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ID PMID Title PublicationDate abstract
20421913 Critical appraisal of tocilizumab in the treatment of moderate to severe rheumatoid arthri 2010 Apr 15 Recent advances in our understanding of the role of interleukin (IL)-6 in autoimmunity and in particular rheumatoid arthritis (RA) have brought about important changes in the way we think about autoimmune diseases. Encouraging data from several phase III clinical trials of tocilizumab, a humanized monoclonal antibody against IL-6R, have led to its approval in Europe for the treatment of moderate to severe RA. Data on clinical efficacy, patient-reported outcomes, safety, and cost-effectiveness with the use of tocilizumab in patients with RA will be summarized in this review, with particular emphasis on phase III clinical trials. Furthermore, adverse events associated with the use of tocilizumab will be reviewed. Future clinical trials will evaluate the role of tocilizumab in other autoimmune diseases. The goal of this review is to describe the current understanding of the role of IL-6 in mediating the inflammatory response in RA, as well as the role of tocilizumab in the treatment of RA and the evolving role of this agent in other autoimmune diseases.
19851470 Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of cur 2009 Enhanced understanding of the rheumatoid arthritis (RA) pathophysiology and the role of cytokines has enabled the development of innovative biological agents in the last 10 years that target specific parts of the immune response. Failure to achieve adequate response with traditional disease modifying anti-rheumatic drugs (DMARDs) and increasing evidence of ongoing radiographic deterioration of the affected joints despite seemingly clinical response were essential stimuli for the development of biologics. The current and upcoming biological agents are primarily aimed at neutralizing circulating and cell-bound pro-inflammatory cytokines, interfering in the interaction of antigen-presenting and T-lymphocytes, eliminating circulating B-lymphocytes or by interfering with the intracellular signaling mechanisms of immuno-competent cells that lead to inflammation. These agents have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. However, use of these agents has also been associated with significant, although rare, adverse events and considerable cost. Therefore, these agents should be used with caution by experienced clinicians. The present work aims to provide a global and updated review of the current and in-development biological DMARDs for the treatment of RA.
22870439 Using hand bone mass measurements to assess progression of rheumatoid arthritis. 2010 Apr In rheumatoid arthritis (RA) bone involvement presents as joint erosions in addition to generalized and periarticular osteoporosis. Joint erosions on radiographs of the hands and feet are considered to be the gold standard to evaluate progression of bone and joint damage in RA, even though erosions on radiographs are not used as a marker of early bone involvement. Periarticular bone loss seen on radiographs may be the first sign of bone involvement in RA. Over the last decade there has been an increased awareness of the importance of early aggressive treatment in RA, leading to a need for methods which can identify bone involvement in the early stages of RA. As inflammatory bone loss, especially at the hand, has been shown to occur early in RA, quantitative measures of hand bone loss have been proposed as an outcome measure for the detection of bone involvement. In this review article we present data supporting the hypothesis that both erosions and osteoporosis in RA occur as a result of the same pathophysiological mechanisms activating the osteoclast. Furthermore the role of hand bone loss as an early marker of inflammatory bone involvement, a predictor of subsequent radiographic joint damage and a response variable to anti-inflammatory treatment is discussed.
22870440 The efficacy and safety of abatacept in rheumatoid arthritis. 2010 Apr Despite important progress in the treatment of rheumatoid arthritis in the last decade, even in the era of tumour necrosis factor (TNF) blockade there is a need for additional therapeutic options in many patients. In recent years three therapies with a distinct mode of action became available: rituximab, an anti-B cell therapy, tocilizumab, an anti IL-6 therapy, and abatacept, a costimulation blocker. Primary efficacy results of all three therapies are comparable at 6 months, nevertheless they have distinct efficacy and safety profiles. In the current review we focus on specific aspects of efficacy and safety of abatacept: increasing clinical and X-ray improvements over time, important and stable responses over several years, timing of response, improvements in patient-centered outcomes, and also long-term safety and easy administration with low rates of perfusion reactions. Currently, head to head comparisons between biologics are still lacking and registry data of drugs with a mode of action different to TNF blockade are still rare. In the meantime detailed analysis of all trials with a drug such as abatacept provides important information for the practicing rheumatologist.
20054439 Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of th 2009 OBJECTIVE: To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis. METHODS: We searched MEDLINE((R)), Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs) comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data. RESULTS: We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA). The pooled relative risk (RR) of an ACR50 (American College of Rheumatology) response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67). Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17) favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7) of patients experienced an injection site reaction. CONCLUSIONS: Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into account when considering biologic therapy for patients with RA.
19918491 A rare complication of a metacarpophalangeal joint replacement in a rheumatoid hand: a cas 2009 Sep 10 Metacarpophalangeal joint replacement is one of the most common surgery performed for rheumatoid hand deformities. The systemic and progressive nature of rheumatoid arthritis and other inflammatory arthritis make isolated assessment and treatment of metacarpophalangeal joint joints challenging.Extensive joint involvement and systemic nature of the illness has an impact in the prognosis of the illness. The long term outcome of the surgical procedure depends on how best the illness is controlled. Technical aspects of the surgery in patients with rheumatoid arthritis can be widely variable and can make implant arthroplasty challenging. We present a case report of an unusual presentation of a rare complication following metacarpophalangeal joint replacement performed 17 years ago.
20110522 Associated autoimmune diseases in systemic sclerosis define a subset of patients with mild 2010 Mar OBJECTIVE: To assess the prevalence and potential associations with the systemic sclerosis (SSc) phenotype of additional autoimmune diseases (AID). METHODS: A multicenter study was performed in France and Italy to recruit consecutive European Caucasian patients with SSc systematically assessed for the coexistence of predefined AID known to occur with connective tissue diseases. RESULTS: We recruited 585 French and 547 Italian patients with SSc. Specific AID were found in 114/585 (19%) French and 179/547 (33%) Italians with SSc (p < 0.0001). Sjögren's syndrome and thyroiditis were the predominant AID in both cohorts (12% for Sjögren's syndrome and 6% for thyroiditis in the combined populations). The frequency of myositis, primary biliary cirrhosis, rheumatoid arthritis, and systemic lupus erythematosus was low (< 4%) and similar in both cohorts. The coexistence of at least 1 of the AID in the whole cohort was associated in multivariate analysis with the limited cutaneous subtype, the presence of antinuclear antibodies, and a lower prevalence of digital ulcers. CONCLUSION: Our study shows that 21% of this large series of European Caucasian patients with SSc have developed at least 1 AID. This latter condition identified a subset of patients with milder disease. Thus, associations of AID and autoimmune background in SSc have to be considered for further therapeutic and biological investigations in SSc.
22915918 Prefilled certolizumab pegol (Cimzia(®)) syringes for self-use in the treatment of rheuma 2010 A new anti-tumor necrosis factor alpha (TNF-α) inhibitor with a novel mechanism of action has entered phase 3 trials in rheumatoid arthritis (RA). Certolizumab pegol (Cimzia(®)) is a humanized Fab' antibody fragment against TNF-α with a polyethylene glycol tail that prevents complement-dependent and antibody-dependent cell-mediated cytotoxicity or apoptosis. Four randomized clinical trials have been published so far. Reported results are similar to those published in previous studies with other TNF-α inhibitors, with ACR20, ACR50, and ACR70 responses of around 60%, 40%, and 20%, respectively, when combined with methotrexate and slightly lower when used as monotherapy. Safety was shown to be similar to that seen with TNF-α blockers and some cases of tuberculosis were seen in the trials, stressing the importance of a complete screening in these patients. Although we still need effectiveness and safety data in larger numbers of patients and longer follow-up, this new TNF inhibitor is a welcome addition to our current armamentarium for the treatment of RA.
21072312 The use of anti-TNFα medications for rheumatologic disease in pregnancy. 2010 Aug 9 Anti-TNFα medications have led to vast improvements in the treatment of inflammatory conditions, including rheumatoid arthritis and Crohn's disease. As these diseases often afflict women in their reproductive years, the safety of these drugs during pregnancy is an important issue. Prospectively collected data thus far appear to be reassuring; however an analysis of the FDA-reported anomalies has raised some questions. It appears that significant levels of these drugs cross the placenta as the pregnancy nears term, but little is passed through breast milk. Prior to using these medications during pregnancy, the risks and benefits of these drugs, other treatment options, and the ongoing inflammatory condition all must be carefully weighed by both doctor and patient.
21701636 TNF-α inhibitors: are they carcinogenic? 2010 Biologic therapy has increasingly been used in the treatment of chronic diseases. Tumor necrosis factor (TNF) is a cytokine implicated in the pathogenesis of rheumatoid arthritis and inflammatory bowel disease. Anti-TNF therapy is being used in the treatment of these conditions. Since the introduction of anti-TNF agents, there have been many case reports of development of malignancy after the initiation of anti-TNF therapy. With increasing case reports, there is growing concern that anti-TNF therapy, albeit useful in the treatment of these chronic conditions, might be associated with the development of malignancy in patients. In this review we examine the different anti-TNF agents and different studies to evaluate any possible association between use of any anti-TNF agent and development of malignancy.
29788606 Recent advances in personalizing rheumatoid arthritis therapy and management. 2009 Mar Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterized by synovial inflammation in diarthrodial joints. There are significant interindividual variations in the degree of inflammation, disease course and the rate of joint progression in patients with RA. A number of clinical, serological, environmental and genetic severity factors have been identified in patients with RA and can be used to help guide treatment. Therapeutic options for RA have significantly expanded in the last decade and now include both synthetic disease-modifying antirheumatic drugs as well as biologic disease-modifying antirheumatic drugs. Owing to the variety of new drugs, their cost and incomplete information on side effects, markers of treatment response are needed. The study of treatment-specific genetic and protein biomarkers of response and toxicity in RA has produced exciting, yet inconsistent, results. Large scale genetic and proteome studies, which can now be performed at a relatively low cost, will likely broaden the scope and significance of biomarker studies in RA. Integration of these results into clinical practice will vastly improve our ability to provide safe and effective therapy to individuals with RA.
20617213 A 21-year-old man with systemic-onset juvenile rheumatoid arthritis, cough and progressive 2010 May Primary or nonobstructive, endogenous lipoid pneumonia is a rare clinical entity usually associated with an underlying systemic disease. The present report describes a case involving a 21-year-old man with systemic-onset juvenile rheumatoid arthritis who developed primary endogenous lipoid pneumonia. Multiple treatment regimens were attempted; however, definitive management was only achieved through double-lung transplantation.
27789998 Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthr 2010 Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been in routine clinical use for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis for a decade. In RA, clinical trials of up to two years' duration showed that leflunomide monotherapy was equivalent to methotrexate in clinical and radiographic disease outcomes (tender and swollen joint counts, physician and patient global assessments, American College of Rheumatology and Disease Activity Score responses, slowing or halting of radiographic progression). In a number of studies, quality of life measurements indicated that leflunomide is superior to methotrexate. Leflunomide has been studied in combination with methotrexate and shows efficacy in patients only partly responsive to this agent. Recent trials have shown that leflunomide can be used safely with biologic DMARDs, including antitumor necrosis factor agents and rituximab as part of the treatment algorithm in place of methotrexate as a cotherapy. Leflunomide has demonstrated efficacy as a monotherapy in psoriatic arthritis, and it also has a beneficial effect in psoriasis. Postmarketing studies have shown that retention on treatment with leflunomide is equal to methotrexate and superior to other DMARDs. In general, its side effect profile is acceptable compared with other DMARDS, with nausea, diarrhea, and hair fall occurring commonly, but only rarely leading to discontinuation. Liver toxicity is the most significant problem in clinical use although it is uncommon. Peripheral neuropathy, hypertension, pneumonitis, and cytopenia occur more rarely. Leflunomide is contraindicated in pregnancy and should be used with caution in women during child-bearing years. In this review, the place of leflunomide in therapy is discussed and practical advice informed by evidence is given regarding dosing regimens, safety monitoring, and managing side effects. Leflunomide remains one of the most useful of the nonbiologic DMARDs.
19707407 Infliximab in the treatment of rheumatoid arthritis. 2009 Infliximab was the first monoclonal antibody to human necrosis factor alpha (TNFalpha) developed for treating rheumatoid arthritis (RA). This chimeric antibody binds with high affinity to both soluble and trans-membrane TNF and is able to reduce synovial inflammation, bone resorption and cartilage degradation. The efficacy of infliximab has been observed in active RA despite treatment with multiple disease modifying anti-rheumatic drugs (DMARDs), and in early disease with no prior treatment by methotrexate (MTX). Infliximab has been shown to reduce joint inflammation and to slow radiographic progression, in both clinical and non-clinical responders. Recent data suggest that using infliximab early in RA treatment increases the percentage of clinical remission and allows infliximab discontinuation. The recommended dosage of 3 mg/kg could be increased up to 10 mg/kg with partial efficacy of the dose escalation. Antibodies to infliximab have been observed in 7% to 61% of patients and are associated with a low trough level of infliximab and secondary response failure. Their occurrence could be prevented by co-medication with MTX. The combination of DMARDs other than MTX with infliximab was found to be safe and efficacious. Infections, principally tuberculosis, are increased in treated patients, and the risk is greater at higher dose. Even if the treatment is generally safe and well tolerated, patients treated with infliximab should be closely monitored.
21187863 Change of the aortic elasticity in rheumatoid arthritis: Relationship to associated cardio 2010 Jul INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease, which is associated with an excess of cardiovascular events. A decrease in the compliance of the arterial system, termed arterial stiffness, results in increased cardiac workload. Primary prevention of cardiovascular disease (CVD) is a priority for modern medicine. Therefore, further studies are required to explore the mechanisms through which CVD increases in RA. PATIENTS AND METHODS: This case-control study was performed to detect possible change of aortic elasticity in patients with RA, and to estimate the impact of different cardiovascular and atherogenic risk factors on the severity of arterial stiffness. Sixty-three consecutive adults with RA were enrolled for the study (case group). Forty-one healthy adults matched for age and gender were considered as a control group. All were subjected to assessment of aortic stiffness index and various cardiovascular risk factors. Patients with rheumatoid disease (case group) were divided by their aortic stiffness index status to two groups (A and B, with and without aortic stiffness, respectively). RESULTS: Aortic stiffness was present in 31.7% of the RA patients. Age of the patients, duration of RA, smoking index, waist circumference, triglycerides levels, and CRP were significantly higher in patients with aortic stiffness. CONCLUSION: RA is associated with decreased elasticity of the aorta in both genders, and such changes seem to be higher in the presence of visceral obesity, smoking, high triglycerides, and extraarticular disease severity.
21686829 Diffuse mesangial IgA glomerulonephritis in a patient with rheumatoid arthritis: a possibl 2009 Rheumatoid arthritis (RA) is an inflammatory joint disease, in which, unlike systemic lupus erythematosus (SLE), renal involvement is uncommon. The major causes of renal disease in RA are usually linked to amyloid or secondary effects of drugs. Nevertheless the relation between IgA, IgA-rheumatoid factor (RF) and renal disease in patients with RA is not clear, but the affinity of IgA for mesangium, skin and synovium might explain clinical presentation of RA with mesangial IgA glomerulonephritis. The case of a 42-year-old Caucasian man with RA and diffuse mesangial IgA glomerulonephritis proven by renal biopsy is presented. The patient was treated with boluses of methylprednisolone 1000 mg and cyclophosphamide 1000 mg monthly for 13 months. Between boluses there was a supported therapy with methylprednisolone 8 mg/day. After a year of treatment full clinical and laboratory remission of RA and IgA glomerulonephritis was achieved. Pathogenic therapy will be stopped and the patient followed-up.
21977172 Extra-articular Manifestations in Rheumatoid Arthritis. 2010 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function.Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjögren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjögren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common - in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA.This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system.
19280925 [Sjögren's syndrome]. 2009 Mar Sjögren's syndrome (SS) is chronic autoimmune disease characterized by destructive lymphocyte infiltration of salivary and lacrimal glands, which results in dry eyes and dry mouth. Despite extensive study of the underlying cause of SS, the pathogenesis remains obscure. The Sjögren's International Collaborative Clinical Alliance (SICCA) by five Research Groups located in Argentina, China, Denmark, the United States and Japan, is the first registry and clinical data-specimen repository to establish the International Standard Criteria for diagnosing SS. Patients with SS have a relative increased risk for development of B cell lymphoma compared with other autoimmune rheumatic diseases. We discuss the possible mechanisms for lymphoma development. The topics concerning SS is IgG4-related lymphoproliferative diseases, such as Mikulicz's disease and autoimmune pancreatitis. Based on the analysis of patients registered from all over Japan, we propose a new clinical entity IgG4-positive multi-organ lymphoproliferative syndrome (IgG4+ MOLPS).
21686603 New onset psoriasis in a patient receiving abatacept for rheumatoid arthritis. 2009 Administration of abatacept is a new treatment modality for rheumatoid arthritis (RA). We describe a patient in whom psoriasiform skin lesions developed 4 months after the initiation of abatacept therapy for longstanding, rheumatoid factor positive RA. Histological findings were consistent with psoriasis. The skin lesions subsided after discontinuation of abatacept and reappeared after re-exposure to the drug, suggesting a causal connection between abatacept and the development of psoriasis.
20694072 Golimumab: A novel human anti-TNF-alpha monoclonal antibody for the treatment of rheumatoi 2010 Jun 15 INTRODUCTION: The introduction of tumor necrosis factor-alpha (TNF-alpha) inhibitors represented a significant advance in the management of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Although three TNF-alpha inhibitors have been approved for the treatment of RA by the US Food and Drug Administration (FDA) and the European Medicinal Products Evaluation Agency (EMEA), not all patients achieve a satisfactory clinical improvement with these therapeutic agents. The mode of administration of these medications is inconvenient for some patients. AIMS: Golimumab is a novel anti-TNF-alpha monoclonal antibody that is in clinical development for the treatment of RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS), either as a first-line biologic therapy or an alternative after other TNF-alpha inhibitors have been discontinued. This review summarizes the development of, and clinical evidence achieved with, golimumab. EVIDENCE REVIEW: Golimumab has demonstrated significant efficacy in randomized, double-blind, placebo-controlled trials when administered subcutaneously once every four weeks. It has been generally well tolerated in clinical trials and demonstrates a safety profile comparable with currently available TNF-alpha inhibitors. OUTCOMES SUMMARY: Golimumab has been confirmed to be an effective treatment for patients with RA, PsA, and AS in phase III clinical trials as evaluated by traditional measures of disease activity, such as signs and symptoms, as well as measures of physical function, patient reported outcomes, and health economic measures. The efficacy and safety profile of golimumab in RA, PsA, and AS appears to be similar to other anti-TNF agents. However, golimumab has the potential advantage of once monthly subcutaneous administration and the possibility of both subcutaneous and intravenous administration.