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ID PMID Title PublicationDate abstract
18815004 Illness perceptions in patients with fibromyalgia. 2009 Jan OBJECTIVE: Former studies in chronic diseases showed the importance of patients' beliefs and perceptions. The Revised Illness Perception Questionnaire was developed to assess these illness perceptions. Our goal was to investigate psychometric properties of the IPQ-R for Fibromyalgia Dutch language version (IPQ-R FM-Dlv) and to describe illness perceptions of participants with FM. METHODS: 196 patients completed the IPQ-R FM-Dlv. Internal consistency, domain structure and inter domain correlations were calculated and compared to the IPQ-R English language version. Scores were compared with chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), and coronary heart disease (CHD). RESULTS: Most psychometric properties were comparable to those of the original IPQ-R. Participants showed a lack of understanding of their illness, expected their FM to be chronic and to have a lot of negative consequences on functioning. In 17 out of 24 domains significant differences were found between FM and CFS, RA, and CHD patients. CONCLUSION: The IPQ-R FM-Dlv showed acceptable psychometric properties, although some aspects need closer examination. Illness perceptions of FM patients on the Dutch questionnaire were non-comparable to CFS, RA, and CHD patients on the English questionnaire. PRACTICE IMPLICATIONS: The IPQ-R FM-Dlv can be used to assess illness perceptions of Dutch FM patients.
19777949 [Radiosynovectomy of the knee--experience thereof]. 2009 May The aim of the study was the evaluation of 90Y radiosynovectomy performed in chronic exudative knee synovitis. The analyzed material comprised 81 90Y injections made between 2004 and 2008. The circumference of a knee, the volume of removed exudate, the knee mobility, the presence of pain, the temperature of a knee and the presence of floating patella (exudate) were evaluated. The percentage of pain-free patients increased from 12% to 50% after 1 year; an additional 10% of patients reported pain relief. The patient percentage with an increased knee temperature fell from 42% to 31% and the patients percentage with exudates decreased from 76% to 27. No improvement was found with respect to knee circumference. The knee mobility improvement (the patients percentage with full mobility) increased from 25% to 59% one month after the treatment) and exudate volume reduction was found only in the subgroup of patients suffering from pigmented villonodular synovitis. The obtained results permit the conclusion that 90Y radiosynovectomy for chronic exudative knee synovitis is an effective treatment modality; it relieves pain and reduces the patients percentage with exudate and increased knee temperature, and in the subgroup of patients suffering from the pigmented villonodular synovitis improves the knee mobility and reduces the volume of evacuated exudate.
20937671 Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate 2011 Jan OBJECTIVES: Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. METHODS: In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. RESULTS: 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p<0.0001); rituximab 2×500 mg + MTX improved clinical outcomes (ACR50 59% vs 42%; p<0.0001) compared with MTX alone but did not significantly reduce the progression of joint damage. Safety outcomes were similar between treatment groups. CONCLUSIONS: Treatment with rituximab 2×1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA. ClinicalTrials.gov identifier NCT00299104.
19949830 DNA methylation and not allelic variation regulates STAT6 expression in human T cells. 2010 Sep STAT6 transcription factor, which has been implicated in commitment to Th2, is known to be activated by IL-4 and IL-13. Accordingly, STAT6 is primarily responsible for the transcriptional effects of IL-4 and IL-13. STAT6-deficient mice are known to have defective IL-4-mediated functions, such as B cell proliferation, Th2 cell development and IgE secretion; therefore, they primarily contain the Th1 phenotype. However, the mechanism responsible for regulation of STAT6 expression transcriptionally and post-transcriptionally has yet to be elucidated. Here, we characterized the human STAT6 promoter gene and found that the transcriptional regulatory elements CCAAT and ATF were important for the STAT6 promoter activity. Direct sequencing analysis revealed that the 13 GT repeat allelic variation in noncoding exon 1 of the STAT6 gene appeared more frequently in 91 patients with asthma or rheumatoid arthritis than the 15 GT repeat variation, which is the dominant phenotype in healthy controls. However, it appears that this allelic variation did not affect the STAT6 transcriptional activity. Interestingly, treatment with a DNA methyltransferase inhibitor markedly increased the expression of STAT6 mRNA and protein in human primary T cells. In contrast, IFN-gamma treatment significantly repressed the STAT6 transcriptional activity. Therefore, the present study provides insight into the molecular basis of STAT6 expression, and in particular, demonstrates that STAT6 expression is associated with DNA hypermethylation rather than promoter polymorphisms or allelic variations.
20552246 Etanercept response in patients with rheumatoid arthritis after secondary loss of efficacy 2010 Dec This study was carried out to determine the effectiveness of half-dose administration of etanercept in patients with rheumatoid arthritis (RA) who exhibited secondary loss of efficacy of infliximab. Seventeen patients were administered 25 mg of etanercept once weekly for at least 1 year after secondary loss of efficacy of infliximab. The mean duration of treatment with infliximab was 32.5 ± 1.3 months. The patient cohort consisted of 3 males and 14 females, with a mean age of 56.3 ± 11.4 years and mean weight of 57.2 ± 10.9 kg. The mean duration of RA was 16.2 ± 10.9 years. The mean Disease Activity Score 28 was decreased significantly, from 5.8 at the initiation of infliximab therapy to 3.6 at the end of observation. There were no withdrawals due to adverse reactions during the study period, although in 2 subjects the agent was changed to tocilizumab due to lack of effect, one after 18 months and the other after 36 months, and 1 subject withdrew after 18 months for financial reasons. A good response can be expected to a half dose of etanercept in patients with secondary loss of efficacy of infliximab. Reduction of the patient's cost burden also makes this a superior treatment.
19846884 Novel role of Pin1 induction in type II collagen-mediated rheumatoid arthritis. 2009 Nov 15 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints and subsequent destruction of cartilage and bone. Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological roles in several diseases, including cancer and neurodegeneration. We found that both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary cultured human chondrocytes showed increased basal expression of proinflammatory proteins (COX-2, inducible NO synthase, TNF-alpha, and IL-1beta). Site-directed mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was coordinately regulated by NF-kappaB, CREB, and C/EBP. Gel shift, reporter gene, and Western blot analyses confirmed that NF-kappaB, CREB, and C/EBP were consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and COX-2 expression in the ankle tissues. Moreover, juglone dose dependently decreased the basal COX-2 expression in primary cultured chondrocytes from RA patients. These results demonstrate that Pin1 induction during RA progress stimulates proinflammatory protein expression by activating NF-kappaB, CREB, and C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.
19332630 Postmarketing surveillance of the safety and effectiveness of etanercept in Japan. 2009 May OBJECTIVE: Postmarketing surveillance (PMS) was conducted evaluating safety and effectiveness of etanercept (ETN; Enbrel) in Japan, following all patients with rheumatoid arthritis (RA) during the conditional approval period of ETN. METHODS: Registration of patients from 1,334 medical sites was conducted between March 2005 and April 2007. Patients were followed for 24 weeks; data regarding patients' background, safety, and effectiveness was recorded centrally. Adverse events (AE) and adverse drug reactions (ADR) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was measured using the Disease Activity Score 28 (DAS28). RESULTS: Of 14,369 patients registered, data collection and evaluation for 7,091 patients by March 2006 is reported. At least 1 AE was observed for 2,173 patients (30.6%); 60% of AE occurred within 8 weeks of starting ETN. Most frequent AE were injection site reaction (n = 377, 5.3%) and rash (n = 228, 3.2%). Serious AE occurred in 403 patients (5.7%); most frequent were pneumonia (n = 59, 0.8%) and interstitial lung disease (n = 42, 0.6%). Pneumonia was the most common specifically important ADR (n = 102, 1.4%). Mean baseline DAS28 was 6.0, which reduced to 4.4 within 4 weeks, and to 3.9 within 24 weeks. The proportion of patients having good or moderate EULAR response measured by DAS28 was 84.1% at Week 24. Effectiveness rates were more favorable in patients concomitantly using methotrexate. Good or moderate EULAR response rate among patients switched from infliximab was 84.9%. CONCLUSION: This extensive observational trial, including all patients with RA in Japan taking ETN, found ETN to be both effective and well tolerated by Japanese patients with RA. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00503503.
20149310 Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and inflamma 2009 Nov OBJECTIVES: Despite the important role of the transcription factor HIF-1alpha in angiogenesis and inflammation, only a few studies on HIF-1alpha expression have been performed in RA patients. The aim of the present study was to identify the layer in synovial tissue of RA patients where HIF1a is expressed and to find out whether HIF-1alpha expression is related to both angiogenesis and inflammation in synovium from RA patients. METHODS: A reproducible staining method for HIF-1alpha was developed. HIF-1alpha -positive cells were quantified in synovial tissue from patients with RA. As control we used synovial tissue from patients with osteoarthritis (OA). The number of HIF-1alpha-positive cells was compared with the number of blood vessels present and was correlated with the amount of inflammation. The amount of inflammation was determined by counting inflammatory cells, by estimating the proliferation marker Ki67 in inflamed tissue, and by using a recently published synovitis score which gives an accurate estimate of the amount of inflammation present. RESULTS: HIF-1alpha was expressed weakly in the lining layer and strongly in the sublining layer in RA synovial tissue. In contrast, HIF-1alpha was only weakly expressed in OA synovial tissue. The number of HIF-1alpha -positive cells correlated strongly with the number of blood vessels in RA synovial tissue and with inflammatory endothelial cell infiltration (blood vessels), cell proliferation (Ki67) and the synovitis score. CONCLUSIONS: HIF-1alpha expression is strongest in the sub-lining layer of RA synovium and is related to both angiogenesis and inflammation in synovium from RA patients. These results thus suggest that HIF-1alpha could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation.
20607810 Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of 2011 Jan Quercetin had been shown to be effective in the management of arthritis. However, bioavailability of quercetin is a concern for such treatment. This work aims at the development of intra-articular drug delivery system by controlled release of quercetin (loaded in microspheres) for the management of rheumatoid arthritis. Polycaprolactone has been used for the preparation of microspheres (with quercetin) using the solvent evaporation method. The physio-chemical characterisation of polycaprolactone-loaded quercetin microspheres was carried out to obtain information about particle size distribution, drug loading efficiency, morphology, thermal properties, polymorphism and release trends in phosphate-buffered saline at pH 7.4 and 37°C. Quercetin-loaded polycaprolactone microspheres were found to be biocompatible as evidenced from in vitro and in vivo studies using a rabbit synovial cells and Wistar rats, respectively. Quercetin release from microspheres of selected formulations showed biphasic nature due to initial burst effect followed by a controlled release. These results suggest that optimised quercetin-loaded polycaprolactone microspheres may be the viable strategy for controlled release of quercetin in the joint cavity for more than 30 days by intra-articular injection to treat rheumatoid arthritis.
18828180 Molecular studies of rheumatoid factor using pseudobioaffinity membrane chromatography. 2009 Mar Using pseudobioaffinity ligand L-histidine immobilized to poly(ethylene vinyl alcohol) hollow fiber membrane is an interesting approach for the purification of total IgG and its subclasses from untreated serum in a single step. Gentle adsorption and elution conditions of this chromatography system allow efficient recovery of the protein in its native form. This approach was employed for the recovery and molecular study of rheumatoid factor (RF), an anti-IgG autoantibody (AAb) that form immune complexes with autologous IgG Abs in the sera. The purity of the recovered molecule was analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), revealed a 150-kDa IgG band and an additional approximately 300 kDa band which may be RF bound IgG complex. Since RF is an AAb, the purified protein was studied for its catalytic functions like peptide, DNA, and RNA hydrolyzing activities. The substrate Pro-Phe-Arg-4-methyl-coumaryl-7-amide (PFR-MCA) hydrolyzing activity by total IgG from different patient sera was found to be greater than healthy controls. In an effort to identify the subclass specificity for the proteolytic function, the pre-purified total IgG fractions from rheumatoid arthritis (RA) sera were subjected to rechromatography using a discriminating buffer. In this experiment, the activity was found in the non-retained fractions suggesting IgG2 specificity for the catalytic function. A comparative study between different catalytic functions was performed for IgG separated from individual patient.
21119171 Simultaneous bilateral versus unilateral total ankle replacement: a patient-based comparis 2010 Dec The aim of this study was to compare the outcome of bilateral sequential total ankle replacement (TAR) with that of unilateral TAR. We reviewed 23 patients who had undergone sequential bilateral TAR under a single anaesthetic and 46 matched patients with a unilateral TAR. There were no significant pre-operative differences between the two groups in terms of age, gender, body mass index, American Society of Anaesthesiologists classification and aetiology of the osteoarthritis of the ankle. Clinical and radiological follow-up was carried out at four months, one and two years. After four months, patients with simultaneous bilateral TAR reported a significantly higher mean pain score than those with a unilateral TAR. The mean American Orthopaedic Foot and Ankle Society hindfoot score and short-form 36 physical component summary score were better in the unilateral group. However, this difference disappeared at the one-and two-year follow-ups. Bilateral sequential TAR under one anaesthetic can be offered to patients with bilateral severe ankle osteoarthritis. However, they should be informed of the long recovery period.
20112284 TLR4-dependent induction of vascular adhesion molecule-1 in rheumatoid arthritis synovial 2010 May Lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated signaling pathways have caught the attention of strategies designed for rheumatoid arthritis (RA). In this study, we identified that cPLA(2)alpha acted as a modulator of LPS-induced VCAM-1 expression and THP-1 (human acute monocytic leukemia cell line) adherence. Treatment of RA synovial fibroblasts (RASFs) with LPS, a TLR4 agonist, promoted the VCAM-1 expression and THP-1 adherence which were decreased by pretreatment with a selective cytosolic phospholipase A(2) (cPLA(2)) inhibitor (AACOCF(3)), implying the involvement of cPLA(2)alpha in these responses. This notion was further confirmed by knockdown of cPLA(2)alpha expression by transfection with cPLA(2)alpha small interfering RNA (siRNA) leading to a decrease in VCAM-1 expression and THP-1 adherence induced by LPS. Subsequently, the LPS-stimulated cPLA(2)alpha phosphorylation was attenuated by pretreatment with a MEK1/2 inhibitor (U0126), suggesting that LPS-stimulated cPLA(2)alpha phosphorylation and activity are mediated through an ERK-dependent mechanism. Moreover, COX-2-derived PGE(2) production appeared to involve in LPS-induced VCAM-1 expression which was attenuated by pretreatment with selective COX-2 inhibitors (NS-398 and celecoxib), transfection with COX-2 siRNA, or PGE(2) receptor antagonists. In addition, pretreatment with ecosapentaenoic acid (EPA), a substrate competitor of arachidonic acid (AA), also blocked LPS-induced VCAM-1 mRNA and protein expression, and THP-1 adherence. Collectively, these results suggest that LPS-induced VCAM-1 expression and adhesion of THP-1 cells are mediated through the TLR4/ERK/cPLA(2)alpha phosphorylation and COX-2 expression/PGE(2) synthesis in RASFs.
21299548 Pneumocystis jirovecii colonization in patients treated with infliximab. 2011 Mar BACKGROUND: Infliximab, a chimeric antitumour necrosis factor (TNF) monoclonal antibody, has become an established effective therapy for inflammatory rheumatic disease. However, TNF is a critical factor in host defence, and the suppression of its biological activity may be associated with the increased risk of opportunistic infections. The frequent use of infliximab in clinical practice has identified Pneumocystis jirovecii pneumonia (PcP) as a serious complication. Individuals colonized with Pneumocystis may be at high risk of development of PcP when they have undergone immunosuppression. Hence, we addressed the question of the frequency of Pneumocystis colonization among patients treated with infliximab. DESIGN: We examined 125 oropharyngeal washes collected from 78 individuals with rheumatoid arthritis, 30 with ankylosing spondylitis and 17 with psoriatic arthritis, half of them underwent infliximab therapy, using a real-time polymerase chain reaction assay that employs specific primers from a portion of the mitochondrial large-subunit rRNA gene of P. jirovecii. RESULTS: Pneumocystis jirovecii colonization was detected in 32 (25·6%) patients. In a multivariate regression model, only duration of infliximab treatment for more than 3 years and use of corticosteroid were significantly and independently associated with risk of Pneumocystis colonization. However, the effect of corticosteroid on P. jirovecii colonization rate was not linearly dose dependent as showed other logistic regression analysis. CONCLUSIONS: There is a high rate of P. jirovecii colonization among patients with rheumatologic diseases treated with infliximab. The identification of patients colonized by P. jirovecii before starting the treatment with infliximab could be a strategy for PcP prevention.
20235204 Electronic medical records for discovery research in rheumatoid arthritis. 2010 Aug OBJECTIVE: Electronic medical records (EMRs) are a rich data source for discovery research but are underutilized due to the difficulty of extracting highly accurate clinical data. We assessed whether a classification algorithm incorporating narrative EMR data (typed physician notes) more accurately classifies subjects with rheumatoid arthritis (RA) compared with an algorithm using codified EMR data alone. METHODS: Subjects with > or =1 International Classification of Diseases, Ninth Revision RA code (714.xx) or who had anti-cyclic citrullinated peptide (anti-CCP) checked in the EMR of 2 large academic centers were included in an "RA Mart" (n = 29,432). For all 29,432 subjects, we extracted narrative (using natural language processing) and codified RA clinical information. In a training set of 96 RA and 404 non-RA cases from the RA Mart classified by medical record review, we used narrative and codified data to develop classification algorithms using logistic regression. These algorithms were applied to the entire RA Mart. We calculated and compared the positive predictive value (PPV) of these algorithms by reviewing the records of an additional 400 subjects classified as having RA by the algorithms. RESULTS: A complete algorithm (narrative and codified data) classified RA subjects with a significantly higher PPV of 94% than an algorithm with codified data alone (PPV of 88%). Characteristics of the RA cohort identified by the complete algorithm were comparable to existing RA cohorts (80% women, 63% anti-CCP positive, and 59% positive for erosions). CONCLUSION: We demonstrate the ability to utilize complete EMR data to define an RA cohort with a PPV of 94%, which was superior to an algorithm using codified data alone.
20097032 Wear comparison between a highly cross-linked polyethylene and conventional polyethylene a 2011 Jan Highly cross-linked polyethylene (HXLPE) was developed to reduce wear of articular bearing surface in total hip arthroplasty patients. Several studies have shown reduced wear of HXLPE compared with conventional polyethylene; however, these studies had used HXLPE in combination with a Co-Cr metal head. The purpose of this study was to compare the 5-year in vivo wear of HXLPE with that of conventional PE using a zirconia femoral head. Forty-five hips with a Trilogy HXLPE (Zimmer, Warsaw, Ind) were matched and compared with a control group of 20 conventional Trilogy PE hips. The 2-dimensional linear wear rate was significantly less in the HXLPE group between 1 and 5 years postoperation (P < .001). The results show that HXLPE reduces short-term polyethylene wear against not only a Co-Cr head but also a zirconia head.
20008917 Can tumor necrosis factor inhibitors be safely used in pregnancy? 2010 Jan OBJECTIVE: We review available safety data for use of currently approved tumor necrosis factor (TNF) inhibitors during pregnancy and lactation and suggest guidelines for use of these agents among women of reproductive age. Method. Although regulatory agencies encourage the inclusion of pregnant women and those of child-bearing age in randomized controlled trials, pregnant and lactating women have universally been excluded from studies because of unknown or potential risks to the fetus. Thus, strong evidence-based treatment recommendations during pregnancy are usually lacking and safety information is derived from voluntary reports of adverse events during postmarketing surveillance or via uncontrolled, observational studies, reviewed here. RESULTS: Uncommon adverse pregnancy outcomes observed with TNF inhibitor therapy appear to approximate those seen in women not receiving such therapy and may include premature birth, miscarriage, low birthweight, hypertension, and preeclampsia. There are rare reports of fetal malformations or congenital anomalies in patients exposed to TNF inhibitors during conception or pregnancy. However, the incidence of these events appears to be far below the 3% rate of congenital anomalies in the general population. CONCLUSION: If the activity or disease severity precludes the cessation of a TNF inhibitor and/or DMARD, uncontrolled observations suggest that conception and early pregnancy are not adversely affected by use of TNF inhibitors. Nearly 70% of pregnant patients can discontinue their TNF inhibitor early in the pregnancy (or with determination of pregnancy) without augmenting maternal or fetal risks.
20007287 Positron emission tomography/computed tomography: a clinical tool for evaluation of enthes 2010 Feb OBJECTIVE: To evaluate the accuracy of PET/CT using [(18)F]fluorodeoxyglucose (FDG) in determining the presence of enthesitis in patients with SpAs. METHODS: Results of PET/CT scans of eight patients with SpA and seven patients with RA were retrospectively examined, with specific focus on five joints and three entheses. Volume fixation values are expressed as standardized uptake values (SUVs). Data from 20 patients with non-rheumatic (NR) diseases and 20 healthy subjects were also examined if non-specific, false positive findings were possible. We evaluated the clinical utility of PET/CT examinations in SpA, compared with MRI and Ga scintigraphy. RESULTS: Images of PET/CT scans of the shoulder, hip and knee joints revealed that FDG accumulated at the entheses in SpA and in the synovium in RA patients. The maximum SUVs [mean (s.d.)] were statistically higher in SpA patients compared with RA patients at the entheses of lumbar spinous process [4.83 (1.15) vs 1.42 (0.34); P < 0.05, respectively], pubic symphysis [3.93 (0.87) vs 1.35 (0.31); P < 0.05, respectively] and ischial tuberosity [4.76 (1.5) vs 1.35 (0.42); P < 0.05, respectively]. The positive frequencies of lumbar spinous processes and ischial tuberosity evaluated by PET/CT scan in the SpA group were significantly higher than that evaluated by MRI. CONCLUSION: MRI is now widely used to detect bone marrow oedema and enthesitis in patients with SpA. PET/CT scans offer an alternative method to identify enthesitis, and will likely contribute to the early diagnosis of SpA.
19318947 Environmental influences on risk for rheumatoid arthritis. 2009 May PURPOSE OF REVIEW: To examine new environmental factors and provide updates on known risk factors for rheumatoid arthritis (RA) in the past 2 years (2006-2008). This review is timely given the expanding information on treatment, pathogenesis and genetic risk factors for RA. RECENT FINDINGS: High consumption of red meat does not increase risk of RA, whereas alcohol intake may be protective. The role of vitamin D and oral contraceptives as modifiers of disease risk remains equivocal. Other factors associated with increased risk of RA include higher birthweight, living in the northeastern United States compared with other regions of the country, and lower socioeconomic status. Duration of breastfeeding is inversely associated with RA risk. Several studies have now demonstrated that anti-citrullinated protein antibody positive RA has a specific association with environmental risk factors such as smoking. SUMMARY: Recent studies have increased our understanding of environmental exposures that modify risk for RA such as smoking and alcohol intake. Other factors such as birthweight, breastfeeding, socioeconomic status and region of birth have also been demonstrated to contribute to risk. ACPA status is associated with specific environmental factors and is therefore important to incorporate into present and future studies.
19546078 [Effectiveness and safety of biological therapy with adalimumab]. 2009 Jun 28 Adalimumab is a human, recombinant antibody, which is effective in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriasis, arthritis psoriatica, spondylitis ankylopoetica, as well as with Crohn-disease. Adalimumab has got a high affinity binding to tumor necrosis factor (TNF-alfa), this way it inhibits the interactions with TNF and its receptors (soluble and membrane associated). It is well tolerated and safe, it improves the the quality of life. Possible side effects can be decreased by the careful observation and usual control of patients. The authors discuss in detail the publications on adalimumab in the above mentioned diseases.
21187298 Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 2011 May OBJECTIVES: To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. METHODS: A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. RESULTS: 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR 'good response' was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. CONCLUSIONS: Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period.