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ID PMID Title PublicationDate abstract
21898356 Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid 2012 Jan OBJECTIVE: To conduct a prospective pilot study to determine whether macrophage targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize subclinical synovitis in arthralgia patients who have anti-citrullinated protein antibodies (ACPAs). METHODS: Twenty-nine arthralgia patients who were positive for ACPAs but did not have clinical arthritis were studied. High (spatial)-resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed. For all metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient), tracer uptake was scored semiquantitatively (0-3 scale) by 2 observers who were blinded with regard to the clinical data. Patients were followed up prospectively for 24 months to investigate the development of clinical arthritis. RESULTS: Overall agreement and kappa values for the readings of the 2 observers were, respectively, 97% and 0.91 (95% confidence interval [95% CI] 0.74-1) at the patient level and 99% and 0.81 (95% CI 0.65-0.96) at the joint level. In 4 patients, at least 1 and as many as 5 PET-positive joints (score≥1) were found at baseline. Within 2 years of followup, 9 patients had developed clinical arthritis. This included all 4 patients with positive findings on the 11C-(R)-PK11195 scan, who developed clinical arthritis in the hand/wrist region, as identified on PET scans. Of the 5 remaining arthritis patients with negative findings on PET scans, 2 developed arthritis in the hand joints and 3 developed arthritis at locations outside the field of view of the PET scanner. CONCLUSION: Subclinical arthritis in ACPA-positive arthralgia patients could be visualized by 11C-(R)-PK11195 PET scanning and was associated with development of arthritis within 2 years of followup. This indicates that 11C-(R)-PK11195 PET may be useful in determining arthritis activity in the preclinical phase of RA.
21984766 Intrinsic danger: activation of Toll-like receptors in rheumatoid arthritis. 2012 Jan RA is a debilitating disorder that manifests as chronic localized synovial and systemic inflammation leading to progressive joint destruction. Recent advances in the molecular basis of RA highlight the role of both the innate and adaptive immune system in disease pathogenesis. Specifically, data obtained from in vivo animal models and ex vivo human tissue explants models has confirmed the central role of Toll-like receptors (TLRs) in RA. TLRs are pattern recognition receptors (PRRs) that constitute one of the primary host defence mechanisms against infectious and non-infectious insult. This receptor family is activated by pathogen-associated molecular patterns (PAMPs) and by damage-associated molecular patterns (DAMPs). DAMPs are host-encoded proteins released during tissue injury and cell death that activate TLRs during sterile inflammation. DAMPs are also proposed to drive aberrant stimulation of TLRs in the RA joint resulting in increased expression of cytokines, chemokines and proteases, perpetuating a vicious inflammatory cycle that constitutes the hallmark chronic inflammation of RA. In this review, we discuss the signalling mechanisms of TLRs, the central function of TLRs in the pathogenesis of RA, the role of endogenous danger signals in driving TLR activation within the context of RA and the current preclinical and clinical strategies available to date in therapeutic targeting of TLRs in RA.
21735706 [Biological role and functional characteristics of calcitonin in human and animal organism 2011 Apr In the review the literary data on the subject of biological role and functional characteristics of calcitonin in human and animal organisms are demonstrated. The own results concerning the study of local exposure of calcitonin of salmon (preparation "Miacalcic") on the development of inflammatory destructive processes in articular structures of the affected knee joints in rabbits with experimental rheumatoid arthritis are briefly designated.
21571734 Association of circulating adiponectin levels with progression of radiographic joint destr 2011 Sep BACKGROUND: Adipokines have inflammatory and immunomodulatory properties that may contribute to erosive joint damage. The association of serum adipokine levels with progression of radiographic joint damage in patients with rheumatoid arthritis (RA) was prospectively explored. METHODS: Patients with RA underwent serum adipokine assessment (adiponectin, resistin, leptin) at three timepoints and hand/feet x-rays, scored using the Sharp-van der Heijde Score (SHS), at baseline and the third study visit, separated by an average of 39±4 months. The associations of baseline and average adipokine levels with change in SHS were explored, adjusting for pertinent confounders. RESULTS: Of the 152 patients studied, 85 (56%) showed an increase in SHS (defined as >0 SHS units). Among the adipokines studied, only adiponectin was significantly associated with radiographic progression, with average adiponectin levels more strongly associated than baseline levels. After adjusting for average C reactive protein and baseline SHS, patients in the highest quartile of average adiponectin had a SHS progression rate more than double the lowest quartile (1.00 vs 0.48 units/year; p=0.008). Similarly, those in the highest quartile of adiponectin had a more than fivefold greater odds of any radiographic progression compared with the lowest quartile (OR 5.75; p=0.002). The magnitude of the association of average adiponectin levels with radiographic progression was greater in women, those with body mass index <30 kg/m(2) and those receiving baseline biological disease-modifying antirheumatic drugs. CONCLUSIONS: These prospective data provide evidence of temporality and dose-response in the relationship between circulating adiponectin and erosive joint destruction in RA, and highlight subgroups of patients at highest risk for adiponectin-associated radiographic progression.
20980282 No overall progression and occasional repair of erosions despite persistent inflammation i 2011 Feb AIM: To monitor joint inflammation and destruction in rheumatoid arthritis (RA) patients receiving adalimumab/methotrexate combination therapy using MRI and ultrasonography. To assess the predictive value of MRI and ultrasonography for erosive progression on CT and compare MRI/ultrasonography/radiography for erosion detection/monitoring. METHODS: Fifty-two erosive biological-naive RA patients were followed with repeated MRI/ultrasonography/radiography (0/6/12 months) and clinical/biochemical assessments during adalimumab/methotrexate combination therapy. RESULTS: No overall erosion progression or repair was observed at 6 or 12 months (Wilcoxon; p > 0.05), but erosion progressors and regressors were observed using the smallest detectable change cut-off. Scores of MRI synovitis, grey-scale synovitis (GSS) and power Doppler ultrasonography decreased after 6 and 12 months (p < 0.05), as did DAS28, HAQ and tender and swollen joint counts (p < 0.001). Patients with progression on CT had higher baseline MRI bone oedema scores. The RR for CT progression in bones with versus without baseline MRI bone oedema was 3.8 (95% CI 1.5 to 9.3) and time-integrated MRI bone oedema, power Doppler and GSS scores were higher in bones/joints with CT progression (Mann-Whitney; p < 0.05). With CT as the reference method, sensitivities/specificities for erosion in metacarpophalangeal joints were 68%/92%, 44%/95% and 26%/98% for MRI, ultrasonography and radiography, respectively. Median intraobserver correlation coefficient was 0.95 (range 0.44-0.99). CONCLUSION: During adalimumab/methotrexate combination therapy, no overall erosive progression or repair occurred, whereas repair of individual erosions was documented on MRI, and MRI and ultrasonography synovitis decreased. Inflammation on MRI and ultrasonography, especially MRI bone oedema, was predictive for erosive progression on CT, at bone/joint level and MRI bone oedema also at patient level.
22093579 Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standa 2011 Nov 17 BACKGROUND: This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA). METHODS: Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events. RESULTS: A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated. CONCLUSIONS: This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA. TRIAL REGISTRATION: NCT00649545.
21368320 Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patie 2011 May In this study, we investigated the hypothesis that regulatory T cells (T(reg)) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T(reg) numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T(reg) were determined in vitro. Our data revealed that the suppressive function of T(reg) from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T(reg) numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T(reg) from primary T cells and enhanced preexisting T(reg) function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T(reg) by AT. In conclusion, AT significantly increased T(reg) numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.
21240500 Association between clinical parameters and amyloid-positive area in gastroduodenal biopsy 2012 Apr Our study was aimed to clarify an association between gastrointestinal (GI) amyloid-positive area and various kinds of factors including renal function in reactive amyloidosis associated with rheumatoid arthritis (RA). Twenty-five patients with an established diagnosis of reactive AA amyloidosis participated in the study between January 1989 and December 2009. Each patient satisfied the 1987 American Rheumatism Association criteria for RA. All patients showed amyloid deposits in both of GI and renal tissues. The average amyloid-deposited area was 2.2% in renal tissues and 3.7% in GI tissues although the difference was not statistically significant. Twenty-two patients out of 25 patients showed less than 5% of amyloidosis in renal tissues and nineteen patients showed 5% of amyloidosis in GI tissues. In 5 out of a total of 25 cases, the amyloid-deposited area in GI tissues was lesser than that in renal tissues. Mesangial proliferative glomerulonephritis, thin basement membrane disease (TBMD) and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, renal and GI tissues of % amyloid-positive areas were transformed to common logarithmic values (Log(10)%amyloid), since the histograms showed log-normal distribution. Clinical data were assessed by patient record at the time of GI biopsy. The correlation between Log(10)%GI-amyloid and age, creatinine (Cr), creatinine clearance (Ccr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR) were not significantly associated with Log(10)%GI-amyloid in crude correlation analyses and also in sex- and age-adjusted linear regression analyses. Although GI biopsy was not correlated with clinical factors, GI amyloid-positive areas were larger than renal amyloid-positive areas. Endoscopic screening of the upper GI tract is common in Japan, and amyloid-deposited area in GI tissues was sufficient to use for the diagnosis of amyloidosis compared with renal tissues in terms of convenience and sensitivity.
21131254 Cardiac autonomic function in patients with rheumatoid arthritis: heart rate turbulence an 2011 Feb OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic disease. The risk of cardiovascular morbidity and mortality is high in patients with RA. Heart rate turbulence (HRT) expresses ventriculophasic sinus arrhythmia and has been considered to reflect cardiac autonomic activity. It has been shown that HRT is an independent and powerful predictor of mortality. The aim of this study is to determine if HRT changes in patients with RA in comparison with the healthy controls. METHODS: The study was performed as a cross-sectional study. Twenty-six patients with RA (mean age 56 ± 10 years, 18 women) and 26 healthy controls (mean age 55 ± 9 years, 18 women) were enrolled in this study. All participants underwent 24 hours Holter electrocardiogram monitoring. HRT measurements, turbulence onset (TO) and turbulence slope (TS), were calculated in patients and healthy controls that have at least one ventricular premature complex (VPC) in their Holter recordings. TO is a measure of the early sinus acceleration and TS is the measure of the rate of sinus deceleration that follows the sinus acceleration after a VPC. Mann-Whitney U test was used for comparison of continuous variables and the Chi-square test for comparison of categorical variables. RESULTS: There were no statistically significant differences in TO and TS between the RA and control groups (TO: -2.2 ± 3.1% vs -2.8 ± 2.5%, p=0.25; TS: 11.5 ± 9.7 ms/RR vs 15.5 ± 10.9 ms/RR, p=0.10). CONCLUSION: HRT parameters, which determine the autonomic dysfunction, did not seem to be altered in patients with RA.
22984272 Infliximab is associated with improvement in arterial stiffness in patients with early rhe 2012 Dec OBJECTIVE: To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. RESULTS: At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (-0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient's global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). CONCLUSION: MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.
22139688 Designing micro- and nano-particles for treating rheumatoid arthritis. 2011 Nov Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease that can cause disability and have a negative socioeconomic impact. Despite significant advances in therapeutic options, limitations on the routes of administration and the requirement for frequent and long-term dosing often lead to systemic adverse effects and patient non-compliance. Micro and nanoparticle systems that selectively deliver drugs to inflamed synovium have the potential to improve drug efficacy while leaving extrasynovial tissues unaffected. This review summarizes key design parameters of RA-targeted drug carriers and discusses design considerations for improving RA therapies.
23193984 Raised circulating tenascin-C in rheumatoid arthritis. 2012 Nov 29 INTRODUCTION: The aim of this study was to examine whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TNC) are elevated in musculoskeletal disorders including rheumatoid arthritis (RA) and to assess in RA whether levels are related to clinical disease status and/or patient response to treatment. METHODS: TNC in serum or plasma was quantified by ELISA. Samples from 4 cohorts of RA patients were examined and compared to normal human subjects and to patients with other inflammatory diseases. RESULTS: Circulating TNC levels were significantly raised in patients with RA, as well as patients with systemic lupus erythematosus, idiopathic inflammatory myositis, psoriatic arthritis and ankylosing spondylitis, whilst patients with Sjogren's syndrome displayed levels similar to healthy controls. The highest levels of TNC were observed in RA patients with late stage disease. In early disease TNC levels correlated positively with ultrasound determined erosion scores. Treatment of early RA patients with infliximab plus methotrexate (MTX) resulted in a transient decrease in circulating TNC over the first year of therapy. In contrast, TNC levels increased over time in RA patients receiving MTX alone. In patients treated with infliximab plus MTX, baseline TNC levels significantly correlated with tender joint counts (TJC) at 18 and 54 weeks after initiation of infliximab therapy. CONCLUSIONS: Raised circulating TNC levels are detected in specific inflammatory diseases. Levels are especially high in RA where they may act as a biomarker of bone erosion and a predictor of the effect of infliximab on RA patient joint pain.
23263548 The effects of fenofibrate on inflammation and cardiovascular markers in patients with act 2013 Dec Peroxisome proliferator-activated receptors α (PPARα) agonists, or fibrates, are used in the treatment for dyslipidemia. Experimental data suggest that fibrates have anti-inflammatory properties, and PPARα is essential for the differentiation of endothelial progenitor cells (EPC) which diminished pool in rheumatoid arthritis (RA) contributes to accelerated atherosclerosis. The data on fibrates' effects in patients with RA are limited. The aim of this study was to investigate changes in disease activity, inflammatory markers, lipid profile, and circulating EPC in active RA patients treated with fenofibrate. Twenty-seven patients with active RA taking traditional disease-modifying antirheumatic drugs (DMARDs) were prescribed fenofibrate (145 mg/day) for 3 months. All patients received background traditional DMARDs in stable doses. The outcomes measured were clinical disease activity variables, circulating cytokines, adipokines, lipids, and EPC. Twenty-five patients completed the study. At the end of treatment, there was a significant reduction in DAS28, all individual DAS28 components except tender joint count, the duration of morning stiffness, and in the patient's assessment of disease activity. Fifteen (60 %) patients achieved good/moderate EULAR response, while 10 (40 %) patients satisfied ACR20 response criteria. Treatment with fenofibrate resulted in significant decrease in CRP and IL-6 concentrations and improvement in lipid profile. There was no change in the concentrations of circulating EPC. In conclusion, fenofibrate treatment is associated with reduced inflammation and improved lipid profile in RA patients. Large randomized controlled studies are needed to confirm these results and to define the role of fibrates in the treatment for RA.
22019503 Association of polymorphisms in pre-miRNA with inflammatory biomarkers in rheumatoid arthr 2012 Jan The aim of this study was to detect the association between 2 single nucleotide polymorphisms (SNPs), rs2910164 G>C and rs3746444 T>C, in pre-miRNA (hsa-mir-146a and hsa-mir-499) and the chronic inflammation in the Chinese Han population with rheumatoid arthritis (RA). Two hundred sixty-two Han Chinese patients with RA were recruited in this study. The SNPs were genotyped by polymerase chain reaction restriction fragment length polymorphism. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the plasma concentrations of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1) were measured. There was a significant difference in the levels of CRP and ESR among different genotypes in rs3746444 (p = 0.031 and p = 0.047, respectively). The heterozygote CT had significantly higher levels of CRP and ESR compared with homozygotes CC and TT. No significant association was observed between the SNP rs2910164 and the levels of CRP, ESR, IL-6, TNF-α, and TGF-β1 (all p > 0.05). The results of this study provided the first evidence that the SNP rs3746444 in pre-miR-499 could affect the inflammatory reaction in patients with RA. The findings were significant and might contribute to the clinical assessment of inflammatory activity, which in turn may influence therapeutic decision making.
21771754 Remission of proteinuria and preservation of renal function in patients with renal AA amyl 2012 Feb BACKGROUND: Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. METHODS: A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. RESULTS: Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. CONCLUSION: Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.
21532235 Rheumatoid arthritis following a treatment with IFN-alpha/ribavirin against HCV infection. 2011 We report a 48-year-old man who developed rheumatoid arthritis (RA) after a successful treatment with peg-IFN-alpha plus ribavirin for chronic hepatitis C virus (HCV) infection. He had a history of smoking and a single copy of the HLA-DRB1 shared epitope (SE). In a retrospective analysis, he exhibited the anti-CCP antibodies before the start of IFN plus ribavirin treatment. However, the titers of anti-CCP antibodies and BAFF levels were elevated by the IFN plus ribavirin therapy. These observations suggest that IFN plus ribavirin therapy may work as a "trigger" for RA in genetically and environmentally predisposed individuals by affecting the cytokine network.
21629190 A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheum 2011 Jun BACKGROUND: To examine the effect of probiotics as adjunctive therapy for the treatment of rheumatoid arthritis (RA). A sample size of 30 subjects was calculated to determine a moderate effect. MATERIAL/METHODS: A three month double-blind, placebo-controlled study was performed using probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 capsules administered orally. Inclusion criteria required at least 4 swollen and 4 tender joints and stable medications with no steroids for at least 1 month prior to and during the study. Twenty-nine patients with RA were randomized to treatment. ACR20 responses, serum cytokine levels and safety parameters were assessed. RESULTS: Fifteen patients were randomized to the probiotic group, and 14 to placebo. Three subjects in the probiotic (20%) and one in the placebo group (7%) achieved an ACR20 response (p= 0.33). There was no statistically significant difference between individual components of the ACR20 criteria. Changes in cytokines favored placebo over probiotic. There was a significant improvement in the Health Assessment Questionnaire (HAQ) score in the probiotic group from visit 1 to visit 3 (p=0.02) but no between-group differences. CONCLUSIONS: Due to inclusion criteria, patients selected for the study had stable RA with chronic synovitis, and thus it may have been difficult for an adjunctive therapy to demonstrate improvement within 3 months. Although probiotics did not clinically improve RA as measured by the ACR20, it is interesting that there was functional improvement seen within the probiotic group compared to placebo.
23078814 Payers' views on treating-to-target in rheumatoid arthritis: an English perspective. 2012 Jul OBJECTIVES: Delivering treat-to-target strategies in rheumatoid arthritis (RA) involves commitments from both providers and payers for healthcare. We have summarised the perspectives of payers from England, where the National Health Service (NHS) provides universal care that is without cost for patients. METHODS: We reviewed the literature - including that from the NHS and National Institute for Health and Clinical Excellence (NICE) - concerning payers views on the clinical effectiveness and cost-effectiveness of treat-to-target strategies for RA. RESULTS: Commissioners pay for government-funded English healthcare and providers (divided between General Practitioners (GPs) and Hospital Consultants) and deliver it according to NICE guidance. Treat-to-target using intensive disease-modifying drug (DMARD) combinations with glucocorticoids are recommended for early active RA. Treatment tapering is recommended when disease control is achieved. Some aspects of treat-to-target are recommended in established RA, including the early management of flares and the use of biologics in persistently active RA that is non-responsive to DMARDs. However, treat-to-target is not widely recommended in established RA, mainly because the evidence base is incomplete. English healthcare is moving towards quality care becoming the main driver and is adopting 'integrated care' involving both GPs and consultants for most long-term disorders; RA is likely to be included within these approaches, which are unlikely to focus specifically on treat-to-target. CONCLUSIONS: Payers strongly support treat-to-target in early RA. In established disease there is limited enthusiasm; without stronger evidence for efficacy and cost-effectiveness this is unlikely to change.
22122009 Therapeutic use of vitamin D and its analogues in autoimmunity. 2012 Jan In recent years, there has been great interest in the role of vitamin D in a number of diverse human diseases including autoimmunity, allergy, infection, cardiovascular disease, chronic lung disease, transplantation and cancer. Vitamin D is best known for its role in calcium metabolism; however it also has potent immunomodulatory effects. Epidemiological studies suggest that vitamin D deficiency may be a significant risk factor for many diseases. Furthermore, there is accumulating evidence from experimental studies that vitamin D has anti-inflammatory effects. Recent studies have indicated that a surprisingly high proportion of people are vitamin D deficient, suggesting that vitamin D supplementation may be of benefit to human health. This review will focus on the role of vitamin D in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and diabetes. We will review the epidemiological and experimental evidence for the protective effects of vitamin D in autoimmunity, as well as the preliminary vitamin D intervention studies and the most recent patented vitamin D analogues.
23171360 Minocycline-associated rimmed vacuolar myopathy in a patient with rheumatoid arthritis. 2012 Nov 21 BACKGROUND: The autophagic vacuolar myopathies (AVM) are a group of inherited myopathies defined by the presence of autophagic vacuoles in pathological muscle specimens. AVM can be categorized into three groups: acid maltase deficiency, myopathies characterized by autophagic vacuoles with unique sarcolemmal features, and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions are still being elucidated, some drugs (e.g., chloroquine, its analog, hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA). Here, we describe the first case of minocycline-associated AVM with rimmed vacuole formation. CASE PRESENTATION: A 75-year-old woman suffering from RA has been continuously treated with minocycline (200 mg/day) for the past 7 years. During this time, she developed a myopathy that predominantly affected her lower limbs. Histological studies of biopsied muscle revealed scattered atrophic myofibers with rimmed vacuoles that contained pigment granules. Histochemical staining revealed that the pigment comprised both iron and melanin, which is consistent with type II minocycline-induced cutaneous pigmentation. Under electron microscopy, autophagic vacuoles were consistently observed in association with numerous collections of pigment granules. CONCLUSIONS: This is the first report of minocycline-induced pigmentation in skeletal muscle. The strong association between autophagic vacuoles and the accumulation of minocycline-induced pigments suggest that long-term minocycline treatment induced pigment accumulation, leading to elevation of autophagic activity and RVM. It might also be possible that minocycline directly activated autophagy, as the observed pigments are known to form complexes containing minocycline and/or its metabolites. As long-term minocycline treatment is expected to be used more widely in the future, we must draw attention to this adverse effect.