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ID PMID Title PublicationDate abstract
25187700 Bisphosphonate therapy and osteonecrosis of the jaw complicated with a temporal abscess in 2014 Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction described as the progressive destruction and death of bone tissue of the mandible or maxilla, in the course of bisphosphonate therapy. Orally administered bisphosphonates, widely used for the treatment of osteoporosis, are rarely associated with BRONJ. Instead, the risk greatly increases whether the patient is concomitantly taking steroid and/or immunosuppressant agents. The aims of this paper are to briefly discuss the evidence of the associations between bisphosphonate therapy and BRONJ, and the effects of co-occurring factors such as the presence of rheumatoid arthritis, dental surgery, and concomitant corticosteroid therapy. In particular, we present the case of an elderly woman with BRONJ suffering from rheumatoid arthritis, with a recent dental extraction and with a very unusual complication: a temporal abscess, who was successfully treated.
23962625 A parallel group cohort to determine the measurement properties of an early inflammatory a 2013 Nov OBJECTIVES: To determine the comprehensibility, internal consistency, test-retest reliability and discriminative properties of an early inflammatory arthritis (IA) detection tool. METHODS: Four groups were recruited from outpatient clinics at two tertiary care hospitals: early IA, established IA, non-IA musculoskeletal conditions (MSK) and non-MSK. Participants attended a study visit where they completed the 11-item tool with binary yes/no response options. Comprehensibility was assessed for each tool item on a 5-point Likert scale. For test-retest assessment, the tool was mailed to participants following a 2-week recall washout interval. Two items were randomly selected to test internal consistency. Discriminative properties compared tool item responses with blinded rheumatologist clinical assessments. A previously developed rheumatology triage algorithm was externally validated. RESULTS: A total of 170 participants were enrolled in the study. Comprehensibility approached unity for all tool items. The internal consistency Kuder-Richardson Formula 20 was 0.985 (P < 0.0001). The mean test-retest reliability kappa (S.D.) was 0.81 (0.02). The intraclass correlation coefficient (ICC) (95% CI) for summed yes responses between test and retest phases was 0.94 (0.93, 0.95) and for algorithm scores was 0.97 (0.96, 0.98). Patient responses were significantly associated with the corresponding clinical evaluations (P < 0.0001, respectively). The sum of yes responses and rheumatology triage algorithm scores both differentiated early IA from each of the other three groups (P < 0.004, respectively). The scoring algorithm receiver operating characteristic plot area under the curve (S.E.) was 0.829 (0.003). CONCLUSION: The tool has favourable measurement and discriminative properties. The discriminative properties of the rheumatology triage scoring algorithm were externally validated.
25313147 Clinical characteristics of RA patients with secondary SS and association with joint damag 2015 May OBJECTIVES: Secondary SS (sSS) is a common extra-articular manifestation of RA. There are conflicting data regarding the association of sSS with worse joint damage. This study aims to characterize sSS patients in an RA cohort and study the association between sSS and joint damage. METHODS: We conducted a cross-sectional study of RA patients with ≥1 year of follow-up at a large academic centre. Subjects with co-morbid diseases that can also result in sicca symptoms were excluded from the analysis. Subjects were considered to have sSS if they were reported as having sSS by their rheumatologist at recruitment into the cohort and had the diagnosis confirmed by chart review. The primary outcome was Sharp score using bilateral hand radiographs at recruitment. We constructed a linear regression model to determine the association of sSS status and Sharp score adjusted by age, gender, disease duration and ACPA and RF status. RESULTS: We studied 829 RA subjects, mean age 57 years, 83% female, mean RA duration 13 years, 74% seropositive; 85 subjects (10.3%) had sSS. We observed a female predominance (95.3%), longer mean disease duration (16.9 years) and higher frequency of RF or ACPA positive among patients with sSS and RA. Having sSS at baseline was associated with higher Sharp scores (P = 0.03), independent of age, gender, RA disease duration and seropositive disease. CONCLUSION: In our RA cohort, RA subjects with sSS had worse joint damage, suggesting that sSS is a marker of more aggressive disease.
24071881 Clinical course and outcome of rheumatoid arthritis-related usual interstitial pneumoni 2013 Aug 1 BACKGROUND: Although the prognosis of interstitial pneumonia in connective tissue disorders is better than that of idiopathic pulmonary fibrosis (IPF), the prognosis of rheumatoid arthritis (RA) related usual interstitial pneumonia (UIP) is controversial. OBJECTIVES: To determine prognosis, clinical course and prognostic factors of the patients with RA-UIP and compare them to IPF. DESIGN: Retrospective review of 84 patients with RA-UIP (biopsy-proven: 30) from two tertiary referral centers. RESULTS: The median follow-up period was 33 months. One half of the patients were stable, one third progressed, 17% had acute exacerbation and 6% improved. TLC % predicted was the only significant predictor for the stable group. Among non-AEx patients, 41% was treated due to poor initial lung function or progression of the disease and one half of them improved or had stable lung function. Despite of worse initial lung function, the survival of treated group was similar to untreated group. Age, FVC and change in DLco during 6 months were significant predictors for mortality. The prognosis of RA-UIP was significantly better than that of IPF matched with age, sex, smoking and baseline lung function (median survival, 53 vs. 41 months respectively, p = 0.015). CONCLUSIONS: In spite of variable clinical course of RA-UIP, overall prognosis of RA-UIP was significantly better compared to IPF. Our data supported the treatment of the patients with significant functional impairments or progression.
24584926 Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the A 2014 Apr OBJECTIVE: Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). METHODS: The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported. RESULTS: Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8-44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA. CONCLUSION: These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).
24783914 Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept). 2014 GOAL: To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. RESULTS: During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. CONCLUSION: At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more nonbiologic DMARDS.
24907345 The inhibitory effect of IFN-γ on protease HTRA1 expression in rheumatoid arthritis. 2014 Jul 1 The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated that IFN-γ significantly inhibited the basal and LPS-induced HTRA1 expression in fibroblasts and macrophages, which are two major cells for HTRA1 production in RA. Importantly, the inhibitory effect of IFN-γ on HTRA1 expression was evidenced in collagen-induced arthritis (CIA) mouse models and in human RA synovial cells. In parallel with the enhanced CIA incidence and pathological changes in IFN-γ-deficient mice, HTRA1 expression in the joint tissues was also increased as determined by real-time PCR and Western blots. IFN-γ deficiency increased the incidence of CIA and the pathological severity in mice. Neutralization of HTRA1 by Ab significantly reversed the enhanced CIA frequency and severity in IFN-γ-deficient mice. Mechanistically, IFN-γ negatively controls HTRA1 expression through activation of p38 MAPK/STAT1 pathway. Dual luciferase reporter assay and chromatin immunoprecipitation analysis showed that STAT1 could directly bind to HTRA1 promoter after IFN-γ stimulation. This study offers new insights into the molecular regulation of HTRA1 expression and its role in RA pathogenesis, which may have significant impact on clinical therapy for RA and possibly other HTRA1-related diseases, including osteoarthritis, age-related macular degeneration, and cancer.
24984716 Judging health risk as a function of risk factors and type of illness: Do people weight ri 2016 May We examined the extent to which lay people and health professionals are able to assess occurrence risks for multifactorial diseases. We asked 341 participants to assess the risk of developing lung cancer, coronary artery disease or rheumatoid arthritis in 16 scenarios, each featuring a combination of four factors (family history, daily alcohol intake, daily tobacco consumption and genetic test results). Participants considered all factors. However, they accorded more weight to tobacco and genetic test results. Moreover, it appears that where one of the factors (e.g. the presence of the incriminated gene) exerted a strong influence, the influence of the other factor(s) was correspondingly weaker. The health risk judgements of health professionals were more dependent on the specific disease and were also influenced to a greater degree by genetic information than lay people.
23179138 Anti-inflammatory and antioxidant potential of alginic acid isolated from the marine algae 2013 Jun The present study evaluated the anti-inflammatory and antioxidant potential of alginic acid isolated from brown algae Sargassum wightii in arthritic rats. Arthritis was induced in male Sprague-Dawley rats by intradermal injection of complete Freund's adjuvant into the right hind paw, produce inflammation of the joint tissue. Paw edema volume, enzymes linked to inflammation such as cyclooxygenase, lipoxygenase and myeloperoxidase, and the level of ceruloplasmin, C-reactive protein and rheumatoid factor were evaluated in all the experimental groups. Oxidative stress during inflammation was analyzed by estimating lipid peroxidation and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant, reduced glutathione. Alginic acid treatment (100 mg/kg) in arthritic rats exhibited reduced paw edema volume along with reduced activities of enzymes such as cyclooxygenase, lipoxygenase and myeloperoxidase. Reduction in the level of C-reactive protein, ceruloplasmin and rheumatoid factor were also observed in arthritic rats treated with alginic acid along with reduced lipid peroxidation and enhanced activities of antioxidant enzymes, which suggest the antioxidant potential of the compound. Histopathological analysis of paw tissue showed that alginic acid treatment reduced paw edema and inflammatory infiltration in arthritic rats. Overall results suggest that alginic acid isolated from Sargassum wightii exhibits potent anti-inflammatory and antioxidant activity, and can develop this marine alga as an alternative source for therapy and can be used as a drug candidate for the development of anti-inflammatory agent.
24173963 TNFα blockade for inflammatory rheumatic diseases is associated with a significant gain i 2014 Apr PURPOSE: To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). METHODS: Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed. RESULTS: There was a significant gain in body mass index (p = 0.05) and a tendency for weight (p = 0.07), android fat (p = 0.07), and visceral fat (p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased (p = 0.02) with a parallel weight gain (p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9%; p = 0.003), body mass index (+2.5%; p = 0.004), total fat mass (+11.1%; p = 0.007), and fat in the android region (+18.3%; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3%; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (-15.2%, p = 0.057 and -9.3%, p = 0.067, respectively). Resistin decreased significantly (-22.4%, p = 0.01). CONCLUSIONS: Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments.
23570265 A pharmacokinetic and clinical assessment of tofacitinib for the treatment of rheumatoid a 2013 Jun INTRODUCTION: Rheumatoid arthritis (RA) is a chronic painful and debilitating autoimmune disease. Although the outcome for patients with RA has improved markedly in the past decades, driven largely by the advent of biological disease-modifying antirheumatic drugs (DMARDs) and updated management strategies, adequate disease control cannot be achieved in a substantial proportion of patients. Since RA is a syndrome with different biological subsets, DMARDs, with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Tofacitinib is a novel synthetic DMARD that selectively inhibits Janus kinases (JAKs), particularly JAK1 and JAK3. AREAS COVERED: This review describes the pharmacokinetics of tofacitinib. Furthermore, the article summarizes and comments the drug's efficacy and safety profile in RA patients. The authors furthermore assess data derived from the FDA's RA development program. EXPERT OPINION: Tofacitinib is an oral synthetic DMARD displaying linear pharmacokinetics. Metabolism, primarily mediated by CYP3A4, accounts for 70% of the total clearance of the drug; the remaining 30% are renally excreted. Tofacitinib monotherapy, or in combination with traditional DMARDs, has demonstrated its efficacy while having an acceptable safety profile in RA patients who have responded inadequately to current DMARDs, including TNF antagonists. In view of its undetermined benefit to risk ratio, in the real-world population, tofacitinib should, for now, only be prescribed to selected patients.
23264341 Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus. 2013 Sep 1 OBJECTIVES: Recent data debate the suitability of Helios, an Ikaros family member, as a marker for thymic-derived regulatory T cells (Treg). Nevertheless, Foxp3(+) Helios(+) Treg may be of particular relevance in mediating immune tolerance in chronic autoimmunity, such as systemic lupus erythematosus (SLE), as they possess enhanced suppressive function, compared to Foxp3(+) Helios(-) Treg. METHODS: Multicolour flow cytometry was performed to analyse Foxp3 and Helios expression in peripheral blood CD4 T cells from SLE patients, compared to healthy controls (HC) and systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. Cytokine production, chemokine receptor expression for CXCR3 and CCR4, basal signal transducer and activator of transcription 5 (STAT5)a phosphorylation levels and T-cell receptor (TCR) Vβ repertoire were analysed by flow cytometry, and the methylation status of the Foxp3 locus (Treg-specific demethylated region, TSDR) by real-time PCR. RESULTS: Frequencies of Foxp3(+) Helios(+) Treg, unlike Foxp3(+) Helios(-) T cells, were significantly increased in SLE patients and positively correlated with disease activity, whereas they were unaltered in SSc and RA patients. Compared to HC, Foxp3(+) Helios(+) Treg in SLE predominantly displayed a CD45RA(-)/CD31(-)/FoxP3(low) memory phenotype with increased Ki-67 expression, enhanced basal pSTAT5a levels and a restricted TCR repertoire. Nonetheless, similar to HC, Foxp3(+) Helios(+) Treg in SLE lacked effector cytokine production, possessed a highly demethylated TSDR and expressed comparable levels of CXCR3 and CCR4. CONCLUSIONS: Our data suggest that Helios-expressing Foxp3(+) Treg with functional suppressive capacity and migratory potential into inflamed tissues are expanded in active SLE, presumably through γ-chain signalling cytokines and TCR stimulation, to compensate for autoreactive effector responses.
25448791 Genetic polymorphisms of Foxp3 in patients with rheumatoid arthritis. 2015 Feb OBJECTIVE: The aim of the study was to identify 2 polymorphic variants in the promoter region of the Foxp3 gene and their possible association with susceptibility to and severity of rheumatoid arthritis (RA). The association between genetic factors and pathogenesis suggests that T cells take part in the induction of RA. The CD4+CD25highFoxp3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. METHODS: Patients with RA (n = 274) and healthy individuals (n = 295) were examined for -3279 C/A and -924 A/G Foxp3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. Serum Foxp3 levels in patients with RA and controls were measured with ELISA. RESULTS: Foxp3 -3279 A and -924 G alleles were associated with significantly elevated risk of RA in the population tested (p = 0.003 and p = 0.004, respectively) compared to the wild-type alleles. Overall, -3279 C/A and -924 A/G Foxp3 gene polymorphisms were in indistinct linkage disequilibrium with D' = 0.481 and r(2) = 0.225. From 4 possible haplotypes, frequencies of 2 (AG and CA) showed significant differences between both examined groups (respectively, p < 0.001 and p = 0.007). After appropriate adjustment of Bonferroni correction for multiple testing, the genotype-phenotype analysis showed no significant correlation of the Foxp3 -3279 C/A and -924 A/G polymorphisms with the disease activity, joint damage, laboratory variables, and extraarticular manifestation in patients with RA. Serum Foxp3 level was significantly higher in patients than in controls (p < 0.0001). CONCLUSION: Current findings indicated that the Foxp3 genetic polymorphism and the Foxp3 protein level may be associated with susceptibility to RA in the Polish population.
25022442 Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drug 2015 May OBJECTIVES: To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). PATIENTS AND METHODS: The patients received subcutaneous golimumab 50mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. RESULTS: A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR>5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). CONCLUSION: The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab.
24574212 Brief report: does medication use or disease activity during pregnancy in patients with rh 2014 Mar OBJECTIVE: Prednisone use and active disease are associated with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Either or both of these factors may be inevitable during pregnancy in women with RA, but it is unknown whether they variables influence the BMD of the offspring. This study was undertaken to investigate whether medication use or disease activity during pregnancy in RA patients influences the BMD of their prepubertal offspring. METHODS: Mothers (n = 255) participated in a prospective cohort study of RA and pregnancy, and 108 children of these mothers (ages 5-10 years) were included in this followup study. Information on features known to influence BMD in children, i.e., calcium intake, physical activity, serum 25-hydroxyvitamin D level, sex, height, and weight, was collected. In addition, pre- and postnatal variables known to influence BMD, i.e., gestational age, maternal smoking, birth weight, postnatal rate of growth, and type of feeding, were recorded. Independent variables were prednisone use, sulfasalazine use, and RA disease activity during pregnancy. RESULTS: We found no association of BMD in the children with either prednisone use or RA disease activity during pregnancy, even after correcting for all known associated variables. Sulfasalazine use during pregnancy had a positive effect on the total-body BMD of the offspring (difference in standard deviation score 0.53, P = 0.005). CONCLUSION: Our findings indicate that neither medication use nor high RA disease activity during pregnancy is associated with decreased BMD in offspring at age ∼7 years. The maternal benefit of medication use for RA during pregnancy outweighs the effect on BMD in the offspring.
24476340 MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI 2014 Jan 30 INTRODUCTION: Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors. METHODS: A total of 38 RA patients and 22 controls were enrolled at t = 0 (2009). After 3 years, clinical and MRI data were available in 28 patients and 15 controls. 3T MRI scans were scored for cartilage damage, bone erosion, synovitis and osteitis. A model was developed to predict cartilage damage from baseline parameters. RESULTS: Inter-reader reliability for the Auckland MRI cartilage score (AMRICS) was high for status scores; intraclass correlation coefficient (ICC), 0.90 (0.81 to 0.95) and moderate for change scores (ICC 0.58 (0.24 to 0.77)). AMRICS scores correlated with the Outcome MEasures in Rheumatoid Arthritis Clinical Trials (OMERACT) MRI joint space narrowing (jsn) and X-Ray (XR) jsn scores (r =0.96, P < 0.0001 and 0.80, P < 0.0001, respectively). AMRICS change scores were greater for RA patients than controls (P = 0.06 and P = 0.04 for the two readers). Using linear regression, baseline MRI cartilage, synovitis and osteitis scores predicted the three-year AMRICS (R² = 0.67, 0.37 and 0.39, respectively). A multiple linear regression model predicted the three-year AMRICS (R² = 0.78). Baseline radial osteitis predicted increased cartilage scores at the radiolunate and radioscaphoid joints, P = 0.0001 and 0.0012, respectively and synovitis at radioulnar, radiocarpal and intercarpal-carpometacarpal joints also influenced three-year cartilage scores (P-values of 0.001, 0.04 and 0.01, respectively). CONCLUSIONS: MRI cartilage damage progression is preceded by osteitis and synovitis but is most influenced by pre-existing cartilage damage suggesting primacy of the cartilage damage pathway in certain patients.
24238968 Midterm results of resection arthroplasty for forefoot deformities in patients with rheuma 2014 Jan We investigated the midterm results of resection arthroplasty of all 5 metatarsal heads in patients with rheumatoid arthritis and forefoot deformity and analyzed the factors that affect patient satisfaction levels. Of 64 patients (1 male, 63 females), 107 feet were treated with resection arthroplasty for forefoot deformity at our hospital from January 1992 to December 2005. The mean follow-up period was 5.8 ± 3.1 years, with all patients having at least 1 year of follow-up. Of the 64 patients, 75% were satisfied with the surgery. The mean score for the postoperative Japanese Society for Surgery of the Foot lesser metatarsophalangeal-interphalangeal scale was 75.0 ± 15.8 points. Multivariate logistic regression analysis showed that patient-reported dissatisfaction was significantly associated with the recurrence of hammer toe deformity (odds ratio 2.66, 95% confidence interval 1.07 to 6.97), shortening of the resection arthroplasty space (odds ratio 0.85 for a 1-unit increase, 95% confidence interval 0.74 to 0.96), and the recurrence of hallux valgus (odds ratio 1.04 for a 1-unit increase, 95% confidence interval 1.00 to 1.09) during the postoperative period. From our results, interventions to prevent recurrence of hammer toe deformity, especially in toes with preoperative metatarsophalangeal joint dislocations, have been shown to be important in preventing complications and patient dissatisfaction after resection arthroplasty.
25378596 Borrelia burgdorferi arthritis-associated locus Bbaa1 regulates Lyme arthritis and K/B×N 2014 Dec 15 Localized upregulation of type I IFN was previously implicated in development of Borrelia burgdorferi-induced arthritis in C3H mice, and was remarkable due to its absence in the mildly arthritic C57BL/6 (B6) mice. Independently, forward genetics analysis identified a quantitative trait locus on Chr4, termed B. burgdorferi-associated locus 1 (Bbaa1), that regulates Lyme arthritis severity and includes the 15 type I IFN genes. Involvement of Bbaa1 in arthritis development was confirmed in B6 mice congenic for the C3H allele of Bbaa1 (B6.C3-Bbaa1), which developed more severe Lyme arthritis and K/B×N model of rheumatoid arthritis (RA) than did parental B6 mice. Administration of a type I IFN receptor blocking mAb reduced the severity of both Lyme arthritis and RA in B6.C3-Bbaa1 mice, formally linking genetic elements within Bbaa1 to pathological production of type I IFN. Bone marrow-derived macrophages from Bbaa1 congenic mice implicated this locus as a regulator of type I IFN induction and downstream target gene expression. Bbaa1-mediated regulation of IFN-inducible genes was upstream of IFN receptor-dependent amplification; however, the overall magnitude of the response was dependent on autocrine/paracrine responses to IFN-β. In addition, the Bbaa1 locus modulated the functional phenotype ascribed to bone marrow-derived macrophages: the B6 allele promoted expression of M2 markers, whereas the C3H allele promoted induction of M1 responses. This report identifies a genetic locus physically and functionally linked to type I IFN that contributes to the pathogenesis of both Lyme and RA.
23010850 Acute and long-term effect of infliximab on humoral and echocardiographic parameters in pa 2013 Jan Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.
24720727 Efficacy and safety implications of molecular constructs of biological agents for rheumato 2014 Jul INTRODUCTION: Targeted biologic immunomodulatory therapies have had a major impact in rheumatoid arthritis (RA) treatment, including tumor necrosis factor (TNF)-α inhibition, B-cell depletion, interference in T-cell costimulation and interleukin (IL)-1 and IL-6 inhibition. Along with the recognition of the importance of early, aggressive disease-modifying antirheumatic drugs (DMARDs) grounded in the use of methotrexate, the introduction of biologic DMARDs (bDMARDs) has provided significantly improved outcomes in patients with RA with a goal of true remission, or at least a state of very low disease activity, now possible in many. There are a number of methods to inhibit cytokines, cellular receptors and pathways of signal transduction that have been used thus far and are in development. In some cases, the method of target inhibition and differences in molecular construct has impacted efficacy and/or safety; whereas, in other cases, similar safety and/or efficacy signals across compounds have demonstrated class- or target-related effects. As the development of targeted therapies moves forward, it is increasingly important to understand the role of the target both in RA disease pathogenesis and normal host defense and the mechanisms of target inhibition. AREAS COVERED: This review covers the targets of therapy for biologic agents in rheumatic diseases, their molecular constructs and implications on efficacy and safety, with focus on approved treatments for RA. EXPERT OPINION: Advances in molecular biology have provided a number of different ways to impact pathobiologically relevant pathways and targets in terms of the molecular construct of individual compounds. The use of these agents have provided important mechanistic insights into disease pathogenesis, and in some cases are associated with differences in efficacy and safety among agents even with the same downstream target. As bDMARDs identify promising mechanisms, oral agents that target or specifically regulate downstream pathways are made possible.