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ID PMID Title PublicationDate abstract
23155223 Meta-analysis suggests that intensive non-biological combination therapy with step-down pr 2013 Mar BACKGROUND/OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage ('disconnect'): patients who have little or no response of disease activity still show reductions in damage progression. In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine with step-down prednisolone) has been shown to be equivalent to high-dose methotrexate and infliximab in suppressing damage progression (BeSt trial). We investigated whether COBRA treatment can also 'disconnect' disease activity and damage. DESIGN: A meta-analysis combined data from the COBRA trial (COBRA vs sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs sequential monotherapy). Linear regression related 1-year progression of damage (Sharp van der Heijde score) as a dependent variable with disease activity (time-averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of a disconnect) as independent variables. The main outcome was the pooled interaction term. RESULTS: Complete data from 60-100% of patients were available. Before pooling, disease activity was the only (strongly) significant independent factor related to damage progression. The pooled interaction term was (weakly) significant: time-averaged DAS44×treatment interaction, one-sided p=0.027; time-averaged CRP×treatment interaction, one-sided p=0.044. CONCLUSIONS: Changes in the relationship between disease activity and damage progression may not be limited to anti-TNF treatment, but a property of early, rapid and deep suppression of joint inflammation, also induced by conventional strategies that include glucocorticoids.
22203215 Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid ar 2012 Apr INTRODUCTION: A protein analysis using mass spectrometry revealed the existence of serum proteins with significant quantitative changes after the administration of infliximab. Among these proteins, regenerating gene (REG) 1α appears to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, the present study was conducted to examine the mechanism of REG1α in RA disease progression. METHODS: Serum samples were collected from RA patients and normal healthy controls. REG1α expression was evaluated by ELISA, RT-PCR, and indirect immunofluorescence microscopy. The functions of REG1α on synovial fibroblasts with regard to apoptosis, receptor activator of NF-κB ligand (RANKL) expression, and cellar proliferation were evaluated using siRNA to inhibit the intrinsic REG1α mRNA expression. RESULTS: The serum concentrations of REG1α in RA patients were higher than in normal healthy controls. The high expression of REG1α was also observed in the synovial tissue of RA patients compared to those of osteoarthropathy patients. In addition, tumor necrosis factor-α (TNF-α) upregulated REG1α expression in the synovial fibroblasts cell line (MH7A). Inhibition of REG1α expression suppressed the induction of RANKL expression by TNF-α. Furthermore, exogenous recombinant REG1α protein inhibited apoptosis and promoted cell proliferation in MH7A cells. These effects were abolished in the REG1α-siRNA MH7A cells. CONCLUSION: The present data suggest that TNF-α induces aberrant REG1α expression and that REG1α plays an important role in aberrant cell proliferation and RANKL expression of synovial fibroblasts, ultimately resulting in pannus formation. Restoration of normal physiological REG1α expression may contribute to disease amelioration.
22971883 Physical activity in rheumatoid arthritis: a systematic review. 2012 Sep BACKGROUND: Physical activity is associated with improved health outcomes in many populations. It is assumed that physical activity levels in the rheumatoid arthritis (RA) population may be reduced as a result of symptoms of the disease. The objective of this review is to establish the current evidence base for levels of physical activity in the RA population. METHODS: A systematic review was performed of 7 databases (Emabase, MEDLINE, AMED, Biomedical Reference Collection Expanded, CINAHL, Nursing and Allied Health Collection, and SportsDiscus) up to February 2011 to examine the evidence in the area. RESULTS: One hundred and thirty-six studies were identified through electronic searching. One hundred and six were excluded based on title and/or abstract analysis and a further 14 were excluded based on full text analysis. Sixteen studies meeting the criteria were deemed suitable for inclusion. The results of the included studies indicate that the level of physical activity may be lower among individuals with RA when compared with healthy controls or normative data. CONCLUSIONS: There are a number of methodological considerations at play within the studies reviewed which prohibits definitive conclusion on the physical activity levels of this population group. Given the known health benefits of physical activity, further research in this area appears indicated.
21373797 Anti-tumor necrosis factor therapy in rheumatoid arthritis patients with a history of deep 2011 Oct Four rheumatoid arthritis patients (three women and one man) who had a history of prosthetic joint infection were treated with anti-tumor necrosis factor (TNF) agents after treatment of the infection. The anti-TNF therapy was subsequently discontinued in three patients. The reason for discontinuation was not the reactivation of infection, but disseminated tuberculosis, Pneumocystis jiroveci pneumonia, and interstitial pneumonia, respectively. These cases suggest that a history of prosthetic joint infection may be a contraindication for treatment with anti-TNF agents.
22410241 Feasibility of a standardized ultrasound examination in patients with rheumatoid arthritis 2012 Mar 12 BACKGROUND: Quality improvement is important to facilitate valid patient outcomes. Standardized examination procedures may improve the validity of US.The aim of this study was to investigate the learning progress for rheumatologists during training of US examination of the hand in patients with rheumatoid arthritis (RA). METHODS: Rheumatologists with varying degrees of experience in US were instructed by skilled tutors. The program consisted of two days with hands-on training followed by personal US examinations performed in their individual clinics. Examinations were sent to the tutors for quality control. The US examinations were evaluated according to a scoring sheet containing 144 items. An acceptable examination was defined as > 80% correct scores. RESULTS: Thirteen rheumatologists participated in the study. They included a total of 104 patients with RA. Only few of the initial examinations were scored below 80%, and as experience increased, the scores improved (p = 0.0004). A few participants displayed decreasing scores.The mean time spent performing the standardized examination procedure decreased from 34 min to less than 10 minutes (p = 0.0001). CONCLUSION: With systematic hands-on training, a rheumatologist can achieve a high level of proficiency in the conduction of US examinations of the joints of the hand in patients with RA. With experience, examination time decreases, while the level of correctness is maintained. The results indicate that US may be applied as a valid measurement tool suitable for clinical practice and in both single- and multi-centre trials.
22354636 Perioperative complications in elective surgery in patients with rheumatoid arthritis trea 2012 Nov We retrospectively investigated the influence of biological agents on delayed wound healing and the occurrence of postoperative surgical site infection (SSI) in patients after surgery for rheumatoid arthritis. The patients were divided into two groups-those with and without treatment with biological agents (276 and 278 joints, respectively)-and adverse events (delay in wound healing and SSI) were investigated. Wound healing was delayed in 11.4% of total knee arthroplasty (TKA) operations, 16.7% of total ankle arthroplasty operations, and 9.7% of foot surgeries in the treatment group, and in 5.5% of TKA operations, 12.5% of total elbow arthroplasty operations, and 5.7% of foot surgeries in the non-treatment group. The difference in the incidence of delayed wound healing between the two groups was not statistically significant. In the treatment group, postoperative superficial and deep infection developed in one and two joints, respectively. In the non-treatment group, superficial infection developed in one joint. There was no statistically significant difference between the two groups. These findings suggest that the use of biological agents may not affect the incidence of postoperative adverse events related to wound healing and SSI.
21777909 Association of tumor necrosis factor alpha and its receptor polymorphisms with rheumatoid 2011 Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with altered expression of pro-inflammatory cytokines. We aim to elucidate the association between the -308G/A polymorphism of the TNF-α gene and 196M/R polymorphism in TNFRII gene and susceptibility and severity of RA. One hundred and seventy-two RA patients and one hundred and sixty controls were enrolled in the study. Polymorphisms (SNPs) at position -308 of TNF and -196 of TNFRII genes were determined using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). TNF AA genotype was more prevalent among the patients. GG genotype was significantly more likely to have erosive arthropathy. TNFRII RR genotype was more prevalent among the patients. Our findings suggest that the 308AA genotype of TNF-α and TNFRII 196M/R polymorphism are associated with RA susceptibility. While only the 308GG genotype of TNF-α is associated with RA severity.
21221686 A case of antisynthetase syndrome in a rheumatoid arthritis patient with anti-PL-12 antibo 2011 Mar In our earlier study, we had reported the case of a patient with rheumatoid arthritis (RA), who had anti-Jo-1 antibodies. This patient had received etanercept (ETN) therapy for RA, after which she had developed overt polymyositis (PM). Although various autoimmune phenomena, including lupus-like diseases, vasculitides, or psoriatic skin lesions, are associated with antitumor necrosis factor (TNF) therapy, the development of PM/dermatomyositis (DM) or antisynthetase syndrome following anti-TNF therapy is extremely rare. Here, we report a case of an RA patient with anti-PL-12 antibodies, who received ETN therapy and subsequently developed the antisynthetase syndrome. She recovered when ETN therapy was withdrawn and high-dose corticosteroid was administered. To date, there have been only five reported cases of RA patients with anti-Jo-1 antibodies who developed overt PM/DM following anti-TNF therapy and only one case of antisynthetase syndrome in an RA patient with anti-PL-7 antibodies. Our patients and the abovementioned reports strongly suggest that onset of overt PM/DM or antisynthetase syndrome in RA patients with anti-aminoacyl tRNA synthetase antibodies is associated with anti-TNF therapy.
22942334 Pain pharmacotherapy in patients with inflammatory arthritis and concurrent cardiovascular 2012 Sep BACKGROUND: Pain in inflammatory arthritis (IA) is common and often multifactorial, and many different pharmacotherapeutic agents are routinely used for pain management. There are concerns that some current pain pharmacotherapies may increase the risk of adverse events in patients with concurrent cardiovascular (CV) or renal disease. METHODS: A systematic literature review was performed searching Medline, Embase, Cochrane Central Register of Controlled Trials, DARE, and Cochrane Database of Systematic Reviews. We also hand-searched conference proceedings for the American College of Rheumatology and the European League Against Rheumatism for 2008-2009. RESULTS: Our search identified 4782 studies, of which 190 were included for detailed review, but none met the inclusion criteria for our review. We identified 1 study of etoricoxib and diclofenac in non-IA populations [osteoarthritis (OA) or mixed OA and rheumatoid arthritis]. In that study, the presence of CV disease increased the likelihood of a further CV event 3-fold. Patients with 2 or more CV risk factors showed a 2-fold increased likelihood of adverse CV events. CONCLUSION: Our review has highlighted a lack of specific evidence to guide clinicians in the management of pain in patients with IA and coexistent CV or renal disease. In the absence of this evidence, we suggest clinicians use nonsteroidal antiinflammatory drugs (NSAID) with caution in patients with preexisting CV disease or ≥ 2 CV risk factors. There is currently no evidence to advise clinicians considering other pain pharmacotherapies in the context of CV comorbidities. Current guidelines regarding the use of NSAID and opioids in moderate to severe renal impairment should also be applied to the IA population.
21484222 Fracture risk assessment and osteoporosis treatment disparities in 3,970 Japanese patients 2011 Aug The aims of this study are to determine the proportion of patients at high risk for major osteoporotic and hip fractures in a Japanese cohort with rheumatoid arthritis (RA) and to determine if a care gap exists for high-risk patients. The Fracture Risk Assessment Tool (FRAX®) was administered to 3,970 Japanese patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis cohort study with (n=276) and without (n=3,694) the use of bone mineral density (BMD) measurement. The study population had a mean age of 62 years and was 84% female. Among the 1,522 patients ≥65 years of age, 661 (43%) and 1,304 (86%) were at high risk for a major osteoporotic fracture (10-year probability >20%) and hip fracture (>3%), respectively. Among patients at high risk for a major osteoporotic fracture (n=723), only 453 (63%) and 320 (44%) reported taking any osteoporosis medications and bisphosphonates, respectively. Among female patients with BMD measurements (n=262), the 10-year risk of a major osteoporotic fracture calculated with BMD was significantly higher than in those without BMD measurements (P<0.001). The FRAX identified a substantial proportion of elderly Japanese RA patients with a high risk of fractures. A substantial gap exists between fracture risk and osteoporosis treatment in Japanese RA patients, as previously reported for patients of other ethnicities. In addition, the gap may be underestimated when BMD measurements are not involved in the fracture risk assessment.
21885491 Abatacept plus methotrexate provides incremental clinical benefits versus methotrexate alo 2011 Nov OBJECTIVE: This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase. METHODS: Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit. RESULTS: Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups. CONCLUSION: More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.
22029666 Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular patholog 2011 Oct 27 BACKGROUND: Evidence suggests that rheumatoid arthritis (RA) may enhance or reduce the progression of Alzheimer's disease (AD). The present study was performed to directly explore the effects of collagen-induced rheumatoid arthritis (CIA) on amyloid plaque formation, microglial activation, and microvascular pathology in the cortex and hippocampus of the double transgenic APP/PS1 mouse model for AD. Wild-type or APP/PS1 mice that received type II collagen (CII) in complete Freund's adjuvant (CFA) at 2 months of age revealed characteristics of RA, such as joint swelling, synovitis, and cartilage and bone degradation 4 months later. Joint pathology was accompanied by sustained induction of IL-1β and TNF-α in plasma over 4 weeks after administration of CII in CFA. RESULTS: CIA reduced levels of soluble and insoluble amyloid beta (Aβ) peptides and amyloid plaque formation in the cortex and hippocampus of APP/PS1 mice, which correlated with increased blood brain barrier disruption, Iba-1-positive microglia, and CD45-positive microglia/macrophages. In contrast, CIA reduced vessel density and length with features of microvascular pathology, including vascular segments, thinner vessels, and atrophic string vessels. CONCLUSIONS: The present findings suggest that RA may exert beneficial effects against Aβ burden and harmful effects on microvascular pathology in AD.
23087178 Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low 2013 Jun OBJECTIVE: Early diagnosis of rheumatoid arthritis (RA) remains a challenge. Interleukin (IL)-7 is a pleiotropic cytokine that plays a central role in the development and maintenance of T-cells and has been associated with T-cell dysfunction in RA. Serum levels of IL-7 are reduced in both early and established disease. The aim of this study was to determine whether serum IL-7 can identify patients with very early inflammatory joint symptoms who will progress to RA, and to examine whether IL-7 levels predict disease persistence and radiographic progression. METHODS: Patients with inflammatory joint symptoms<6 months followed over 5 years for progression to RA and 80 healthy controls were studied. Baseline IL-7 levels were measured by ELISA. RESULTS: Of 250 patients, 108 developed RA (ACR 1987- criteria). IL-7 at inclusion was reduced significantly in RA compared with non-RA patients (p=0.009). IL-7 was categorised using the lower limit of the healthy control distribution (10 pg/ml). In multivariate analysis, independent predictors of RA development were: antibodies against citrullinated peptides (ACPA) positivity (p=0.001), IL-7<10 pg/ml (p=0.003) and swollen joint count (p=0.050). In the ACPA-negative subgroup (n=199), the only predictors were: DAS-44 (p=0.001), IL-7<10 pg/ml (p=0.010) and radiographic erosions (p=0.050). At 1-year follow-up, remission (DAS<1.6) was only predicted by ACPA negativity (p=0.019) and IL-7>17 pg/ml at recruitment (p=0.013). CONCLUSION: These data demonstrate that low IL-7 levels in patients with recent onset of symptoms may have value as a diagnostic biomarker predicting the progression to RA, particularly in ACPA-negative disease, as well as being related to RA progression.
22613658 Association between the eNOS gene polymorphisms and rheumatoid arthritis risk in a norther 2012 Apr BACKGROUND: Several genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene are associated with the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to investigate whether the two SNPs (T-786C and G894T) of the eNOS gene are associated with rheumatoid arthritis risk in a northern Chinese population. METHODS: In this study, the eNOS genes T-786C and G894T were studied in 196 cases with rheumatoid arthritis and 201 healthy controls with gender, age and ethnicity matched. The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The analyses of association were statistically compared using the chi-square test with SPSS software for Windows. RESULTS: The frequency of the -786C allele was significantly higher in the rheumatoid arthritis patients than in the healthy controls (19.64% vs. 14.18%, P < 0.05). However, the 894T allele of the eNOS gene was not increased in the rheumatoid arthritis patients compared to the healthy controls. CONCLUSIONS: Individuals with the -786CC genotype have an increased risk of rheumatoid arthritis. Further study with an increased sample size is necessary for the study of the role of this SNP in rheumatoid arthritis.
21305500 Mechanisms and clinical relevance of TRAIL-triggered responses in the synovial fibroblasts 2011 Apr OBJECTIVE: Results of studies in mice suggest a protective role for TRAIL in arthritis. The aim of this study was to investigate the role of TRAIL in patients with rheumatoid arthritis (RA). METHODS: In the present study, we compared RA fibroblast-like synoviocytes (FLS) that were resistant or sensitive to TRAIL-induced apoptosis and the expression of TRAIL receptors in these cells, and also investigated the clinical features of the patients from whom the FLS were derived. Furthermore, we evaluated the levels of TRAIL and its soluble decoy receptor osteoprotegerin (OPG) in patients with RA, patients with osteoarthritis (OA), and patients with spondylarthritis (SpA). RESULTS: Sensitivity to TRAIL-induced apoptosis varied in FLS from different patients, and the severity of disease in patients with RA was inversely correlated with the susceptibility of their FLS to TRAIL-induced apoptosis. TRAIL-sensitive cells expressed significantly lower levels of TRAILR-1, and silencing of TRAILR-1 increased TRAIL-induced apoptosis in RA FLS. TRAIL levels were elevated in the arthritic joints of patients with established RA, and TRAIL levels in the synovial fluid of these patients were elevated compared with levels in the synovial fluid of patients with OA or SpA. At baseline, a low OPG-to-TRAIL ratio in the sera of patients with early RA was associated with a better evolution of disease activity, but high serum levels of TRAIL at followup were associated with joint damage. CONCLUSION: These findings suggest that TRAIL has a dual role in RA, and that the resistance of RA FLS to TRAIL-induced apoptosis is associated with a disease-promoting activity of TRAIL in RA.
21178849 Progression of cervical spine instabilities in rheumatoid arthritis: a prospective cohort 2011 Apr 15 STUDY DESIGN: A 5-year prospective cohort study of cervical spine instabilities in rheumatoid arthritis (RA). OBJECTIVE.: To clarify the natural course of cervical instabilities in RA patients and to determine predictors for the prognosis of RA cervical spine. SUMMARY OF BACKGROUND DATA: Although several previous studies investigating the natural history of RA cervical spine have been reported, few of them have described radiological predictive factors for the aggravation of these instabilities. METHODS: Two hundred sixty-seven outpatients with "definite" or "classical" RA initially assigned were prospectively followed for over 5 years. Radiographic cervical findings were classified into three representative instabilities: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). The aggravations of these instabilities were identified in the cases with a decrease of at least 2 mm in the Ranawat value of VS, an increase of at least 1 mm in translation of SAS, or a new development of respective instabilities. RA stages and mutilating changes were assessed in the hand radiograms. RESULTS: Fifty-two point four percent of 267 patients, without any cervical instability at the beginning of follow-up, decreased to 29.6% at the end (P < 0.01), whereas VS and SAS increased significantly (P < 0.01). The aggravation of VS was observed at statistically higher rates in patients with pre-existing instabilities as follows; 25.7% of AAS (P = 0.01), 49.1% of VS (P < 0.01), and 41.2% of SAS (P = 0.06). The aggravation of SAS was also detected in 47.2% of VS and 64.7% of SAS (P < 0.01). Patients with pre-existing mutilating changes exhibited the aggravations of VS and SAS in significantly higher incidences (P < 0.01). Furthermore, the cases with development into mutilating changes during the follow-up showed significantly higher tendencies for the aggravations of these instabilities (P < 0.01). CONCLUSION: The incidences of VS and SAS significantly increased during the minimum 5-year follow-up. Prognostic factors of these instabilities were revealed to be the initial radiological findings of VS, SAS, and mutilating changes.
22265066 Cost of illness and quality of life of patients with rheumatoid arthritis in South Korea. 2012 Jan OBJECTIVE: To estimate the cost of illness (COI) and health-related quality of life (HRQOL) of rheumatoid arthritis (RA) according to four different levels of functional severity. METHODS: A face-to-face interview survey was administered to patients with RA recruited at the Rheumatology Clinic of Seoul National University Hospital. Direct costs (medical costs [treatment, drug, private physiotherapy, traditional Chinese medicine, other alternative medicine], nonmedical costs [travel, dietary supplements, auxiliary device, home assistance]), indirect costs (productivity loss due to job loss and sick leave), and deterioration in the HRQOL of patients with RA were measured. Factors associated with the COI and the HRQOL were analyzed by using multiple regression and multivariate logistic regression. RESULTS: A total of 196 patients were enrolled for this study. As RA functional severity worsened, the total costs increased accordingly (class I: 4,230,204 Korean won, class II: 7,250,674 Korean won, class III: 8,046,434 Korean won, class IV: 8,206,215 Korean won). Direct costs also increased with the severity of the functional status, with a sharp decrease in class IV. The average HRQOL score was 0.49, showing an evident impact of RA severity (class I: 0.67, class II: 0.50, class III: 0.29, class IV: 0.23). Functional class and comorbidity were significant determinants of the COI and the HRQOL. CONCLUSION: Functional severity was a major factor associated with higher COI and lower HRQOL scores. Therefore, preventing the aggravation of functional severity is crucial for decreasing the COI and improving the HRQOL of patients with RA.
22059990 The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a majo 2011 Dec Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. For this purpose we genotyped single nucleotide polymorphisms (SNPs) in a Dutch set of RA patients and controls. Similarly, a meta-analysis using a Spanish cohort of RA as well as six large genome-wide association studies (GWAS) studies was performed. For these SNPs we analysed more than 6000 patients and 20,000 controls. The CFH variants, I62V, Y402H, IVS1 and IVS10, known to associate strongly with AMD, did not show a significant association with the risk of developing RA despite a strong statistical power to detect such differences. In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA.
21677005 Effect of the application of trial inclusion criteria on the efficacy of adalimumab therap 2011 Sep OBJECTIVE: To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response. METHODS: The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy. RESULTS: Thirteen trials (n = 54-799) with 11 different sets of entry criteria were identified, resulting in 11 projection groups (n = 22-168). The DAS28 at baseline was similar in the original trial and each projection group based on this trial (5.1-6.4, total AdRA cohort 5.1). After 28 weeks, the efficacy varied substantially among the 11 projected groups (change from baseline DAS28: -1.65 to -2.65, time-averaged DAS28 3.67-4.53). Expressed as outcome (DAS28 at 28 weeks), the efficacy was much more similar for almost all projection groups (3.5-4.0) and thus appeared to be mostly independent of disease activity at baseline. CONCLUSION: We observed that different inclusion criteria for clinical trials can have a marked effect on the expected response, i.e., improvement from baseline. A novel finding is that final disease activity appeared much less dependent on initial disease activity. Our study suggests that for daily practice, one can assume that adalimumab treatment will on average result in a DAS28 between 3.5 and 4.0 after 28 weeks of treatment, regardless of baseline disease activity.
21528424 Past hepatitis B virus infection in rheumatoid arthritis patients receiving biological and 2011 Dec To evaluate the prevalence of past infection with hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) and the incidence of its reactivation under treatment with biological and/or nonbiological disease-modifying antirheumatic drugs (DMARDs), 239 patients receiving DMARD therapy were consecutively enrolled and tested for HBV-DNA, using a real-time polymerase chain reaction assay, HBV serology including hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), and serum levels of aminotransferase. Data prior to DMARD therapy and during follow-up were examined by reviewing medical records. Two patients (0.8%) were positive for HBsAg at the start of therapy. Sixty patients (25.1%) showed HBsAg-negative and anti-HBc-positive serology indicative of past HBV infection. Among these 60 patients, 2 patients (3.3%) experienced reactivation of viral replication (<2.1 log copies/ml) during DMARD therapy. One had been receiving tacrolimus, prednisolone, and methotrexate (MTX); the other had been treated with adalimumab, prednisolone, and MTX. Their serum aminotransferase levels remained normal, and HBsAg was negative. Ten weeks after reactivation of viral replication had been noted, the HBV-DNA titer in the former patient had increased to 2.9 log copies/ml, and HBsAg and hepatitis B e antigen had become weakly positive. In contrast, the latter patient had become negative for viral DNA without any antiviral prophylaxis. In conclusion, the use of biological and nonbiological DMARDs is relatively safe in most RA patients with past HBV infection, even when no anti-HBV prophylaxis is administered. Considering the high prevalence of past infection in RA patients and the high cost of prophylaxis against HBV reactivation, universal prophylaxis is impractical. Regular monitoring of serum viral DNA seems to be the most rational approach to preventing the development of clinically apparent hepatitis.