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ID PMID Title PublicationDate abstract
18634163 Effect of anakinra on functional status in patients with active rheumatoid arthritis recei 2008 Aug OBJECTIVE: To assess changes in functional status in patients with rheumatoid arthritis (RA) receiving the interleukin-1 receptor antagonist anakinra in addition to a disease modifying antirheumatic drug (DMARD). METHODS: In this large, multicenter, open-label, single-arm study, adult patients with RA receiving methotrexate, sulfasalazine, or hydroxychloroquine for > or = 3 months were given anakinra 100 mg once daily for up to 36 weeks. The primary objective was to evaluate changes from baseline to week 36 in the Health Assessment Questionnaire (HAQ) disability index and subscales. Changes in the 28-joint Disease Activity Score (DAS28), proportion of patients meeting European League Against Rheumatism (EULAR) response criteria, and the safety of each combination regimen were also assessed. RESULTS: A total of 1207 patients were enrolled, received > or = 1 dose of anakinra, and were included in the efficacy and safety analyses. A statistically significant change in the HAQ disability index was observed (p = 0.0001); no significant differences were seen among the 3 DMARD groups. A clinically meaningful improvement in HAQ (> 0.22) was observed in 51% of patients. Mean improvement in DAS28 was 1.5 (p < 0.0001), and 64% of patients achieved a good or moderate EULAR response score. Injection site reaction was the most frequently (62%) reported adverse event. The incidence of infections (24%), most commonly respiratory infection, was similar across treatment groups. No notable changes were observed in laboratory findings and vital signs. CONCLUSION: These findings indicate that anakinra 100 mg/day in combination with DMARD therapy safely improved functional status in patients with active RA.
18543055 The predictors of foot ulceration in patients with rheumatoid arthritis: a preliminary inv 2008 Nov We explored the predictors of foot ulceration in patients with rheumatoid arthritis (RA). The cases were 15 patients with RA reporting foot ulceration in response to a postal survey of patients sampled from a diagnostic register in secondary care (n = 1,130). The controls were 66 patients with RA randomly sampled from the survey respondents (n = 883) after matching for age, sex and disease duration. Patients with co-existent diabetes were excluded. Clinical examination included the assessment of known risk factors for foot ulceration in diabetes including: neuropathy (insensitivity to 10 g monofilament), peripheral vascular disease (ankle brachial pressure index [ABPI]), foot deformity (Platto indices) and raised plantar pressure (PressureStat readings). A 44 swollen-joint count, the presence of pre-ulcerative lesions and current steroid therapy were identified through univariate analysis as additional potential predictors in patients with RA. Forward step-wise logistic regression analysis showed that the following variables were significant predictors of ulceration: steroid therapy (OR = 9.70, 95%CI = 2.09-45.11, p = 0.004), abnormal ABPI (OR = 13.45, 95%CI = 1.19-151.43, p = 0.035), the presence of pre-ulcerative lesions (OR = 7.40, 95%CI = 1.51-36.30, p = 0.014) and swollen-joint count (OR = 1.25, 95%CI = 1.02-1.53, p = 0.034). Abnormal sensation, foot deformity and raised plantar pressures were not significant predictors of ulceration. The wide confidence intervals for ABPI were due to sparse data with very few abnormal values, and the results of exact logistic regression (more accurate where data is sparse and case matching employed) found that ABPI was no longer a significant predictor (p = 0.054). The significance of the other predictors did not differ substantially. In this preliminary study, abnormal sensation, foot deformity and raised plantar pressures were not significantly associated with foot ulceration but active disease and current steroid therapy were. The contribution of peripheral vascular disease to risk is unclear and further investigation is needed in a larger cohort.
18535759 Discontinuation of infliximab in rheumatoid arthritis patients in clinical remission. 2008 Biologic drugs are effective but are also expensive, and it is difficult to evaluate the duration of treatment. Infliximab, an anti-TNFalpha antibody, suppresses arthritic activity and inhibits bone destruction in patients with rheumatoid arthritis (RA). Here, we document that infliximab could be discontinued after clinical remission in RA patients. Among 172 patients with RA who reached clinical remission following infliximab (3 mg/kg) and methotrexate (MTX, >6 mg/w), nine patients with sustained remission discontinued it. Clinical assessment was based on a disease activity score (DAS) that included a 28-joint count/erythrocyte sedimentation rate (DAS28-ESR). The disease was assessed before and after the start of infliximab treatment, and concomitant drug treatment-in the order of corticosteroid, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) other than MTX-was gradually discontinued. We considered patients for discontinuation of infliximab treatment after remission (DAS28-ESR<2.6) had been sustained for more than 24 weeks. The nine patients able to discontinue treatment were all females, with a mean age of 53.8 years; eight patients were at stage I or II. The mean duration of disease was 28.7 months, and these patients were on corticosteroid treatment equivalent to a mean of 2.28 mg prednisolone (PSL). These nine patients all met the remission standard-that DAS28-ESR<2.6 for >or=24 weeks) -and so their treatment with concomitant drugs was discontinued. After the discontinuation of infliximab, the mean period of sustained remission was 14.2 months and the longest period was 29 months. The duration of disease was significantly shorter and the points from Steinbrocker's stage-classification were significantly lower in the infliximab-discontinued group than in the infliximab-continued group. Strategic reductions and/or discontinuations of concomitant treatment were performed in RA patients who attained clinical remission (DAS28<2.6) through treatment with infliximab and MTX. Nine patients successfully discontinued infliximab after maintaining clinical remission for more than 24 weeks. After infliximab was discontinued, clinical remission and suppression of joint destruction were maintained with MTX alone, especially in early RA patients.
16644782 Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumat 2006 Nov BACKGROUND: Polymyalgia rheumatica (PMR) may create some difficulties in the differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA with PMR-like onset (EORA/PMR). AIM: To investigate possible differences between three groups of patients, with regard to serum levels of inflammatory cytokines and steroidal hormones at baseline and after 1 month of treatment with glucocorticoids (prednisone 7.5-12.5 mg/day). PATIENTS AND METHODS: 14 patients with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched controls were analysed. Tumour necrosis factor alpha (TNFalpha), interleukin (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. RESULTS: Serum levels of both TNFalpha and IL6 were significantly higher in all three groups of patients than in controls (p<0.01). Serum IL6 levels were significantly higher in patients with both PMR and EORA/PMR than in patients with EORA (p<0.05). IL1Ra serum levels were significantly higher in patients with EORA than in controls (p<0.001) and in patients with PMR and EORA/PMR (p<0.05). DHEAS was significantly lower in patients with EORA/PMR than in those with EORA (p<0.05). PRG was significantly higher in all patient groups (p<0.05). After glucocorticoid treatment, serum TNFalpha and IL6 levels significantly decreased in all patient groups; IL1Ra significantly increased in patients with PMR and in those with EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR and in those with EORA/PMR (p<0.05). CONCLUSIONS: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA.
17181919 Polymerized-type I collagen for the treatment of patients with rheumatoid arthritis. Effec 2006 Sep OBJECTIVE: To determine the efficacy, tolerance and safety of intramuscular injections of porcine type I collagen-PVP in patients with RA in a long term-therapy. METHODS: The study was a double blind placebo-controlled and included 30 patients with active RA (ACR). Patients were treated with intramuscular injections of 2 ml of collagen-PVP (3.4 mg of collagen) or 2 ml of placebo during 6 months. The follow up was done during the next 6 months. The primary endpoints included the Ritchie index (RI), swollen joint count, disease activity score (DAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The secondary endpoints included morning stiffness, pain intensity on a visual analogue scale (VAS), and Spanish-health assessment questionnaire (HAQ-DI). Improvement was determined using American College of Rheumatology response criteria (ACR20, 50 and 70). RESULTS: Collagen-PVP was safe and well tolerated. There were no adverse events. Patients had a statistically significant improvement (p < 0.05) in collagen-PVP-treated vs. placebo at 6 months of treatment in: swollen joint count (7.1 +/- 0.8 vs. 16.0 +/- 1.6), RI (8.1 +/- 0.8 vs. 15.2 +/- 1.5), morning stiffness (9.2 +/- 3.1 vs. 29.1 +/- 5.9 min), HAQ-DI (50.0 +/- 10.8 vs. 22.9 +/- 10.3), DAS (3.0 +/- 0.2 vs. 4.9 +/- 0.3), ACR20 (78.6 vs. 71.4%), ACR50 (57.1 vs. 0%) and ACR70 (7.1 vs. 0%) and CRP (1.1 +/- 0.4 vs. 2.5 +/- 0.7). Patients treated with collagen-PVP required lower doses of methotrexate vs. placebo (12.6 +/- 0.6 vs. 14.2 +/- 0.7 at 6 months and 12.3 +/- 0.8 vs. 15.4 +/- 0.6 at 12 months; p < 0.05). Serological or haematological parameters remained unchanged. CONCLUSION: Collagen-PVP has been shown to be a safe and well-tolerated drug for the long-term treatment of RA. Combination of collagen-PVP plus methotrexate was more efficacious than methotrexate alone. This biodrug can be useful in the treatment of RA.
16869978 Predictors of infusion reactions during infliximab treatment in patients with arthritis. 2006 In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999-2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions.
17105646 Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes. 2006 Fibroblast activation protein (FAP), as described so far, is a type II cell surface serine protease expressed by fibroblastic cells in areas of active tissue remodelling such as tumour stroma or healing wounds. We investigated the expression of FAP by fibroblast-like synoviocytes (FLSs) and compared the synovial expression pattern in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Synovial tissue from diseased joints of 20 patients, 10 patients with refractory RA and 10 patients with end-stage OA, was collected during routine surgery. As a result, FLSs from intensively inflamed synovial tissues of refractory RA expressed FAP at high density. Moreover, FAP expression was co-localised with matrix metalloproteinases (MMP-1 and MMP-13) and CD44 splice variants v3 and v7/8 known to play a major role in the concert of extracellular matrix degradation. The pattern of signals appeared to constitute a characteristic feature of FLSs involved in rheumatoid arthritic joint-destructive processes. These FAP-expressing FLSs with a phenotype of smooth muscle actin-positive myofibroblasts were located in the lining layer of the synovium and differ distinctly from Thy-1-expressing and non-proliferating fibroblasts of the articular matrix. The intensity of FAP-specific staining in synovial tissue from patients with RA was found to be different when compared with end-stage OA. Because expression of FAP by RA FLSs has not been described before, the findings of this study highlight a novel element in cartilage and bone destruction of arthritic joints. Moreover, the specific expression pattern qualifies FAP as a therapeutic target for inhibiting the destructive potential of fibroblast-like synovial cells.
17133578 Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis. 2006 Dec OBJECTIVE: Recent findings suggest that interferon regulatory factor 5 (IRF-5) may play a crucial role in several cellular processes, including the transcription of genes for inflammatory cytokines. Two genetic variants of the IRF5 gene (rs2004640 in exon 1 and rs2280714 in the 3'-untranslated region) have been shown to exert functional modifications affecting IRF5 messenger RNA splicing and expression, and have been associated with genetic predisposition to systemic lupus erythematosus (SLE). The aim of this study was to analyze the possible contribution of the IRF5 gene to the predisposition to rheumatoid arthritis (RA). METHODS: Three case-control cohorts from Spain (724 RA patients and 542 healthy controls), Sweden (281 RA patients 474 healthy controls), and Argentina (284 RA patients and 286 healthy controls) were independently analyzed. Genotyping for IRF5 rs2004640 and rs2280714 was performed using a TaqMan 5' allele-discrimination assay. RESULTS: In the 3 cohorts studied, no statistically significant differences in allele or genotype frequencies of the rs2004640 and rs2280714 IRF5 polymorphisms were observed between RA patients and controls. Accordingly, haplotype analysis revealed that none of the IRF5 haplotypes was associated with genetic predisposition to RA. CONCLUSION: Our results suggest that the IRF5 functional polymorphisms analyzed do not seem to be implicated in genetic susceptibility to RA.
18951301 Atacicept, a homodimeric fusion protein for the potential treatment of diseases triggered 2008 Nov Atacicept (TACI:Fc5) is a homodimeric fusion protein obtained through recombinant DNA technology being developed by Merck Serono SA, under license from ZymoGenetics Inc, for the potential treatment of B-cell diseases. Atacicept is undergoing phase II/III clinical trials for systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, multiple sclerosis, as well as for several B-cell malignancies.
17594118 Chloroquine ototoxicity. 2007 Nov Chloroquine (CQ), a 4-aminoquinoline drug, has been largely used for the treatment of rheumatoid arthritis and other connective tissue diseases. Besides the well-known retinal toxicity, its use has been suspected of be associated to ototoxicity. Some reports have described mainly sensorineural hearing loss, tinnitus, sense of imbalance, and cochleovestibular manifestations. Differently from what occurs in retinopathy, in which there is a predominance of CQ toxicity, there are reports of alterations in hearing related to either CQ or hydroxychloroquine. Brain-evoked response audiometry seems to be the most sensitive test in detecting early manifestations of cochlear injury caused by CQ when still in a reversible stage. The reversibility of CQ ototoxicity has been debatable, but there is suggestion that such complication can be corrected if the medication is stopped and appropriate therapy, with steroids and plasma expanders, is instituted.
16467038 Prevalence and clinical correlates of anti-phospholipid antibodies in South Africans with 2006 Jan OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.
17828341 "The Leeds Idea": an historical account of the spondarthritis concept. 2007 In the 1960s, Professor Verna Wright became increasingly interested in possible relationships between certain seronegative "variants of rheumatoid arthritis", as they were then generally known. At the Rheumatism Research Unit, a department within the division of medicine at Leeds University, he gathered around him a succession of research workers, whom he inspired to study aspects of these relationships. The focus was on family studies, as it was thought that genetic factors could be important. The striking association previously noted between sacroiliitis or full-blown ankylosing spondylitis and several of these disorders to be studied - e.g., psoriatic arthritis, ulcerative colitis, and the arthritis associated with Crohn's disease - was to be central for each of these studies. As a provisional collective name for these possibly related conditions, the term "Spondarthritides" was chosen. These were the days before HLA B27, and so the research tools were simply clinical, radiological (for sacroiliitis) and serological (for rheumatoid factor). The research programme confirmed not only links between the primary disorders with ankylosing spondylitis, but also links between the disorders themselves. Over subsequent years, the spondarthritis concept (dubbed by some "The Leeds Idea") has gained further strength from HLA studies internationally. And membership of the group of conditions fulfilling spondarthritis criteria has grown substantially. It is hoped that this now consolidated framework of spondylitis-related entities will pave the way for further research, with exciting prospects of gene-based prevention and/or cure through the increasing sophistication of molecular biology.
16428214 Survival and complications are similar after Swanson and Sutter implant replacement of met 2006 We compared the survival, fracture, and deformation rates of Swanson and Sutter implants in a prospective series of 53 patients with rheumatoid arthritis (RA). Fifty-eight hands were operated on with 215 silastic implants. The Swanson group comprised 25 hands and 89 implants, and the Sutter group 33 and 126, respectively. Follow up was 58 (37-80) months. During a period of 48 months the survival of Swanson and Sutter prostheses did not differ significantly: 92% (95% CI 84% to 96%) and 97% (95% CI 92% to 99%), respectively. The fracture rate was high in both groups: 26 (34%) in the Swanson and 25 (26%) in the Sutter group. There was no significant difference between the groups in definite fracture rates of implants. The Sutter prosthesis appears to be at least as durable an implant in rheumatoid patients' metacarpophalangeal arthroplasty as the Swanson.
18635594 Multiple antibody reactivities to citrullinated antigens in sera from patients with rheuma 2009 May BACKGROUND: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. OBJECTIVE: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. METHODS: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, alpha-enolase peptide-1 and the C1-epitope of type II collagen (C1(III)). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. RESULTS: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated alpha-enolase peptide-1 and citrullinated C1(III). These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles. CONCLUSIONS: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.
17133360 CCL20 chemokine induces both osteoblast proliferation and osteoclast differentiation: Incr 2007 Mar We evaluated the role of CCL20 (MIP-3alpha) chemokine in cells directly involved in the remodeling of bone tissue (osteoblasts and osteoclasts) and we confirmed its expression in the subchondral bone tissue of rheumatoid arthritis (RA) patients. The expression of CCL20 and of its receptor CCR6 was evaluated in osteoblasts isolated from bone tissue of post-traumatic (PT) patients. Functional tests were performed to evaluate osteoblast proliferation and matrix protein modulation. Immunohistochemical analysis for CCR6, CCL20, and RANKL was performed on bone samples from RA patients. The role of CCL20 was then analyzed in osteoclast differentiation. We found that in basal conditions CCR6, but not its ligand CCL20, was highly expressed by osteoblasts. Functional analysis on osteoblasts showed that CCL20 significantly increased cellular proliferation but did not affect matrix protein expression. Pro-inflammatory cytokines significantly induced the release of CCL20 and RANKL by human osteoblasts but did not modulate CCR6 expression. Increased expression of CCR6, CCL20, and RANKL was confirmed in RA subchondral bone tissue biopsies. We demonstrated that CCL20 was also an earlier inducer of osteoclast differentiation by increasing the number of pre-osteoclasts, thus favoring cell fusion and MMP-9 release. Our results add new insight to the important role of the CCL20/CCR6, RANKL system in the bone tissue of RA. The contemporary action of CCL20 on osteoblasts and osteoclasts involved in the maintenance of bone tissue homeostasis demonstrates the important role of this compartment in the evolution of RA, by showing a clear uncoupling between new bone formation and bone resorption.
17111092 The effect of infliximab on chemokines in patients with rheumatoid arthritis. 2007 Jul Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of lymphocytes, macrophages, and plasma cells into synovial membrane. The chemokines family promotes chemotactic activity in various leukocyte cell types. Chemokines thus play an essential role in the pathological formation of RA. The aim of the present study was to evaluate the influence of infliximab on serum levels of various chemokines. Twenty-four RA patients were involved in this study, which took place between March 2003 and February 2006. Infliximab was administered by intravenous infusion at a dosage of 3 mg/kg. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, at 14 weeks, and at 30 weeks after the initial treatment. To determine whether serum and synovial fluid from RA also contained significant levels of chemokines compared with osteoarthritis patients (OA), GRO-alpha, MIP-1alpha, MIP-1beta and regulated on activation normal T cell expressed and secreted (RANTES) levels of serum and synovial fluid were measured by ELISA in 20 RA patients and 20 OA patients. GRO-alpha, MIP-1beta, and RANTES levels were significantly higher in RA compared with normal volunteers, while MIP-1alpha levels showed no significant differences. The mean GRO-alpha levels in serum from RA patients treated with infliximab decreased significantly after the initial treatment. The mean RANTES and MIP-1beta levels did not change significantly after the treatment. Infliximab treatment significantly lowered the serum GRO-alpha levels of RA patients. GRO-alpha is one of the crucial cytokines affected by infliximab treatment. The blocking therapy of RANTES and MIP-1beta combined with infliximab treatment may have an additional effect without competition in the TNFalpha cascade.
18240258 The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients 2008 Feb 15 OBJECTIVE: To compare the 1-year retention rates of anti-tumor necrosis factor alpha (anti-TNFalpha) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status. METHODS: Our analyses comprised 847, 172, and 249 anti-TNFalpha treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health-related quality of life (HRQOL) were compared among the groups. RESULTS: Unadjusted 1-year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53-1.07) for PsA versus RA and 0.66 (95% CI 0.47-0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA. CONCLUSION: Our results suggest that survival of anti-TNFalpha treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.
17503665 Assessing theoretical risk and benefit suggested by genetic association studies of CCR5: e 2007 The proliferation of published gene association studies of the CCR5delta32 mutation is of relevance to drug development of a CCR5 antagonist for HIV, in highlighting potential safety concerns. We conducted an initial review of all non-HIV gene association studies of CCR5-delta32, followed by detailed meta-analyses in the three disease areas most commonly reported. Our review indicated no consistent evidence of increased risk of susceptibility to hepatitis C virus infection or multiple sclerosis among individuals with CCR5-delta32 mutation, and suggested treatment with a CCR5 inhibitor is unlikely to have related adverse effects. There was, however, evidence to suggest rheumatoid arthritis as a potential therapeutic target for a CCR5 antagonist. Clinical evidence would be required to confirm these findings.
18276743 Abundant expression of the interleukin (IL)23 subunit p19, but low levels of bioactive IL2 2009 Jan OBJECTIVE: Interleukin (IL)23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL17-producing T helper (Th)17 cells. However, previous studies on IL23 expression in human tissues were based on the p19 subunit only. We aimed to study the expression and regulation of IL23 subunits p19 and p40 in RA compared to patients with osteoarthritis (OA). METHODS: The expression of p19 and p40 in synovial tissues was analysed by in situ hybridisation and immunohistochemistry. IL23 in RA and OA synovial fluids and sera was determined by ELISA. Toll-like receptor (TLR)-dependent induction of p19, p40 and bioactive IL23 was determined in RA synovial fibroblasts (RASF), monocytes and monocyte-derived dendritic cells (MDDCs) by real-time PCR and reverse transcriptase (RT)-PCR, Western blot and functional assays. RESULTS: The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL23 was detected at these sites. Correspondingly, soluble IL23 was not detectable or found at very low levels in synovial fluids and sera of patients with RA. By in vitro experiments, we confirmed that TLR-activated RASF expressed p19 but not p40, in contrast to monocytes, which produced IL23 following TLR stimulation. CONCLUSION: The TLR-dependent induction of p19 but not p40 in RASF and the abundant expression of p19 along with the low or undetectable levels of IL23 in patients with RA provides strong evidence that p19 does not necessarily indicate the presence of IL23, as has been proposed to date.
17384178 Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features 2007 Jun OBJECTIVE: To determine the genetic, clinical and serological characteristics of systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome. METHODS: Clinical manifestations and immunolaboratory features of 22 SSc-RA patients were assessed. The HLA-DR genotype of the 22 SSc-RA patients determined by SSP-PCR was compared with that of 38 SSc patients, 100 RA patients and 50 healthy controls. RESULTS: All overlap patients fulfilled the American College of Rheumatology (ACR) criteria for SSc and RA. Five of the 22 patients (23%) had diffuse cutaneous SSc (dcSSc) and 17 patients (77%) had limited cutaneous SSc (lcSSc). Antinuclear antibody, anti-Scl70, IgM rheumatoid factor and anti-CCP antibody positivity were detected in 22 (100%), 5 (23%), 16 (73%) and 18 patients (82%), respectively. Seventeen patients (77%) had pulmonary fibrosis, 12 (55%) had oesophageal dismotility, 11 (50%) had cardiac and five (23%) had renal involvement. Hand joint destruction was observed in 18 patients (82%). Significantly increased frequencies of HLA-DR3 (36% vs 5%), HLA-DR7 (9% vs 4%), HLA-DR11 (36% vs 7%) and HLA-DRw53 (23% vs 5%) were observed in SSc-RA compared with RA patients (P < 0.05). Allele frequencies of the 'shared epitope' (HLA-DR1 and -DR4) were significantly increased in SSc-RA (32% and 27%, respectively) and RA patients (46% and 31%, respectively) in comparison with SSc patients (10.5% and 16%, respectively) or healthy controls (16% and 14%, respectively) (P < 0.05). CONCLUSIONS: To date this is the largest SSc-RA overlap cohort. Genetics, clinical and immunolaboratory features suggest a mixed phenotype. Our data suggest that SSc-RA overlap syndrome may be a distinct genetic, immunological and clinical entity.