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ID PMID Title PublicationDate abstract
20306568 Subfulminant hepatitis B during treatment with adalimumab in a patient with rheumatoid art 2010 Apr We report a case of reactivation of hepatitis B virus (HBV) infection with subacute liver failure during administration of adalimumab, followed by a literature review of all 19 published cases, with a focus on the effect of antiviral prophylaxis. Eight patients were given prophylaxis and had a good outcome. Of the 11 patients without prophylaxis, six patients developed a reactivation and needed to stop anti-TNFalpha therapy (P = 0.017). One patient developed an acute liver failure, necessitating urgent liver transplantation. One patient died. Administration of anti-TNFalpha therapy can lead to HBV reactivation, with a possible lethal outcome. High-risk patients and possibly all patients should be screened for hepatitis B surface antigen and anti-HBV core antibody before starting anti-TNFalpha therapy. Administration of antiviral prophylaxis proves beneficial in prevention of reactivation in hepatitis B surface antigen positive patients.
20180636 Expression and activity profiling of selected cysteine cathepsins and matrix metalloprotei 2010 May Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. Their accumulation in synovial fluid of primarily rheumatoid arthritis patients is also well documented. However, a detailed comparison between the protease levels and activities between rheumatoid arthritis samples and osteoarthritis samples has never been made. Here, we report that both cysteine cathepsins B and S and matrix metalloproteases-1, -3 and -13 are detected in patient synovial fluid samples with significantly higher levels detected in rheumatoid arthritis patients. Among the proteases, cathepsin S was found to be significantly elevated, consistent with its critical role in the immune response. These results suggest that cysteine cathepsins have a major role in inflammation at least in rheumatoid arthritis. In addition to proteases, interleukin-6 was detected at significant levels in most samples, suggesting that proinflammatory cytokines might be in-volved in the stimulation of expression of these proteases during inflammation.
20028730 Evaluation of three automated enzyme immunoassays for detection of anti-cyclic citrullinat 2010 Mar OBJECTIVE: The anti-cyclic citrullinated peptide (anti-CCP) antibody has been increasingly used in the field of rheumatology, and various manufacturers have developed a variety of anti-CCP assays using mainly ELISA techniques. This study evaluated the performance of recently marketed automated chemiluminescence enzyme immunoassays for anti-CCP. METHODS: We investigated four anti-CCP assays (Diastat anti-CCP ELISA assay, Axsym anti-CCP assay on the Axsym system, the Architect anti-CCP assay on the Architect i2000 system and the Elecsys anti-CCP assay on the Cobas e 411 analyzer). Samples from 64 patients with RA and 152 controls, including patients with various autoimmune diseases, were studied. We assessed the clinical sensitivities and specificities, and compared the qualitative and quantitative results of each anti-CCP assay. RESULTS: Using the manufacturers' cut-off, diagnostic sensitivities ranged from 90.6 to 93.8% and the specificities ranged from 85.5 to 86.8%. The areas under the curve were comparable among the different assays, and qualitative agreements ranged from 97.2 to 99.1%. In the quantitative results, all anti-CCP assays were significantly correlated (P < 0.001), but the correlation coefficient ranged from 0.615 to 0.861. Especially, the correlation coefficients between the automated anti-CCP assays were higher than those between the ELISA assay (Diastat) and the automated assays. CONCLUSIONS: The overall diagnostic performance of the automated anti-CCP assays was comparable, and it provides reliable information on antibody levels, making them useful in monitoring disease activity.
19909776 Beyond oncology--application of HPMA copolymers in non-cancerous diseases. 2010 Feb 17 Macromolecular drug conjugates have been developed to improve the efficacy and safety profile of various therapeutic agents for many years. Among them, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates are the most extensively studied delivery platforms for the effective treatment of cancer. In recent years, the applications of HPMA copolymers for the treatment of a broader range of non-cancerous diseases have also been explored. This review highlights the recent developments in the rational design, synthesis, and evaluation of novel HPMA copolymer-drug conjugates for non-cancerous diseases, such as musculoskeletal diseases, infectious diseases and spinal cord injury. The translation potential of these applications is also briefly discussed.
19404945 The good initial response to therapy with a combination of traditional disease-modifying a 2009 May OBJECTIVE: To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission. RESULTS: At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. CONCLUSION: Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.
20824423 [Angiographic diagnosis of acral circulatory disorders of the upper extremities]. 2010 Oct Acral ischemic lesions rarely affect the upper extremities. While in the lower limbs atherosclerosis is responsible for the majority of lesions, vasculitis and autoimmune diseases play an important role in the pathogenesis of ischemic lesions of the upper limbs. A considerable number of acral circulatory disorders present with Raynaud's phenomenon and often without associated necrosis. Raynaud's phenomenon is mainly idiopathic but may also be secondary to underlying conditions, such as autoimmune diseases and vasculitis. Because of its high spatial resolution and the often discrete morphological findings digital subtraction angiography (DSA) is still an important diagnostic method in the radiological evaluation of acral circulatory disorders of the hand. Angiographic features of vasculitis are not strictly pathognomonic but certain morphologic DSA findings are very typical and may allow for a radiologic diagnosis. For instance, atherosclerosis results in irregular contours of vessel walls in DSA in contrast to autoimmune diseases and vasculitis, which are usually characterized by smooth vessel walls and optional vasospasm, the latter being especially typical for thromboangiitis obliterans and scleroderma. In thromboangiitis obliterans occlusions of the distal hand arteries, corkscrew collateral vessels and subsequent development of fine collateral networks are typical findings. Abrupt or filiform occlusions of distal finger arteries with sparse collateralization and symmetric affection of both hands are suggestive of scleroderma. Disseminated segmental ectasis and stenosis as well as microaneurysms (63% of all patients) are very common in patients with panarteriitis nodosa.
21068094 Anti-citrullinated protein antibodies have a low avidity compared with antibodies against 2011 Feb OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Recent ongoing evidence indicates that the ACPA response broadens before precipitation of full-blown RA, as indicated by a more extensive isotype usage and an increased citrullinated epitope recognition profile. Nonetheless, the evolution of the ACPA response is still poorly understood and might intrinsically differ from the protective responses against pathogens. METHODS: The avidity and the avidity maturation of ACPA in relation to the avidity of antibodies against recall antigens were analysed. RESULTS: The avidity of ACPA was significantly lower than the avidity of antibodies to the recall antigens tetanus toxoid and diptheria toxoid. Moreover, ACPA did not show avidity maturation during longitudinal follow-up and ACPA avidity was also relatively low in patients who displayed extensive isotype switching. CONCLUSIONS: These observations indicate that the natural evolution of ACPA differs from the development of antibodies against recall antigens. These data also indicate that ACPA avidity maturation and isotype switching are disconnected, whereby extensive isotype switching occurs in the setting of restricted avidity maturation. Intrinsic differences between the RA-specific autoantibody system and protective antibody responses against pathogens could be of relevance for designing novel B cell-targeted therapies for RA.
20149307 High rates of stopping or switching biological medications in veterans with rheumatoid art 2009 Nov OBJECTIVES: To define the characteristics of a population of veterans with rheumatoid arthritis (RA) who have stopped or switched their first biologic agent, and to assess if measures of disease activity are predictors in the decision to alter the regimen. METHODS: A retrospective analysis of the VA electronic medical record system identified RA patient demographic and disease activity parameters from 1999 to 2007. Demographic data included age, race/ethnicity, sex, and tobacco use. Disease-specific data included date of RA onset, past DMARD therapies, prednisone use, as well as the disease activity score (DAS-28) and the health assessment questionnaire (HAQ) at each clinic visit. The use of six biologicals (infliximab, etanercept, adalimumab, abatacept, rituximab, anakinra) was identified in order to compare those who continued with the medication to those discontinuing or switching to another biological. Descriptive and parametric statistics were applied to define differences between the two groups. RESULTS: Of 454 RA patients identified, 212 have been on a biologic agent at one point in time, and 100 patients (47%) had either stopped or switched their first biologic agent. Among these 100 patients, the most common reasons for stopping or switching a biologic agent were adverse events (in 48%) and inefficacy (43%) Adverse events included malignancies (23% of 48 patients), rash (23%), infections (18.8%), and cardiac complications (18.8%). When comparing the 100 patients versus the 112 that did not stop or switch their first agent, the DAS-28 correlated significantly with a change of regimen with an OR 2.1 (p<0.001). The HAQ score had an OR of 2.0 (p<0.04). CONCLUSION: RA patients who continue taking their initial biologic medication have similar age, RA disease duration, ethnicity, and smoking status to those requiring switching or discontinuation. The DAS28 and HAQ scores significantly correlated with stopping or switching of a first biologic agent. Adverse event rates were high and their distributions differed in this population compared to previous studies of younger Caucasian females.
19721344 [Triggering receptor expressed on myeloid cells-1 as an inflammation amplifier]. 2009 Aug Triggering receptor expressed on myeloid cells (TREM)-1 is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in diseases related to bacterial infection. Its blockade suppressed fatal immune responses in mice models of sepsis without impairing the host defense. However, the influence of TREM-1 on non-bacterial diseases was not elucidated. We describe here that TREM-1 expression was up-regulated by prostaglandin (PG) E(2) as well as lipopolysaccharide. Activation of TREM-1 expressed on PGE(2)-pretreated peripheral blood mononuclear cells by an agonistic TREM-1 mAb significantly enhanced the production of TNFalpha. Indeed, monosodium urate monohydrate (MSU) crystals induced TREM-1 expression in vitro and in vivo. MSU crystals and an anti-TREM-1 agonistic antibody synergistically increased the production of interleukin-1beta compared with stimulation with the crystals alone. Furthermore, TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with collagen-induced arthritis (CIA). Blockade of TREM-1 ameliorated CIA without affecting T cell and B cell immune responses to the inducing antigen. These results provide evidence that TREM-1 may contribute the development of non-microbial inflammatory diseases through the enhancement of inflammatory responses.
20810033 Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST- 2010 Jul OBJECTIVES: To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. METHODS: Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. RESULTS: A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. CONCLUSIONS: BMI appears to be associated with RA disease activity in women, but not in men.
20506254 Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis w 2010 Aug OBJECTIVE: To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug. METHODS: This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (i.v.) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated. RESULTS: AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24. CONCLUSION: Our findings indicate that ofatumumab, administered as 2 i.v. infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.
19362504 Effect of discontinuing TNFalpha antagonist therapy in patients with remission of rheumato 2009 Jul OBJECTIVE: The objective of this study was to determine the time to relapse after tumor necrosis factor alpha (TNFalpha) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA). METHODS: Among 304 patients taking TNFalpha antagonist therapy for RA, 21 achieved a remission and were taken off the TNFalpha antagonist. Remission was defined as DAS28<2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFalpha antagonist was restarted in the event of a relapse (DAS28>3.2). RESULTS: The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFalpha antagonist discontinuation of 19.2 months. The TNFalpha antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFalpha antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFalpha antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFalpha antagonist therapy (56 months vs. 35 months, P=0.012) and a longer time in remission on TNFalpha antagonist therapy (35 months vs.14.5 months, P=0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFalpha antagonist therapy; the remission occurred within 2 months in 13 patients. CONCLUSION: TNFalpha antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFalpha antagonist.
20334454 Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the 2010 Apr STUDY OBJECTIVE: To evaluate the efficacy and safety of using the anti-tumor necrosis factor-alpha (anti-TNF-alpha) drugs adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. DESIGN: Systematic review and meta-analysis of 21 randomized, placebo-controlled trials (eight adalimumab, seven infliximab, six etanercept). PATIENTS: Adults with rheumatoid arthritis who received adalimumab (1524 patients), infliximab (1116 patients), etanercept (1029 patients), or placebo (2834 patients) with or without concomitant methotrexate in all groups. MEASUREMENTS AND MAIN RESULTS: A literature search of several databases from January 1995-December 2008 was performed. There were no restrictions based on language or date of publication, and low-quality studies (based on Jadad score) were excluded. American College of Rheumatology (ACR) 20% improvement criteria (ACR20), 50% improvement criteria (ACR50), and 70% improvement criteria (ACR70) were used to compare treatment efficacy. Safety was compared based on frequency of serious adverse events, serious infections, malignancy, and death. Withdrawals due to adverse events and lack of efficacy were also evaluated. With short-term treatment (12-30 wks), etanercept demonstrated the highest risk ratios (RRs) for reaching ACR20 and ACR50: 2.94 (95% confidence interval [CI] 2.27-3.81) and 5.28 (95% CI 3.12-8.92), respectively. Adalimumab demonstrated the highest RR for achieving ACR70 (5.36, 95% CI 3.76- 7.64). Over a long-term treatment course (1-3 yrs), adalimumab demonstrated the highest RRs (95% CIs) for these parameters: 1.85 (1.07-3.19), 2.80 (1.16-6.77), and 3.23 (1.37-7.61) for ACR20, ACR50, and ACR70, respectively. No statistically significant differences were noted in the safety of any of the three drugs compared with placebo. Infliximab had the highest RRs for withdrawing from the study due to lack of efficacy (2.05, 95% CI 1.33-3.16) and adverse events (0.41, 95% CI 0.18-0.95). CONCLUSION: With short-term treatment, etanercept and adalimumab had higher efficacy results; with long-term treatment, adalimumab appeared to be the most effective. Clinicians should be aware that each of the three drugs has different rates of efficacy and different safety considerations that must be taken into account when selecting the best treatment for an individual with rheumatoid arthritis.
20610315 Tocilizumab: therapy and safety management. 2010 Jun OBJECTIVES: To develop fact sheets about tocilizumab, in order to assist physicians in the management of patients with inflammatory joint disease. METHODS: 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The 20 experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of RA. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several. experts and the overall process was coordinated by three experts. RESULTS: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of tocilizumab therapy, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. CONCLUSION: These tocilizumab fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on tocilizumab therapy. They will be available continuously at www.cri-net.com and updated at appropriate intervals.
19585384 Rituximab therapy in patients with rheumatoid arthritis refractory or with contraindicatio 2009 OBJECTIVES: To describe the effects of rituximab therapy in patients with rheumatoid arthritis (RA) in routine clinical practice in Finland. METHODS: Data were collected retrospectively from patient records in five rheumatology clinics in Finland. All RA patients treated during 2005-2008 (n = 81) were included. Information on disease-modifying anti-rheumatic drugs (DMARDs), DMARD combinations, and biologics prior to rituximab use was collected as well as treatment responses after initiating rituximab therapy. The Disease Activity Score using 28 joint counts (DAS28) was used to determine disease activity and European League Against Rheumatism (EULAR) responses. RESULTS: Mean disease duration was 14 (range 0-47) years and the median number of prior DMARDs and biologics used were 7 (1-12) and 2 (0-4), respectively. Efficacy analysis was performed on 57 patients with available DAS28 data at treatment onset and follow-up visits. Median DAS28 declined from 6.07 (3.19-7.70) to 3.99 (1.53-6.55) by the first rituximab treatment course. Altogether 77% of the patients achieved a EULAR response, 26% with a good response including 18% with remission. Furthermore, the patients treated concomitantly with DMARDs other than methotrexate (MTX) achieved a EULAR response slightly more often than the patients on MTX (85% vs. 70%) only. A second course of rituximab was given to 48% of the patients on an average of 9 months after initial therapy, with the median DAS28 score declining further to 3.49 (0.1-5.74). Safety and tolerability assessment of the 81 patients indicates rituximab to be well tolerated. CONCLUSIONS: Rituximab can effectively control disease activity in patients with active disease and poor response to previous therapies, in combination with MTX but also with other DMARDs.
20194448 Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous ina 2010 May OBJECTIVE: To assess the efficacy and safety of 1 versus 2 courses of rituximab over 48 weeks in patients with rheumatoid arthritis (RA). METHODS: Adult patients taking methotrexate with a previous inadequate response to > or = 1 tumor necrosis factor inhibitor received 1 course of open-label rituximab (2 x 1000 mg IV) at baseline. From Week 24, patients were randomized to receive an additional course of retreatment with rituximab or placebo. Efficacy responses at Week 48 relative to baseline were assessed. RESULTS: Of 559 patients who received the open-label first course of rituximab, 475 patients were randomized to a second course (rituximab retreatment: n = 318, placebo retreatment: n = 157). Relative to baseline, patients who took rituximab during retreatment had significantly improved efficacy at Week 48 compared to patients who took a placebo during retreatment [American College of Rheumatology (ACR20) criteria, 54% vs 45%, p = 0.02; change in Disease Activity Score-28 mean -1.9 vs -1.5, p = 0.006]. Differences in efficacy between groups were first observed following Weeks 28-32. Worsening of most components of the ACR core set occurred in the placebo-retreated patients with relative maintenance of these measures in rituximab-retreated patients. Randomized patients who had achieved week 24 ACR responses following the first course had greater odds of losing response if retreated with placebo (odds ratios for ACR20, ACR50, ACR70: 2.09, 2.03, and 4.09, respectively). Following retreatment, the proportion of patients experiencing any adverse events (AE), serious AE, infections, and serious infections were comparable between the rituximab and placebo retreatment groups. CONCLUSION: Two courses of rituximab about 6 months apart resulted in improved and sustained efficacy at 1 year, compared with 1 course, with a similar safety profile.
19127365 Single center prospective study of tacrolimus efficacy and safety in treatment of rheumato 2009 Feb The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus for treating rheumatoid arthritis (RA) patients in clinical practice. Fifty-five active RA patients who had been resistant or intolerant to other disease-modifying antirheumatic drugs were enrolled in this open-label trial. Patients were administered tacrolimus at a dosage of 1, 2 or 3 mg once daily, and followed up for 24 weeks. They were divided into three groups according to their dosage. Efficacy and safety were evaluated utilizing clinical and laboratory findings. Eighty percent of the patients had moderate or high disease activity; 55% were elderly and 53% had complications; 65% of the patients were started on tacrolimus as a monotherapy. Moderate or good response rates were achieved as follows: 38.2% (4 weeks); 41.8% (12 weeks); and 45.6% (24 weeks). Adverse events were observed in seven cases (12.7%). Only one case required hospitalization due to severe hyperglycemia caused by a high tacrolimus concentration (24.2 ng/ml); we suspected a drug interaction in this subject. Mean concentrations were dose-dependent in the 1, 2, and 3 mg/day groups (2.96, 4.29, and 8.32 ng/ml, respectively). Four cases of high concentration (over 10 ng/ml), without any signs or symptoms, were observed in the 3 mg/day group; in these cases, doses were decreased and no severe adverse events occurred. Tacrolimus was found to be both effective and safe in treating active RA patients with complicated backgrounds in clinical practice. Blood concentration measurements and dose adjustments should be performed to prevent severe adverse events in a 3 mg/day group.
20682662 Lack of association of C-C chemokine receptor 5 Δ32 deletion status with rheumatoid arthr 2010 Nov OBJECTIVE: C-C chemokine receptor 5 (CCR5) plays an important role in inflammation. A 32 base-pair (Δ32) deletion in the CCR5 gene leads to a nonfunctional receptor. This deletion has been reported to have a protective effect on the development and progression of several autoimmune diseases. We investigated whether the Δ32 deletion is associated with disease susceptibility in a population of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is associated with disease severity. METHODS: DNA samples from 405 RA patients, 97 SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the CCR5 Δ32 deletion. Differences in genotype frequencies were tested between patients and controls. Association of genotypes with disease severity was analyzed. RESULTS: Genotype frequencies of each group were in Hardy-Weinberg equilibrium. The genotype frequencies of patients did not differ significantly from controls (CCR5/Δ32, Δ32/Δ32: RA 18.3% and 1.2%, respectively; SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there was a trend for lower Δ32 deletion allele frequency in LN patients compared to controls (p = 0.08). There was no significant association between the CCR5 status and disease severity in RA, SLE, or LN. CONCLUSION: Although an association with LN cannot be excluded, the CCR5 Δ32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect of the Δ32 deletion on disease severity was demonstrated.
20091032 Activities of daily living after total hip arthroplasty. Is a 32-mm femoral head superior 2011 Jan Range of motion (ROM) of the hip joint after total hip arthroplasty (THA) could be increased by using a larger prosthetic femoral head, but it is not known whether the activities of daily living (ADL) are influenced by THA with different head sizes. Our objective was to compare postoperative ADL in patients who underwent THA using a head diameter of 26 mm or 32 mm. We assessed the range of motion and the mode of ADL after cementless primary THA. Comparison was performed between 25 joints of 24 patients who underwent THA with a 26-mm femoral head (26-mm group) and 24 joints of 20 patients with a 32-mm head (32-mm group). The postoperative range of flexion and abduction was significantly larger in the 32-mm group than in the 26-mm group. With respect to the mode of performing selected ADL such as putting on and removing pants, socks, and cutting toenails, many patients adopted the compensatory position of lumbar flexion with hip flexion plus knee extension in the 26-mm group, while a majority of the patients from the 32-mm group employed the mode of hip flexion with knee flexion. Patients with the 32-mm head showed better postoperative ADL of the ipsilateral side compared with the 26-mm head.
19697097 Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheu 2009 Oral tolerance means a diminished immune response to previously fed antigens. Repeated oral administrations of type II collagen (CII) induce oral tolerance and inhibit the development of collagen-induced arthritis (CIA). Dendritic cells (DCs) in the gut-associated lymphoid tissue (GALT) take up the CII and then present it to T cells to generate regulatory T cells (Tregs), which induce systemic immune tolerance to CII. Inhibitory cytokines, such as transforming growth factor (TGF)-beta and interleukin (IL)-10, and several immune regulatory molecules, including indoleamine 2,3-dioxygenase (IDO) and retinoic acid, play an important role in Treg generation. Each DC subset may play different roles, and CD11c+CD11b+DCs and IDO+DCs are important in the generation of antigen-inducible Tregs in CII oral tolerance. Upon stimulation with the antigen involved in its generation, Treg is activated and regulates the immune response through inhibitory cytokine production, cell-to-cell contact-dependent mechanisms, DC modification, and bystander suppression. The DCs and Tregs are deeply involved in oral tolerance through reciprocal interactions. Several clinical trials have been conducted in RA patients to examine the efficacy of CII oral tolerance. An understanding the mechanism of oral tolerance to CII would give clinicians new insights into the development of natural immune tolerance and new therapeutic approaches for the treatment of autoimmune diseases.