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ID PMID Title PublicationDate abstract
23193984 Raised circulating tenascin-C in rheumatoid arthritis. 2012 Nov 29 INTRODUCTION: The aim of this study was to examine whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TNC) are elevated in musculoskeletal disorders including rheumatoid arthritis (RA) and to assess in RA whether levels are related to clinical disease status and/or patient response to treatment. METHODS: TNC in serum or plasma was quantified by ELISA. Samples from 4 cohorts of RA patients were examined and compared to normal human subjects and to patients with other inflammatory diseases. RESULTS: Circulating TNC levels were significantly raised in patients with RA, as well as patients with systemic lupus erythematosus, idiopathic inflammatory myositis, psoriatic arthritis and ankylosing spondylitis, whilst patients with Sjogren's syndrome displayed levels similar to healthy controls. The highest levels of TNC were observed in RA patients with late stage disease. In early disease TNC levels correlated positively with ultrasound determined erosion scores. Treatment of early RA patients with infliximab plus methotrexate (MTX) resulted in a transient decrease in circulating TNC over the first year of therapy. In contrast, TNC levels increased over time in RA patients receiving MTX alone. In patients treated with infliximab plus MTX, baseline TNC levels significantly correlated with tender joint counts (TJC) at 18 and 54 weeks after initiation of infliximab therapy. CONCLUSIONS: Raised circulating TNC levels are detected in specific inflammatory diseases. Levels are especially high in RA where they may act as a biomarker of bone erosion and a predictor of the effect of infliximab on RA patient joint pain.
22505698 Indirect treatment comparison of abatacept with methotrexate versus other biologic agents 2012 Jun OBJECTIVE: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom. METHODS: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL). RESULTS: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months. CONCLUSION: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.
22507346 Can the association of Ciclosporine A and Methotrexate maintain remission/low disease acti 2012 Jan The opportunity to induce remission/low disease activity in Rheumatoid Arthritis (RA) patients has been achieved in recent years by the adoption of more sensitive diagnostic methods [Magnetic Resonance Imaging (MRI), ultrasonography] and early aggressive treatments (combination of biologics and synthetic DMARDs). On the other hand, data are still scarce and contrasting about the management of long-term remission. The aim of this preliminary study is to evaluate whether the association of Methotrexate + Ciclosporine A (MTX + CSA) therapy in early RA (eRA) patients is able to maintain remission/low disease activity and avoid structural progression, evaluated by MRI. Etanercept was suspended in patients who reached remission/low disease activity and CSA+MTX therapy was introduced (T0), all patients continued to receive MTX; at this time MRI showed mild/moderate synovitis and erosions in all the patients; 1-year after (T1), a slight reduction in mean synovitis, bone edema and total score was observed, whereas the erosion score was unchanged. The mean DAS44 remained stable from T0 to T1 and 6/7 patients maintained a low disease activity score. No side effects were reported. These results confirm the good clinical efficacy and safety of the combination therapy CSA+MTX in eRA patients and demonstrate a parallel arrest of structural damage evaluated by MRI 1-year after etanercept suspension.
21497534 Remission in early rheumatoid arthritis treated with conventional DMARDs. Results of a two 2012 Jan OBJECTIVE: This study aimed to evaluate remission in patients with early RA treated by conventional DMARDs and to identify its possible predictor factors. METHODS: Patients with early RA (<12 months) were enrolled in a 2-year follow-up study. Standard evaluation completed at baseline and at 24 months included clinical, laboratory, functional and structural assessment. Clinical remission after 2 years of follow-up was defined when DAS28 was less than 2.6. Possible predictor factors for remission were analyzed. RESULTS: Fifty-one patients (88.2% women, mean age of 46.9 [24-72] years, mean disease duration of 24 [6-48] weeks) were enrolled in this study. The delay in referral for specialist care was 140 [7-420] days. Rheumatoid factor, anti-CCP, HLA-DRB1*01 and DRB1*04 alleles were present respectively in 62.5, 56.6, 11.8, and 45.1% of patients. At 24 months, 77.2% received a median dose of 5 (0-8) mg/day of prednisone and 65.2% was taking methotrexate (MTX). 13.6% of patients had stopped their DMARD because of socioeconomic difficulties. At 24 months, we noted a significant improvement of morning stiffness, pain score, swollen joint count, ESR, CRP, DAS28 and HAQ scores. Remission at 2 years was noted in 34.8% of patients and was significantly associated in univariate but not in multivariate analysis to male sex (P=0.02) and to short delay in referral for specialist (P=0.03). CONCLUSION: In this cohort of early RA patients treated with conventional DMARDs, especially with methotrexate in monotherapy, remission at 2-year of follow-up was obtained in one third of patients. No predictor factors of remission were found out. These results should be verified by further studies.
22073935 Biologic agents in rheumatoid arthritis: an update for managed care professionals. 2011 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis that clinically manifests as joint pain, stiffness, and swelling. If left untreated, persistent synovial inflammation can progress to cartilage and bone destruction and ultimately to major long-term disability and mortality. Synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, leflunomide, and sulfasalazine, have markedly improved clinical symptoms and slowed joint damage in RA patients. However, despite the effectiveness of synthetic DMARDs, many patients who use them continue to have clinical symptoms of inflammation and progressive joint destruction. Recent advances in our understanding of the pathogenesis of RA have led to the identification of novel cellular and molecular therapeutic targets. Biologic agents aimed at these targets have provided some evidence of effectiveness that is transforming the management of RA. OBJECTIVE: To inform health care providers about some of the recent advances in RA pathogenesis and innovative biologic therapies that have shown effectiveness in improving clinical outcomes and inhibiting radiographic progression. SUMMARY: Although the specific trigger of the autoimmune response in RA is not known, pathogenesis is generally believed to be associated with the generation of autoantibodies through interactions of antigen-presenting cells with the adaptive immune system (CD4 + T cells and B cells). The main inflammatory mediators of joint inflammation and destruction in RA are tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), IL-6, chemokines, and proteases. Advances in our understanding of the key cells and inflammatory cytokines have led to the development of targeted biologic agents. As of 2011, 5 TNF-alpha inhibitors are approved for use by the FDA: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol. In randomized clinical trials, all of these agents have been shown to be effective in reducing clinical signs of inflammation in RA patients who have failed synthetic DMARDs. Multiple studies have demonstrated significant benefits of early treatment with TNF-alpha inhibitors combined with methotrexate. Other FDA-approved biologic agents for treating moderate-to-severe RA include abatacept, rituximab, and tocilizumab. All biologic agents carry an increased risk of infections. Additional potential side effects include infusion and injection site reactions for intravenous and subcutaneously administered agents, respectively. All patients being considered for biologic agents should be screened annually for tuberculosis and should receive pneumococcal, influenza, and hepatitis B vaccinations.
22527215 [Drug-drug interactions in antirheumatic treatment]. 2012 Apr Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk.
22098778 Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous 2012 Feb Rheumatoid arthritis (RA) is a systemic autoimmune disease that is initiated and maintained by various inflammatory/immune cells and their cytokines, leading to cartilage degradation and bone erosion. Despite its potent therapeutic efficacy on RA, the oral administration of methotrexate (MTX) provokes serious adverse systemic complications, thus necessitating the local application of MTX. Here, we show that transcutaneous MTX (TC-MTX) can efficiently penetrate joint skin ex vivo and in vivo, and that TC-MTX can significantly improve the various inflammatory symptoms associated with RA. Further, TC-MTX preserved the joint-structures in mice with collagen-induced arthritis (CIA), which was also confirmed by three-dimensional micro-computed tomography scan. TC-MTX markedly decreased the secretion of inflammatory cytokines both in the serum and in inflamed joints of CIA mice. Further, its therapeutic potential is comparable to that of etanercept, a biological agent that block tumor necrosis factor (TNF)-α. Importantly, the systemic cytotoxicity of TC-MTX was not detected. Thus, TC-MTX can be a new therapeutic modality for RA patients without systemic complications.
21528382 Comparison of QuantiFERON-TB Gold and the tuberculin skin test for detecting previous tube 2011 Dec The aim of the study was to compare the usefulness of the QuantiFERON-TB Gold (QFT-2G) with that of the tuberculin skin test (TST) for detecting previous infection of tuberculosis (TB) in Japanese rheumatoid arthritis (RA) patients. Before receiving biologic therapy, 97 RA patients were divided into two groups based on their chest computed tomography (CT) findings: the TB past infection group (n = 48), with old inflammatory changes due to prior pulmonary TB; and the non-TB infection group (n = 49), without such findings. The QFT-2G was not affected by methotrexate or prednisolone. Indeterminate results with a positive control had a low incidence (5.2%). A positive QFT-2G for the TB past infection group at cutoffs of 0.35 and 0.1 IU/ml (intermediate range) was seen in 5.8% and 20.8%, respectively. A TST >20 mm was significantly higher in the non-TB infection group (31%) than in the TB past infection group (13%). The correlation between the QFT-2G and TST was poor among all patients. Disagreement between these tests in the non-TB infection group was caused by the false-positive TST induced by previous Bacillus Calmette-Guérin (BCG) vaccination. Only 12 (12.4%) of 97 patients had a positive QFT-2G (≥0.1 IU/ml) and a negative TST (<20 mm), but in this subgroup, a high incidence (10, 83.3%) was detected in the TB past infection group. QFT-2G may be a good alternative to the TST to evaluate previous TB infection when it is necessary to determine whether isoniazid (INH) prophylaxis is needed before biologic therapy is begun.
21046421 Management of rheumatoid arthritis: consensus recommendations from the Hong Kong Society o 2011 Mar Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy.
22151924 Abatacept with methotrexate versus other biologic agents in treatment of patients with act 2011 INTRODUCTION: The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR). METHODS: A systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI). RESULTS: The analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Abatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.
22364131 Excess cardiovascular risk in inflammatory rheumatic diseases: pathophysiology and targete 2012 The article reviews the evidence and extent of the excess cardiovascular risk in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis. RA entails nearly twice as high a standardized mortality ratio and is considered an equivalent of type 2 diabetes with regard to cardiovascular risk. The associated excess cardiovascular risk can only partly be explained by traditional risk factors, and the underlying inflammation is crucially involved in the pathogenesis. Data obtained from patients with early RA suggest that serum triglycerides, a proxy of disease activity as markers of systemic inflammation, impaired function of apolipoprotein A-I and HDL particles, and mediating hypertension are determinants of the excess cardiovascular risk. These changes seem to be preceded by a lowering of total cholesterol and are followed in the course of the disease by immune processes typically illustrated by positivity of rheumatoid factor. Evidence is available to postulate the notion that reduced plasma lipoprotein- associated phospholipaseA2 mass or activity, mediated by diminished hydrolysis of VLDL triglycerides and of Lp(a) phospholipids, may induce reduction or altered composition of HDL particles and apoA-I dysfunction which, along with elevated plasma triglycerides, initiate and contribute to chronic inflammation. Lifestyle modification, traditional non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors, low-dose corticosteroids, statins, tumor-necrosis-α inhibitors and, particularly, the immunosuppressive methotrexate, all have potential beneficial effects in eliciting a reduction in disease activity and cardiovascular risk. Adherence to the recent EULAR recommendations is a key in the prevention and management of cardiovascular risk among patients with rheumatic diseases.
22764596 [Effect of fire-needle intervention on serum IL-1 and TNF-alpha levels of rheumatoid arthr 2012 Apr OBJECTIVE: To observe the effect of fire-needle intervention on serum IL-1 and TNF-alpha contents in rheumatoid arthritis (RA) rats so as to study its underlying mechanism in improving RA. METHODS: A total of 40 Wistar rats were randomized into normal control, model, methotrexate (MTX, medication) group and fire-needle groups, with 10 cases in each group. RA model was established by injecting Freund's complete adjuvant (0.1 mL) into the rats' right hind paw. Fire-needle was applied to "Jiaji" (EX-B 2),"Zusanli" (ST 36) and "Ashi point" (the most severe site of the swelling joint), once every three days and 8 times altogether. The rat's right hindpaw swelling volume was detected by volumetric method, and serum IL-1 and TNF-alpha contents were determined by double antibody sandwich ELISA. The pathological changes of synovium tissue of the right knee-joint were observed by optical microscope. RESULTS: In comparison with the control group, the swollen paw volumes at time-points of 12 d, 19 d, 26 d and 33 d after modeling and serum IL-1 and TNF-alpha contents were increased significantly (P < 0.01). Compared to the model group, the swollen paw volumes on day 33 in both medication and fire-needle groups were decreased considerably (P < 0.01), while serum IL-1 and TNF-alpha contents in the medication and fire-needle groups were reduced significantly (P < 0.05, P < 0.01). No significant differences were found between the medication and fire-needle groups in the swollen paw volumes on day 12 (P > 0.05). The pathological states (synovial cells' arrangement, inflammatory infiltration, synovial membrane thickening, etc.) of synovium tissue of the right knee-joint in both medication and fire-needle groups were relatively lighter than those of the model group. CONCLUSION: Fire-needle therapy can down-regulate serum IL-1 and TNF-alpha contents in rheumatoid arthritis rats, and reduce the degree of arthroncus of the affected joint, which may contribute to its effect in improving synovial lesions.
20798997 Effects of different medical treatments on serum copper, selenium and zinc levels in patie 2011 Sep The aim of the present study was to measure the changes in serum selenium, zinc, and copper in patients being treated for rheumatoid arthritis. Thirty-two patients and 52 healthy controls were included in the study. The copper level was higher and those of selenium and zinc were lower in the patients relative to controls. Treatment with methotrexate elevated the zinc levels, but not zinc and selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non-steroidal anti-inflammatory drugs did not change the levels of any of the elements studied. The decrease in zinc and selenium levels and elevation in copper levels observed in the patients probably resulted from the defense response of organism and are mediated by inflammatory-like substances.
23234647 Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. 2013 Sep 1 OBJECTIVES: Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA). METHODS: Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12. RESULTS: 55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10 mg, 30 mg, 50 mg, and 100 mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (-0.48 vs -0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed. CONCLUSIONS: Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA.
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.
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.
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.
21372513 A case of Weber-Christian disease with later development of rheumatoid arthritis. 2011 Weber-Christian disease (WCD) is a syndrome characterized by recurrent subcutaneous nodules, fever, occasional lipoatrophy, fatigue, arthralgia, and myalgia. We report a case of WCD associated with rheumatoid arthritis. A 65-year-old woman consulted our outpatient clinic because of bilateral hand swelling. The patient had presented with fever and subcutaneous nodules in her trunk and upper and lower extremities in 1983. At that time, the dermatology department diagnosed this patient as having WCD after biopsy of the nodules demonstrated lobular panniculitis. She has been treated with corticosteroid (5-15 mg/day) since then. The patient continued to have recurrent episodes of transient inflammatory arthritis in the small joints of the fingers and fever, and was initially assessed at our institution in October 2007. Finally, in November 2007, she was diagnosed as having both WCD and rheumatoid arthritis (RA) and treated with corticosteroid (5 mg/day) and methotrexate (MTX) (7.5 mg/week). Thereafter, her clinical symptoms gradually improved. This is the second case of WCD showing the subsequent development of RA, successfully treated with MTX, in the English literature. This case may provide clinical insight into WCD and RA.
21360490 Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequ 2011 Mar OBJECTIVE: To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX. METHODS: A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented. RESULTS: Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events. CONCLUSION: The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile.
22562983 Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate resp 2013 Jan OBJECTIVE: In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy. METHODS: Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage. RESULTS: Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively. CONCLUSION: No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.