Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16219707 Diagnosis and management of adult onset Still's disease. 2006 May BACKGROUND: Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology that is responsible for a significant proportion of cases of fever of unknown origin and can also have serious musculoskeletal sequelae. OBJECTIVE: To assess and synthesise the evidence for optimal diagnosis and management of AOSD. METHODS: The key terms, adult onset Still's disease, AOSD, adult Still's disease, ASD, Still's disease were used to search Medline (1966-2005) and PubMed (1966-2005) for all available articles in the English language. Clinically relevant articles were subsequently selected. Bibliographies, textbooks, and websites of recent rheumatology conferences were also assessed. RESULTS: Data on diagnosis and treatment of AOSD are limited in the medical literature and consist mainly of case reports, small series, and modest scale retrospective studies. Diagnosis is clinical and requires exclusion of infectious, neoplastic, and other autoimmune diseases. Laboratory tests are non-specific and reflect heightened immunological activity. Treatment comprises non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive drugs (methotrexate, leflunomide, gold, azathioprine, cyclosporin A, cyclophosphamide), and intravenous gammaglobulin. The recent successful application of biological agents (anti-tumour necrosis factor, anti-interleukin (IL)1, anti-IL6), often in combination with traditional immunosuppressive drugs, has been very promising. CONCLUSIONS: AOSD often poses a diagnostic and therapeutic challenge and clinical guidelines are lacking. The emergence of validated diagnostic criteria, discovery of better serological markers, and the application of new biological agents may all provide the clinician with significant tools for the diagnosis and management of this complex systemic disorder.
20477085 Leflunomide in the treatment of rheumatoid arthritis. 2006 Jan Rheumatoid arthritis is a chronic and highly morbid disease affecting approximately 1% of the world's population. With the advent of disease-modifying antirheumatic drugs, patients are increasingly able to maintain control of their arthritis and prevent joint destruction. However, not all patients respond adequately to any single disease-modifying antirheumatic drug, and many newer parenteral therapies are cost prohibitive. Leflunomide, an inhibitor of pyrimidine biosynthesis, is the first oral disease-modifying antirheumatic drug to have been approved for rheumatoid arthritis in the USA in the last 15 years, and is now widely used in over 70 countries around the world. Leflunomide is efficacious when used as monotherapy or in combination with methotrexate to treat patients with rheumatoid arthritis, and is generally well tolerated. As clinical use increases, new ways to use leflunomide in order to minimize toxicity and maximize efficacy are being explored.
20477056 Autoantibody production in patients treated with anti-TNF-alpha. 2008 Mar Patients with rheumatoid arthritis, Crohn's disease or spondyloarthritis who are treated with selective TNF-alpha inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-dsDNA antibodies. Various methods have shown that infliximab led to ANAs in 29-76.7% and anti-dsDNA antibodies in 10-29% of rheumatoid arthritis patients participating in clinical trials. Furthermore, ANAs and anti-dsDNA antibodies have appeared in 11-36 and 5-15% of rheumatoid arthritis patients treated with etanercept and 12.9% and 5.3% of those treated with adalimumab, respectively. Antiphospholipid antibodies, which are mainly detected by means of anticardiolipin assays, have also been found in rheumatoid arthritis patients receiving TNF-alpha blockers. There have been a number of reports of the development of antidrug antibodies, of which those against infliximab lead to infusion reactions and shorter responses to treatment. This has led some authors to conclude that it is necessary to add methotrexate to infliximab in order to reduce the risk of the appearance of anti-idiotype autoantibodies.
20476948 Methotrexate in rheumatoid arthritis. 2007 Jan After half a century of use, methotrexate continues to be a cornerstone in the therapy of rheumatoid arthritis. Renewed interest in the 1980s has brought new insights into the mechanisms of action and safety of the drug. The use of combination therapy in rheumatoid arthritis has not masked the value of methotrexate in a competitive market in any way. We review the pharmacodynamics and pharmacokinetics as applicable to its clinical use as an anti-inflammatory and disease-modifying agent here.
18557533 [Adult onset Still's disease]. 2008 Apr 23 Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder affecting mainly young adults. AOSD is characterized clinically by spiking fever, arthritis, evanescent rash, sore throat, enlargement of lymph nodes and splenomegaly, and biologically by neutrophilic leukocytosis, high levels of ferritine and elevated liver enzymes. None of these features are specific, and although several classification criteria have been proposed, AOSD remains a diagnosis by exclusion. Its causes and pathomechanism are still unknown, although there is increasing evidence of dysregulated innate immune response. Treatment mainstays are systemic corticosteroids and methotrexate. Blockade of proinflammatory cytokines may be effective in the substantial proportion of patients with poor response to classical immunosuppressants.
19707430 Review of tocilizumab in the treatment of rheumatoid arthritis. 2008 Mar Constitutively overproduced in proliferating synovial tissues, interleukin-6 (IL-6) is deeply involved in the pathology of rheumatoid arthritis (RA). Tocilizumab is a humanized anti-human IL-6 receptor antibody that binds to soluble and membrane-bound IL-6 receptor, and at detectable levels in blood, tocilizumab is capable of almost completely blocking the transmembrane signaling of IL-6. In clinical trials for patients with RA in Japan, tocilizumab monotherapy has shown clinical efficacy equaling that of tumor necrosis factor (TNF) inhibitor in combination with methotrexate, and in an extension study in patients who responded to tocilizumab, almost no patients showed a decrease in the efficacy of tocilizumab. Evidence obtained in a phase III study in Japan demonstrated that tocilizumab monotherapy had a sig-nificant inhibitory effect on the progression of structural joint damage compared with that of conventional disease modifying antirheumatic drugs (DMARDs). Furthermore it has been shown that tocilizumab has an excellent ability to suppress serum amyloid A levels and could therefore be an important therapeutic strategy in amyloid A amyloidosis secondary to rheumatic diseases. The safety profile of tocilizumab appears to be satisfactory. However, several serious infections were also reported, and careful monitoring is therefore important during use.
29793290 Pharmacogenomics in the treatment of rheumatoid arthritis: clinical implication and perspe 2006 May Rheumatoid arthritis (RA) is a chronic inflammatory disease. The inflammatory process of the joint destroys articular architecture and causes a significant disability. The efficacy of disease modifying antirheumatic drugs such as methotrexate, sulfasalazine and biological response modifiers, is widely accepted. However, the outcome of the treatment with these agents is known to vary among patients. The application of the pharmacogenomics is expected to reduce toxicities and enhance the desirable effects of therapeutic agents for RA. Recently, pharmacogenomic studies on methotrexate, sulfasalazine and tumor necrosis factor-α inhibitors have been reported. These investigations suggest that the pharmacogenomic approach is useful for the treatment of RA, although there are points to be considered before the translation of the pharmacogenomic data into clinical practice. This review focuses on the latest information on the pharmacogenomics of antirheumatic drugs and its clinical implication in the treatment of RA.
16997789 Design of a new line in treatment of experimental rheumatoid arthritis by artesunate. 2006 This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.
18523733 Clinical pharmacology of gold. 2008 Jun Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.
23393485 Payers Have Biologic Alternative for Patients With Moderate to Severe Rheumatoid Arthritis 2006 Dec Earlier biologic therapies for rheumatoid arthritis represented a breakthrough in treatment of the disease, but there are still some patients who do not respond adequately to them. The market entry of abatacept, which allows for consistent dosing and predictable drug-acquisition costs, presents patients, physicians, and third-party payers with an effective alternative - the first therapy proven to be effective in patients with inadequate response to DMARDs such as methotrexate or anti-TNF-alpha therapies.
24692770 Abatacept for the treatment of rheumatoid arthritis: A review. 2007 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs. OBJECTIVES: The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium. METHODS: The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000-September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations. RESULTS: The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%-4.2%) of discontinuation due to adverse events. CONCLUSION: The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.
18360618 Etanercept in the treatment of rheumatoid arthritis. 2007 Mar Etanercept (ETN) is the first anti-tumor necrosis factor (TNF) agent to be approved for the treatment of rheumatoid arthritis (RA). Over the last 8 years, several clinical trials have shown its efficacy and safety in established and early RA, as well as a monotherapy or in combination with methotrexate. ETN not only reduces the signs and symptoms of RA, but also retards the progression of radiographic damage and improves the quality of life and function of patients. Its safety profile has been predictable since the first clinical trials with no new major safety concerns. Beyond its efficacy in RA, ETN is also indicated for the treatment of psoriatic arthritis. This current report reviews the evidence and the data in RA and psoriatic arthritis (PsA).
18473014 A systematic review of infliximab in the treatment of early rheumatoid arthritis. 2007 Oct BACKGROUND: Several health authorities have recently revised the indication of infliximab (IFX) to include the treatment of early rheumatoid arthritis (RA). The aim of this systematic review of the literature was to appraise the efficacy, safety, and cost-effectiveness of early therapy with IFX. METHODS: We identified published clinical trials from 1966 to May 2006. We included randomized clinical trials (RCTs) in RA with disease duration of less than 3 years comparing the treatment of methotrexate-IFX (MTX-IFX) with methotrexate-placebo (MTX-placebo). RESULTS: A total of 8 studies met inclusion criteria. Three studies reported redundant data regarding the vdH Sharp Score. Out of the 5 remaining studies, 4 analyzed structural joint destruction (vdH Sharp Score) and demonstrated a significant reduction in radiographic damage progression in favor of the combination of MTX-IFX compared with MTX-placebo (-4.1 vdH Sharp Score units (95% CI: 3.5; 4.6). Three studies also displayed a benefit of MTX-IFX on functional outcomes of RA (HAQ score) and disease activity measures (DAS, ACR response criteria), although less markedly. CONCLUSIONS: Although data might be skewed because of only 2 existing large studies with concordant data, results from RCTs demonstrate improved efficacy of the combination MTX-IFX compared with MTX-placebo in early RA. However, many early RA patients probably do not require the addition of IFX to achieve a satisfying clinical and radiological course. So far, no evidence has established the superiority of MTX-IFX over MTX-prednisone or other combinations of traditional disease-modifying anti-rheumatic agents.
16949136 Pathogenesis and management of adult-onset Still's disease. 2006 Dec OBJECTIVE: To review recent literature regarding the pathogenesis and treatment of adult-onset Still's disease (AOSD). METHODS: We searched MEDLINE and PUBMED from 1971 to present using the following terms: adult-onset Still's disease, AOSD, or adult Still's disease. In addition we manually retrieved relevant abstracts from recent American College of Rheumatology and European League Against Rheumatism meetings. RESULTS: The etiology of AOSD, a rare, immune-mediated, multisystem inflammatory disorder characterized by quotidian spiking fevers, evanescent rash, and arthritis, remains unknown. An infectious etiology has been postulated, although a definitive agent has yet to be identified. Cytokines, such as interleukin (IL)-1, IL-6, interferon (IFN)-gamma, and tumor necrosis factor-alpha, are elevated in patients with AOSD. IL-18 and macrophage-colony stimulating factor also seem to play a role. Treatment historically consisted of nonsteroidal antiinflammatory drugs, often in combination with low-dose corticosteroids. Immunosuppressants (mainly methotrexate, but also intramuscular gold, azathioprine, cyclosporine A, leflunomide, and cyclophosphamide) and intravenous gamma-globulin are efficacious and have been used as steroid-sparing drugs. The recently reported use of anticytokine (anti-TNF-alpha, anti-IL-1, and anti-IL-6) agents in refractory cases has opened new horizons in the treatment of AOSD and provided important clues for its pathophysiology. CONCLUSIONS: Advances in immunology have enhanced our understanding of the role of cytokines in AOSD pathogenesis. Early, promising studies of anticytokine agents in AOSD may provide further insight into the pathogenetic mechanisms of this complex disease.
18716298 Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. 2008 Aug 21 BACKGROUND: Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis. METHODS: Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks. RESULTS: Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients. CONCLUSIONS: Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)
18727822 Disseminated cutaneous Herpes Simplex Virus-1 in a woman with rheumatoid arthritis receivi 2008 Aug 26 INTRODUCTION: We present the case of a 49-year-old woman with a seronegative rheumatoid arthritis who developed pustular psoriasis whilst on etanercept and subsequently developed disseminated herpes simplex on infliximab. CASE PRESENTATION: Our patient presented with an inflammatory arthritis which failed to respond to both methotrexate and leflunomide, and sulphasalazine treatment led to side effects. She was started on etanercept but after 8 months of treatment developed scaly pustular lesions on her palms and soles typical of pustular psoriasis. Following the discontinuation of etanercept, our patient required high doses of oral prednisolone to control her inflammatory arthritis. A second biologic agent, infliximab, was introduced in addition to low-dose methotrexate and 15 mg of oral prednisolone. However, after just 3 infusions of infliximab, she was admitted to hospital with a fever, widespread itchy vesicular rash and worsening inflammatory arthritis. Fluid from skin vesicles examined by polymerase chain reaction showed Herpes Simplex Virus type 1. Blood cultures were negative and her chest X-ray was normal. Her infliximab was discontinued and she was started on acyclovir, 800 mg five times daily for 2 weeks. She made a good recovery with improvement in her skin within 48 hours.She continued for 2 months on a prophylactic dose of 400 mg bd. Her rheumatoid arthritis became increasingly active and a decision was made to introduce adalimumab alongside acyclovir. Acyclovir prophylaxis has been continued but the dose tapered so that she is taking only 200 mg of acyclovir on alternate days. There has been no recurrence of Herpes Simplex Virus lesions despite increasing adalimumab to 40 mg weekly 3 months after starting treatment. CONCLUSION: We believe this to be the first reported case of widespread cutaneous Herpes Simplex Virus type 1 infection following treatment with infliximab. We discuss the clinical manifestations of Herpes Simplex Virus infections with particular emphasis on the immunosuppressed patient and the use of prophylactic acyclovir. Pustular psoriasis is now a well recognised but uncommon side effect of antitumour necrosis factor therapy and can lead to cessation of therapy, as in our patient's case.
17583775 Anakinra in patients with treatment-resistant adult-onset Still's disease: four case repor 2007 Dec OBJECTIVE: To determine the efficacy of the interleukin (IL)-1-receptor antagonist (IL-1RA) anakinra in patients with adult-onset Still's disease (AOSD) refractory to standard treatments such as glucocorticosteroids (GC), immunosuppressive drugs, and tumor necrosis factor (TNF)-antagonists; to verify disease remission objectively by serial cytokine measurements; and to review the current literature on anakinra for this indication. METHODS: Four patients with AOSD--2 with acute flares of the chronic form of the disease and 2 with intermittent disease--were treated with prednisolone and methotrexate. One was also treated with several other immunosuppressive drugs including etanercept and infliximab. One patient had life-threatening symptoms (toxic megacolon, pneumonitis, disseminated intravascular coagulation) despite high-dose prednisolone. Treatment with anakinra 100 mg/d subcutaneously was initiated. White blood cells (WBC), C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), liver enzymes, ferritin levels, and serum cytokines were analyzed. The current literature on the efficacy of anakinra for AOSD is reviewed. RESULTS: Patients with chronic AOSD quickly responded to anakinra treatment (1 day to 3 days). GC could be tapered. ESR, CRP, WBC, ferritin, and liver enzymes returned to normal. Serum cytokine measurements revealed moderately elevated IL-1beta levels and highly elevated IL-18 levels in active disease, which normalized with anakinra. TNF-alpha and IL-6 were moderately elevated only in the 2 patients with chronic AOSD. In the literature, 17 similar cases have been reported to date. CONCLUSIONS: Anakinra is effective in treatment-resistant and in life-threatening AOSD. IL-18 serum levels, in addition to CRP, ESR, liver enzymes, ferritin, and WBC, may be helpful in assessing disease activity and response to treatment.
18751844 Combination therapy for rheumatoid arthritis in the era of biologicals. 2006 Feb Early, aggressive disease management is critical for halting disease progression and joint destruction in patients with rheumatoid arthritis. Combination therapy with at least two disease-modifying antirheumatic drugs, such as methotrexate (MTX), sulfasalazine, or hydroxychloroquine, is often more effective than monotherapy in reducing disease activity. Biologic therapies represent more effective and tolerable treatment options that, when combined with MTX, have been shown to dramatically reduce inflammation, inhibit radiographic progression, and induce remission. Although several types of treatment strategies are used in clinical practice, the most aggressive approaches that target early disease have shown the most promise in reversing disease progression and reducing disease-related costs.
18360621 Adalimumab in the treatment of arthritis. 2007 Mar Tumor necrosis factor (TNF) has been implicated in a number of arthritic disease states, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Adalimumab is the first fully human, high-affinity, recombinant immunoglobulin G(1) (IgG(1)) anti-TNF monoclonal antibody. Adalimumab in combination with methotrexate or standard antirheumatic therapies, or as monotherapy, is effective in the treatment of adults with active rheumatoid arthritis who have had an inadequate response to disease-modifying antirheumatic drugs. Adalimumab is also effective in the treatment of patients with moderately to severely active psoriatic arthritis, improving both joint and skin manifestations of the disease as well as disability due to joint damage. In the Adalimumab Trial Evaluating Long-term Efficacy and Safety in Ankylosing Spondylitis (ATLAS), adalimumab significantly reduced the signs and symptoms of active ankylosing spondylitis and established a sustained clinical response in patients who had an inadequate response or intolerance to nonsteroidal antiinflammatory drug therapy. Overall, across these indications, adalimumab demonstrated a rapid onset of action, sustained efficacy with long-term treatment, and was well-tolerated, with few patients discontinuing treatment because of adverse events. The safety profile was similar to other TNF antagonists. Inhibition of TNF activity by adalimumab also significantly improved physical functioning and quality of life measures.
17611347 Celiac disease: association with adult-onset Still's disease: apropos of a clinical case. 2007 Jul Adult-onset Still's disease (AOSD) is a rheumatic disorder of unknown etiology characterized by a triad of fever, polyarthritis and evanescent rash. We present a case report of a 28-year-old female who presented with complaints of fever, joint pains, rash, weakness for the past 4 years and diarrhea for the past 2 years. On investigation the patient was diagnosed to be a case of AOSD. Duodenal biopsy report was suggestive of celiac disease with a positive IgA tissue transglutaminase and anti-endomysial antibody. The patient was started on weekly methotrexate and gluten-free diet and her symptoms gradually improved. The patient remains in our follow-up and is doing well.