ability had a good WAS value (7.00 [4.00-7.00]). Patients with better knee extensor strength (OR=1.07, 95% CI [1.02-1.12) and better physical performance (OR=1.71, 95% CI [1.18-2.49]) had a significantly better chance of gainful employment. The odds for hand grip strength remained significant when adjusted for sociodemographic (OR=1.5, 95% CI [1.00-1.09]), but not for disease-specific variables. Better hand grip strength (β=0.25, p=0.039) and better knee extensor strength (β=0.45, p=0.001) as well as better lower extremity function (SPPB) (β=0.51, p<0.001) remained significantly associated with work ability following adjustment for sociodemographic and disease-specific variables.

Conclusions: The association of employment status and work ability with parameters of physical fitness suggests that improvement in muscle strength and lower extremity function may positively influence work ability and employment in individuals with RA.

Objectives: Although wrist arthrodesis using a plate is an established treatment with a well-documented successful union rate for severely destroyed wrists, plate-related complications are a matter of great concern.

Methods: We retrospectively compared wrist arthrodesis using an AO wrist fusion plate in nine and a locking compression plate (LCP) metaphyseal plate in seven cases of rheumatoid arthritis.

Results: The mean follow-up was 40.6 months in the AO wrist fusion plate group and 57.2 months in the LCP metaphyseal plate group. Bone union at the arthrodesis site was achieved in all cases in both groups. Comparison of the original position of the fusion on the immediate postoperative radiographs and the position on the most recent follow-up radiographs demonstrated good stability in both groups. Plate-related complications occurred in four cases in the AO wrist fusion plate group and no cases in the LCP metaphyseal plate group. Complications included pain over the plate, wound dehiscence and infection, extensor tendon adhesion, and fracture in one case each.

Conclusion: Wrist arthrodesis using an LCP metaphyseal plate was favorable for rheumatoid arthritis patients with comparable stability to that of and a lower risk of plate-related complications than an AO wrist fusion plate.