Gene therapy for rheumatoid arthritis

Rheumatoid arthritis (RA) is a painful chronic disorder. Conventional therapies are palliative, not curative. Advances in the understanding of the pathophysiology of RA have led to the development of new therapeutic strategies, including gene therapy. Multiple studies in several different animal models provide proof supporting the use of gene therapy in arthritis. A phase I clinical trial has already been performed successfully on nine women with end-stage RA in the United States, and two other trials are in progress. Limited duration of gene expression impedes the development of a clinically useful genetic treatment for arthritis.     

Chimeric cd4 monoclonal antibody cm-t412 as a therapeutic approach to rheumatoid arthritis

Objective. To investigate the effects of chimeric CD4 monoclonal antibody cM-T412 treatment in patients with rheumatoid arthritis (RA). Methods. Thirty-two RA patients received daily doses of 10, 50, or 100 mg of cM-T412 intravenously for 7 days. Results. There was a sustained decrease in the number of CD4+ T lymphocytes in all patients. Those who received 50 mg and 100 mg of the antibody experienced significant reductions in disease activity. Conclusion. Treatment with cM-T412 appears to have a dose-dependent beneficial effect in RA patients. The clinical effects of cM-T412 are independent of the depressed numbers of circulating CD4+ T cells.     

Safety and efficacy of alternate-day corticosteroid treatment as adjunctive therapy for rheumatoid arthritis: a comparative study

Corticosteroids (CSs), used to treat rheumatoid arthritis (RA), confer a risk of adverse events (AEs). This study investigated the safety and efficacy of alternate-day (QOD) CS therapy for RA. All patients (>?18 years) who started oral CS therapy for RA, between 2005 and 2014, at our hospital were retrospectively analysed. The patients were divided into the daily (QD) and QOD CS therapy groups to investigate the rates of CS-related major AEs (infection, diabetes, hypertension, cardiovascular events and fragility fractures) within the first year of treatment. The number of patients free from CS treatment at 1 year and the mean decreases in C-reactive protein (CRP) levels at 1 month were also investigated. In total, 138 patients were analysed (QD group, 68; QOD group, 70). The maximum daily CS dose was not significantly different between the two groups, but the annual cumulative dose was significantly lower in the QOD group (P?<?0.01). The infection rate was significantly lower in the QOD group (24.3%) than in the QD group (50.0%; P?<?0.01), whereas the other AE rates were similar between the groups. The CS-free rate at 1 year was significantly higher in the QOD group (58.6%) than in the QD group (26.5%; P?<?0.01). The mean CRP decreases over 1 month of CS therapy were not significantly different between the groups. QOD CS treatment leads to a lower infection rate and less CS dependence than does daily treatment; both RA treatments are equally effective.     

Co-stimulatory blockade as therapy for rheumatoid arthritis

There is substantial evidence that rheumatoid arthritis is an autoimmune disease in which T cells are aberrantly activated. Existing therapies, including anti-tumor necrosis factor therapies, are successful for many patients, but the goal of lasting remission still frequently proves elusive. One novel therapeutic strategy is the blockade of T-cell co-stim-ulation to modulate T-cell activation. The first co-stimula-tion blocker to reach clinical trials is abatacept (CTLA4Ig). Initial abatacept trials have shown promise and further phase III trials are underway.     

Biological modifier therapy for the treatment of rheumatoid arthritis

The recent elucidation of pathogenic processes involving tumor necrosis factor alpha and interleukin-1beta in the pathogenesis and persistence of rheumatoid arthritis led to the development of biological modifier agents that have had significant impact on disease severity and progression. These agents--etanercept, infliximab, and anakinra--produce a dramatic reduction in RA disease activity with relatively low toxicity compared with currently available disease-modifying antirheumatic drugs. The main prohibition to their broader utilization is cost. The success of these agents underscores the investigative approaches to the pathogenesis of RA and the appropriate design of pharmaceutical agents to target specific proinflammatory molecules.     

High-dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis

Objective. To investigate the efficacy of high-dose intravenous immunoglobulin (IVIg) in the treatment of refractory rheumatoid arthritis (RA). Methods. Ten patients with active, severe RA that was unresponsive to first- and second-line agents were administered IVIg monthly, for 6 months. Results. Following IVIg treatment, there was significant improvement in both subjective and objective parameters of disease activity in all 9 patients who completed the protocol. This improvement was noted to occur as early as after the second infusion of IVIg. After discontinuation of the treatment, all patients had a relapse of the disease within a few weeks. Conclusion. Since the reduction in clinical activity paralleled a decrease in the CD4+CDw29+: CD4+CD45RA+ cell ratio, some of the therapeutic benefits associated with IVIg may be due to a direct influence on the CD4+CD45RA+ subset. Although the possibility of carrying out further controlled studies on a larger scale is limited by the high cost of the treatment, IVIg appears to be an effective therapy for refractory RA.     

Remodeling the therapeutic pyramid: evolving therapeutic strategies for rheumatoid arthritis

The approach to treatment of rheumatoid arthritis (RA) is undergoing dramatic change, With a prevalence of 1% of the general population. RA is the most common cause of disability that is potentially reversible if correct management of the disease is begun in the early phases. While the traditional therapeutic pyramid model has been in place for the past 25 years, evolving therapeutic strategies suggest that it is appropriate primarily for patients with benign synovitis, and an inverted pyramid is necessary to treat aggressive synovitis, control inflammation early and to prevent rapid joint destruction, disability and early death. Important principals underlying the remodeling of the therapeutic pyramid and evolving therapeutic strategies include: identifying patients with benign and aggressive synovitis: early control of inflammation to stabilize functional status at near normality; need for combination therapy in aggressive synovitis until a major breakthrough or ‘magic’ bullet becomes available; awareness that drugs that control inflammation in a more fundamental manner, such as disease-modifying anti-rheumatic drugs, are more effective in pain control and disability than non-steroidal anti-inflammatory drugs; and, most importantly, education of patients, primary and managing care physicians, health maintenance organizations, insurance companies, and government officials that two-thirds of the cost of RA lies in the complications of the disease and that providing resources for early aggressive therapy is a good investment for all. Successful treatment of rheumatoid arthritis is best accomplished by a coordinated team of a consultant rheumatologist and a managing primary care physician. Much like an early consultation with an oncologist when cancer is suspected, an early consultation with a rheumatologist can help separate benign and aggressive synovitis. If the latter, the rheumatologist can help identify important co-morbid conditions and recommend appropriate therapy. Follow-up programs can then be outlined to maintain control of inflammation at all times, utilize appropriate pharmacologic and non-pharmacologic physical and occupational therapy modalities for mechanical pain, and highlight potential toxicities to be monitored. This program, initiated early, will help prevent administration of toxic drugs to patients with benign synovitis. And, just as important for patients with aggressive synovitis, this strategy is designed to reduce the high incidence of morbidity and mortality and the costly episodes of hospitalizations and salvage surgery that can be so devastating to patients and their families.     

B-cell inhibitors as therapy for rheumatoid arthritis: An update

A revolution in the treatment of rheumatoid arthritis has occurred in recent years. This holds particularly true for B-cell-directed therapies for rheumatoid arthritis. The approval of rituximab for the treatment of rheumatoid arthritis has not only expanded the armamentarium of therapies for rheumatologists, but it has also led the way to better understanding of the biologic sequelae of these treatments as well as the potential to better understand the etiology of autoimmune diseases. This review updates the latest B-cell therapies in rheumatoid arthritis.     

Identification of hub genes and therapeutic drugs in rheumatoid arthritis patients

Clinical Rheumatology - Rheumatoid arthritis (RA) is considered a chronic autoimmune inflammatory disease that causes great morbidity and shortens life expectancy; however, the precise pathogenesis...     

性激素替代疗法对类风湿关节炎疗效的系统评价

目的 探讨性激素替代疗法(HRT)对类风湿关节炎(RA)的疗效.方法 检索国内外公开发表的关于HRT治疗RA的随机对照试验文献,筛选合格文献进行研究,运用异质性检验、Meta分析等方法统计相关数据.结果 共有11项研究符合纳入标准.HRT与安慰剂相比能够降低RA患者的红细胞沉降率(ESR)水平,标准均数差(SMD)为-0.22(-0.40,-0.04),P=0.016;升高患者的骨密度水平,加权均数差(WMD)为2.83(0.41,5.26),P=0.022;降低患者的临床评价指标,SMD为-0.19(-0.38,0.00),P=0.048;降低患者的C反应蛋白(CRP)水平,SMD为-0.08(-0.37,0.21),但差异不具有统计学意义(P=0.591).结论 Meta分析结果显示,HRT能够降低RA患者的ESR水平及临床评价指标,并提高患者的骨密度水平,HRT能够减轻RA患者的病情活动并且抑制骨质疏松,可作为RA治疗的新方法或辅助治疗手段.     

Methotrexate therapy in the treatment of rheumatoid arthritis

MTX has been demonstrated to be one of the most effective agents in current use for the treatment of patients with active RA who have failed other approaches. Therapy must be individualized to achieve an optimal efficacy/toxicity profile. The drug is a potent steroid-sparing agent which is a factor of marked significance in this patient group. Although cellular activity is well described, many unanswered questions about its absorption, target cell population, and mechanism of action remain. More information is needed about the true incidence of long-term toxicities to be able to better address the all important issue of when to use MTX in the treatment of RA. Research efforts, including studies of immunologic parameters over time, are needed to achieve a better understanding of the drug's mechanism of action. Lastly, the reasons for the plateau in clinical response to MTX should be explored to devise strategies to enhance and sustain the effects of this already potent drug.