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ID PMID Title PublicationDate abstract
26678745 Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the I 2015 Dec 18 Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case-control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date-matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41-0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects.
24608404 Risk of hospitalised infection in rheumatoid arthritis patients receiving biologics follow 2015 Jun BACKGROUND: The risk of subsequent infections in rheumatoid arthritis (RA) patients who receive biologic therapy after a serious infection is unclear. OBJECTIVE: To compare the subsequent risk of hospitalised infections associated with specific biologic agents among RA patients previously hospitalised for infection while receiving anti-tumour necrosis factor (anti-TNF) therapy. METHODS: Using 2006-2010 Medicare data for 100% of beneficiaries with RA enrolled in Medicare, we identified patients hospitalised with an infection while on anti-TNF agents. Follow-up began 61 days after hospital discharge and ended at the earliest of: next infection, loss of Medicare coverage or 18 months after start of follow-up. We calculated the incidence rate of subsequent hospitalised infection for each biologic and used Cox regression to control for potential confounders. RESULTS: 10 794 eligible hospitalised infections among 10183 unique RA patients who contributed at least 1 day of biologic exposure during follow-up. We identified 7807 person-years of exposure to selected biologics--333 abatacept, 133 rituximab and 7341 anti-TNFs (1797 etanercept, 1405 adalimumab, 4139 infliximab)--and 2666 associated infections. Mean age across biologic exposure cohorts was 64-69 years. The crude incidence rate of subsequent hospitalised infection ranged from 27.1 to 34.6 per 100 person-years. After multivariable adjustment, abatacept (HR: 0.80, 95% CI 0.64 to 0.99) and etanercept (HR: 0.83, 95% CI 0.72 to 0.96) users had significantly lower risks of subsequent infection compared to infliximab users. CONCLUSIONS: Among RA patients who experienced a hospitalised infection while on anti-TNF therapy, abatacept and etanercept were associated with the lowest risk of subsequent infection compared to other biologic therapies.
27895064 Risk of obstructive sleep apnoea in patients with rheumatoid arthritis: a nationwide popul 2016 Nov 28 OBJECTIVE: Sleep disorders are prevalent medical disorders in patients with rheumatoid arthritis (RA). However, whether patients with RA are at an increased risk of developing obstructive sleep apnoea (OSA) is unclear. DESIGN: Using population-based retrospective cohort study to examine the risk of OSA in patients with RA. SETTING: We used claims data of the National Health Insurance Research Database (NHIRD) of Taiwan. PARTICIPANTS: We identified a RA cohort with 33 418 patients newly diagnosed in 2000-2010 and a randomly selected non-RA comparison cohort with 33 418 individuals frequency matched by sex, age and diagnosis year. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident OSA was estimated by the end of 2011. The HRs of OSA were calculated using the Cox proportional hazards regression analysis. RESULTS: The overall incidence rate of OSA was 75% greater in the RA cohort than in the non-RA cohort (3.04 vs 1.73/10 000 person-years, p<0.001), with an adjusted HR (aHR) of 1.75 (95% CI 1.18 to 2.60). Stratified analyses by sex, age group and comorbidity revealed that the incidence rates of OSA associated with RA were higher in all subgroups. CONCLUSIONS: This population-based retrospective cohort study suggested that patients with RA should be monitored for the risk of developing OSA.
27561645 Discovery of New Benzothiazine Derivative as Modulator of Pro- and Anti-inflammatory Cytok 2016 Dec The anti-inflammatory activities of benzothiazine and pyrazole derivatives are well documented. A series of novel N'-arylmethylidene-2-(3,4-dimethyl-5,5-dioxidopyrazolo(4,3 c)(1,2) benzothiazin-2(4H)yl) acetohydrazide compounds were previously synthesized by combining benzothiazine and pyrazole moieties into a single nucleus. The current study investigates the anti-arthritic potential of 3-ethoxy-4-hydroxyphenyl derivative (EHP) and its possible mechanism in arthritic rat model. Sprague-Dawley rats were induced rheumatoid arthritis with Freund's complete adjuvant and treated with EHP and piroxicam. At the end of the study, arthritic score was calculated, and ankle joint histopathology was performed using hematoxylin and eosin staining. Real-time reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine mRNA expression and protein levels of various inflammatory markers, respectively. In vitro concanavalin A (ConA)-stimulated splenocyte proliferation was measured. Serum levels of C-reactive protein (CRP), urea, creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were also determined. EHP significantly attenuated macroscopic arthritic score, joint histopathological lesions, and CRP levels. Treatment with EHP significantly reduced pro-inflammatory tissue necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin-17 (IL-17), and prostaglandin-E2 (PGE2) levels and increased the levels of anti-inflammatory interleukin-4 (IL-4) and interleukin-10 (IL-10). ConA-stimulated splenocyte proliferation was also significantly suppressed by treatment with EHP. Normalizing all hematological markers and ALP levels, EHP did not display any sign of nephrotoxicity and hepatotoxicity as determined by urea, creatinine, ALT, and AST levels. In conclusion, EHP possesses significant anti-arthritic property which may be attributed to its anti-inflammatory and immunomodulatory effects.
27125674 CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians. 2016 Jun OBJECTIVE: Limited data are available on the genetics of rheumatoid arthritis (RA) in Egyptians. Therefore, we investigated whether the confirmed genetic risk factors for RA in Europeans and/or Asians contribute to RA susceptibility in Egyptians. SUBJECTS AND METHODS: A set of seven single-nucleotide polymorphisms (SNPs) in the vicinity of CD28, TNFAIP3, PTPN22, PADI4 and HLA-DRA were tested in a large multi-centric RA cohort in Egypt, consisting of 394 cases and 398 matched controls. Patients were stratified based on the positivity of either anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor (RF). RESULTS: Significant association was evident for three SNPs in this cohort: the CD28 (rs1980422) variant showed a strong association in the whole cohort (P=0.000119) and in seropositive subsets of the disease (PACPA+=0.004; PRF+=0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (PACPA+=0.00573) and negative (PACPA-=0.00999) phenotypes, respectively. CONCLUSION: Our results suggest that CD28(rs1980422) and PTPN22(rs2476601) contribute to RA-susceptibility in Egyptians. Failure to replicate the association of PADI4(rs2240340)/(PADI4_94) in Egyptian RA patients provides further support for the notion that genetic architecture of RA is different in multiple populations of European, Asian, African, and Middle Eastern ancestries. Further investigation using large-scale studies is thus needed to maximize the power of genetic association.
27988813 Cardiovascular risk assessment in patients with rheumatoid arthritis: a correlative study 2017 Apr This study aimed to determine the relationship between noninvasive measures of arterial health and both estimated 10-year cardiovascular risk and measures of disease activity over time in established rheumatoid arthritis. Fifty rheumatoid arthritis patients underwent noninvasive arterial health testing (brachial artery reactivity, aortic augmentation index [AIx], pulse wave velocity, carotid artery intima-media thickness, and carotid artery plaque presence) and assessment of clinical disease activity (tender or swollen joint counts, Clinical Disease Activity Index [CDAI], and Health Assessment Questionnaire II [HAQ-II]). Clinical measures during 3 years before the study visit were averaged. Arterial health testing was compared with the American Heart Association/American College of Cardiology (AHA/ACC) Pooled Cohort Equation. Spearman methods identified correlations between disease activity measures, cardiac biomarkers, and arterial health parameters. Among the patients (mean age, 57.5 years), disease activity was moderate (mean [SD] CDAI, 16.9 [15.3]). At the study visit, corrected aortic augmentation index correlated with CDAI (r = 0.37, P = .009) and HAQ-II (r = 0.33, P = .02). AIx correlated with time-averaged tender joint count (r = 0.37, P = .008), CDAI (r = 0.36, P = .01), HAQ-II (r = 0.36, P = .01), swollen joint count (r = 0.36, P = .10), patient global assessment (r = 0.33, P = .02), physician global assessment (r = 0.35, P = .01), and pain score (r = 0.38, P = .007). The AHA/ACC low-risk group (<5% 10-year risk) had highest prevalence of carotid plaques. Arterial health testing may identify increased risk of cardiovascular disease compared with risk obtained through AHA/ACC Pooled Cohort Equation. Measures of arterial stiffness correlate with the burden of disease activity over time.
27317492 Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients 2017 Jul OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies. MATERIALS AND METHODS: Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported. RESULTS: The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population. CONCLUSION: In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib study population.
28005106 Mycotic Septic Arthritis of the Ankle Joint. 2016 Nov/Dec Septic arthritis is a debilitating acute orthopedic emergency. Unfortunately, the diagnosis can be delayed or missed in immunocompromised patients with diabetes mellitus, and the result can be catastrophic. These patients are also at risk for atypical infections, including mycotic subtypes, which are more insidious than their more aggressive, more common Staphylococcus counterparts. The result is increased morbidity. In this article, we report a case of Candida albicans septic arthritis in a patient with diabetes mellitus and rheumatoid arthritis. Her case highlights the complexities of this specific disease entity. With early diagnosis, treatment is multimodal, involving surgical débridement and prolonged antifungal therapy.
27894284 Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced a 2016 Nov 29 BACKGROUNDS: Patients with rheumatoid arthritis (RA) have increased risk of sudden cardiac death (SCD), which is two-fold higher than general population. The driving cause of SCD was considered due to lift-threatening arrhythmia where systemic inflammation acts as the pathophysiological basis linking RA to autonomicdysfunction. METHODS: To assess the sympathetic over-activity of "inflammatory reflex", we measured heart rate variability (HRV) in a rat collagen-induced arthritis (CIA) model, whose arthritis is induced in Lewis rats by intradermal injection of emulsion of type II collagen. Single-lead electrocardiogram (ECG) was recorded for 30 min every two days. Time and frequency-domain parameters, detrended fluctuation analysis (DFA), deceleration (DC) and acceleration capacity (AC) were analyzed. RESULTS: Compared with 9 control rats, many of HRV parameters of 9 CIA rats revealed significant different. At the beginning of arthritis, LF/HF was significant higher than controls (1st week: 2.41 ± 0.7 vs. 1.76 ± 0.6, p < 0.05; 2nd week: 2.24 ± 0.5 vs. 1.58 ± 0.5, p < 0.05) indicating intensive inflammatory reflex at the initial phase of inflammation but no significant difference was observed in the following recover phase. The similar trend of DFA parameters was noted. However, the DC appeared progressive lower despite of no significant increase of the LF/HF compared with controls since 4th week. CONCLUSIONS: We observed sympathetic over-activation of inflammatory reflex during early stage of arthritis in CIA rats. The ongoing decline of DC indicated advanced cardiac autonomic dysfunction regardless of remission of acute arthritis.
27143527 [Assessment of an intervention on cardiovascular risk factors in patients with rheumatoid 2016 Aug 5 OBJECTIVES: To evaluate the effectiveness of an intervention on cardiovascular risk factors (CVRF) in patients with rheumatoid arthritis. METHODS: After determining their CVRF and cardiovascular risk (CVR) by modified SCORE, we gave the patients a letter for their general practitioners in which they were requested for their cooperation in controlling CVRF and where the therapeutic goal for LDL cholesterol was specified. Three months later, any therapeutic intervention was recorded as well as the results. RESULTS: We included 211 patients, 29% with a high CVR. There were new diagnoses of CVRF in 100 patients (47%). The general practitioner changed the treatment in 2/12 diabetes, 30/84 HBP, 74/167 with elevation of LDL cholesterol and 21/51 with hypertriglyceridemia. The percentage of patients with good control over CVRF was: a) in HBP, 25 to 73%; b) elevation of LDL cholesterol from 10 to 17%; and c) in hypertriglyceridemia, 25 to 38%. CONCLUSIONS: Through this intervention, a new CVRF was diagnosed in nearly half of the patients. The effectiveness of the intervention on CVRF was low.
26666737 The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Art 2016 Sep BACKGROUND: Elevated neutrophil count is associated with poor prognosis and increased mortality in many conditions. Neutrophil to lymphocyte ratio (NLR) has emerged as a marker of inflammation in neoplastic and cardiovascular disorders. Herein, we investigated utility of this simple tool in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study consisted of 136 RA and 140 AS patients, along with 117 healthy control subjects. RA and AS activities were determined with Disease Activity Score (DAS) and Bath Ankylosing Spondylitis Disease Activity indices (BASDAI), respectively. The association between NLR and disease activity was analyzed. RESULTS: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neutrophil counts were significantly higher in RA and AS patients compared to healthy controls. Similarly, NLR was higher compared to control subjects, both in RA (2.53 ± 1.4 vs. 2.16 ± 1.0, P = 0.019) and AS (2.43 ± 1.4 vs. 2.16 ± 1.0, P = 0.077). NLR correlated well with ESR and CRP, both in RA and AS. Moreover, NLR increased across worsening DAS28 activity groups (2.1 ± 1.0 in patients with remission, 2.5 ± 1.0 in low-moderate, 3.8 ± 2.5 in high disease activity). However, no association was found between NLR and BASDAI. CONCLUSION: NLR is a cheap and readily available marker for the assessment of disease activity in RA.
26834222 Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheu 2016 May OBJECTIVE: To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. METHODS: Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. RESULTS: Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. CONCLUSION: The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.
26815184 [Effect of 10-hydroxycamptotbecine on the expression of VEGF in rheumatoid arthritis synov 2015 Sep 15 OBJECTIVE: To study the effect of 10-Hydroxycamptotbecine (10-HCPT) on the expression of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: RASFs were isolated form synovial tissue of RA patients and cultured in vitro. 10-HCPT (3.0×10(-6) mol/L, 3.0×10(-5) mol/L) and Methotrexate (MTX) (2.0×10(-6) mol/L, 2.0×10(-5) mol/L) with different concentrations were used to treat RASFs for 48 hours, and RASFs without 10-HCPT and MTX treatment were served as the control group. The level of VEGF in the supernatant of RASFs culture was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with control group, high and low dose 10-HCPT groups showed significant values on the effect of inhibiting the expression of VEGF in RASFs. Compared with low-dose MTX group, both high and low dose 10-HCPT groups showed significant difference (P<0.05); compared with high-dose MTX group, the high-dose 10-HCPT group had significant difference (P<0.05). CONCLUSION: Compared with MTX, 10-HCPT showed significant effect on inhibiting the expression of VEGF in RASFs.
25877497 Disease Severity and Pregnancy Outcomes in Women with Rheumatoid Arthritis: Results from t 2015 Aug OBJECTIVE: To determine the effect of rheumatoid arthritis (RA) disease severity on pregnancy outcomes in pregnant women with and without autoimmune diseases. METHODS: A prospective cohort study was conducted using the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project. Pregnant women with RA enrolled between 2005 and 2013 were selected if they (1) delivered a live-born singleton infant; and (2) completed 3 telephone-based measures of RA disease severity prior to 20 weeks' gestation, including the Health Assessment Questionnaire Disability Index (HAQ-DI), pain score, and patient's global scale. Associations between RA disease severity and preterm delivery, small for gestational age (SGA), or cesarean delivery were tested in unadjusted and multivariate analyses using modified Poisson regression models. RESULTS: The sample consisted of 440 women with RA. Several unadjusted comparisons yielded significant associations. After adjustment for covariates, increasing disease severity was associated with risk for preterm delivery and SGA. For each unit increase in HAQ-DI (0-1), the adjusted relative risk (aRR) for preterm delivery increased by 58% (aRR 1.58, 95% CI 1.17-2.15). Among those with HAQ-DI > 0.5, the aRR for SGA was 1.81 (95% CI 1.01-3.33). CONCLUSION: RA disease severity in early pregnancy, as measured in this study, was predictive of preterm delivery and SGA. These findings suggest that the risk of preterm delivery and SGA in women with RA might be lowered if RA is well controlled early in pregnancy.
25939523 Tumor necrosis factor-α antagonist therapy for concomitant rheumatoid arthritis and hepat 2015 Jun The aim of this study was to investigate treatment response and hepatic safety of anti-tumor necrosis factor-α therapy among patients with concomitant rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We reviewed the charts of 101 consecutive RA patients who were eligible for anti-TNF-α therapy in the Chiayi Branch of Chang Gung Memorial Hospital. Group A patients were sero-positive for anti-HCV antibodies and had HCV RNA but were negative for hepatitis B surface antigen (HBsAg). Group B (the control group) patients were sero-negative for both anti-HCV antibodies and HBsAg. Response to anti-TNF-α treatment was assessed by calculating disease activity score at 28 joints (DAS28) at baseline and 5, 8, and 11 months after the start of TNF-α antagonist therapy. Percentage change in DAS28 from baseline to month 5 was 21.36 ± 8.01 % in group A and 26.98 ± 10.43 % in group B (p = 0.011). However, there was no obvious difference in treatment response between groups at other time points. Anti-TNF-α therapy was discontinued within 1 year of starting treatment in two subjects in group A and 4 in group B. Response to anti-TNF-α was better in group B than in group A at 5 months, but there was no substantial difference in response at the 1-year evaluation. Although the study sample was small, our results suggest that the safety of anti-TNF-α therapy is similar in RA patients with and without concomitant HCV infection.
24942602 Meta-analysis of genetic polymorphisms in programmed cell death 1. Associations with rheum 2015 Apr OBJECTIVE: The aim of this study was to determine whether genetic polymorphisms in programmed cell death 1 (PDCD1 or PD1) are associated with susceptibility to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and type 1 diabetes (T1D). METHODS: We conducted a meta-analysis to investigate the association between PDCD1 polymorphisms and RA, AS, and T1D in the overall population and in specific ethnic populations. RESULTS: Sixteen studies, comprising 13,210 patients and 17,073 controls, were conducted for the meta-analysis including 4 studies on RA, 4 on AS, and 8 on T1D. The meta-analysis showed an association between RA and the 2 alleles of the PD1.3 polymorphism in the overall population [odds ratio (OR) 1.183, 95 % confidence interval (95 % CI) 1.005-1.392, p = 0.043]. However, meta-analysis showed no association between RA and the 2 alleles of the PD1.1 and PD1.5 polymorphisms in the overall population. Meta-analysis identified an association between AS and the 2 alleles of the PD1.5 and PD1.9 polymorphisms in the Asian population (OR 1.251, 95 % CI 1.019-1.535, p = 0.033; OR 1.975, 95 % CI 1.286-3.034, p = 0.002, respectively). The meta-analysis revealed a significant association between T1D and the 2 alleles of the PD1.3 polymorphism in the European population (OR 1.098, 95 % CI 1.029-1.171, p = 0.005). The meta-analysis showed an association between the PD1.5 polymorphism and T1D in Asians (OR 1.332, 95 % CI 1.067-1.663, p = 0.011) and between the PD1.9 polymorphism and T1D in the Asian population (OR 1.363, 95 % CI 1.107-1.679, p = 0.004). CONCLUSION: The meta-analysis suggests an association between the PD1.3 polymorphism and RA in the overall population and an association between the PD1.5 and PD1.9 polymorphisms, and AS in the Asian population. Furthermore, the PD1.3 , 5, and 9 polymorphisms were associated with T1D susceptibility in Europeans, or Asians.
26573002 The spectrum of histopathologic findings in cutaneous lesions in patients with Still disea 2015 Dec OBJECTIVES: Still disease is a rare disorder characterized by seronegative arthralgias/arthritis, spiking fever, and either an evanescent salmon-colored rash or persistent papules and plaques. METHODS: We describe the clinical and biopsy findings in 10 patients with the evanescent rash of Still disease. RESULTS: Fourteen biopsy specimens were studied from seven women and three men with a mean age of 44.4 years. The skin lesions were typically erythematous macules, papules, or plaques with a median duration of 5 weeks. All patients had systemic symptoms, including fever and arthralgias. The infiltrate was predominantly lymphocytic in six biopsy specimens, approximately equal lymphocytic and neutrophilic in four biopsy specimens, and predominantly (although never exclusively) neutrophilic in four biopsy specimens. Other findings included focal vacuolar interface changes, neutrophilic eccrine hidradenitis, epidermal neutrophils, dermal mucin, and acanthosis associated with numerous upper epidermal dyskeratotic cells. CONCLUSIONS: It is important to be aware of the broad histologic spectrum that may be encountered in Still disease and to consider Still disease in the differential diagnosis of neutrophil-rich, lymphocyte-rich, and mixed inflammatory dermatoses. While the histologic findings seen in biopsy specimens of the evanescent rash are nonspecific, a distinctive variant also exists characterized by prominent epidermal apoptosis, especially involving the upper layers.
25618317 Medication adherence and attrition to biologic treatment in rheumatoid arthritis patients. 2015 Mar 1 PURPOSE: The objectives of this study were to assess medication adherence rate and attrition rate in first-time adalimumab (ADA) or etanercept (ETA) users in rheumatoid arthritis (RA) patients. This study also identified the risk factors associated with nonadherence and treatment abandonment. METHODS: This was a retrospective study with a 2-year follow-up. A total 2151 adult RA patients (18 years of age and older) who initiated ADA or ETA treatment in the Kaiser Permanente Southern California health plan between 2002 and 2009 were identified. Among those on treatment in the first year, continuous treatment receipt was determined by having at least 1 medication refill in the second year; otherwise treatment was considered as abandoned. Medication adherence was measured through proportion of days covered (PDC) and compared between patients continuously on treatment and those abandoning treatment. Risk factors of nonadherence (PDC <80%) and treatment abandonment were estimated by a multinomial logistic regression model. FINDINGS: Patients who abandoned treatment had significantly lower PDC (37.3%) and lower average number of refills (5.1) than adherers (PDC = 88.8%; average number of refills = 12.4) and nonadherers (PDC = 53.3%; average refills = 8.2). Age, African Americans (odds ratio [OR], 1.49; 95% CI, 1.03-2.17), corticosteroids use (OR, 0.80; 95% CI, 0.63-0.98), and history of physical/occupational therapy (OR = 0.66; 95% CI, 0.46-0.93) were associated with nonadherence, whereas having a comorbidity (OR, 1.24; 95% CI, 1.01-1.57) was associated with treatment abandonment. The difference in PDC between ADA and ETA was no longer statistically significant after excluding the treatment abandonment group. A higher proportion of ADA users abandoned treatment than ETA users (42.9% vs 32.2%). IMPLICATIONS: Taking into account treatment abandonment when measuring medication adherence in ADA and ETA use in RA patients can provide a fair and clinically meaningful view of patients' medication-taking behavior.
25885039 Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility 2015 Mar 18 INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.
26979320 Digital X-ray radiogrammetry and its sensitivity and specificity for the identification of 2017 Mar Digital X-ray radiogrammetry (DXR) is a computer-assisted diagnosis technique for quantifying cortical hand bone mineral density (BMD) as well as the metacarpal index (MCI) in the metacarpal bones from radiographs. The objective was to compare DXR-BMD and DXR-MCI between healthy individuals and patients with rheumatoid arthritis (RA) and verify the sensitivity and specificity of this technique for the identification of cortical hand bone loss as an additional diagnostic approach in RA. 618 patients were enrolled and divided into two groups: those with RA (n = 309) and a healthy control group (n = 309) as a reference database. DXR-BMD and the DXR-MCI were measured by DXR using hand radiographs. The severity of RA was evaluated by the modified Larsen score. Mean values for DXR-BMD and DXR-MCI in RA patients were significantly lower compared to healthy subjects (-20.7 and -21.1 %, respectively). Depending on the severity of RA-related joint damage, DXR-BMD revealed a significant reduction of -28.1 % and DXR-MCI -28.2 %, comparing score 1 and score 5 of the modified Larsen score. Both DXR-BMD and DXR-MCI had a high sensitivity (DXR-BMD 91 %, DXR-MCI 87 %) and a moderate specificity (DXR-BMD 47 %, DXR-MCI 49 %) to identify RA-related cortical hand bone loss. The DXR technique seems to be able to quantify RA-related periarticular bone loss as a characteristic feature in the course of RA. Consequently, periarticular osteoporosis seems to function as a reliable diagnostic approach comparable to erosions and joint space narrowing in the diagnosis of RA and as a surrogate marker for the progression of bone loss in RA.