Dose reduction of TNF blockers in rheumatoid arthritis: clinical and pharmacological aspects (original) (raw)
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Infliximab treatment of rheumatoid arthritis
Rheumatic Disease Clinics of North America, 2004
The characterization of tumor necrosis factor a (TNF-a) and other cytokines as molecular entities in the mid-1980s provided experimental tools for evaluating their role in the pathogenesis of rheumatoid arthritis (RA) [1]. The accumulating evidence that TNF-a played a unique role in regulating the cytokine network and other inflammatory pathways and therefore was an attractive therapeutic target met with considerable skepticism at the time [2,3]. The first trial of TNF-blockade-performed by our group in London in 1992-1993 with favorable results-dispelled these concerns. It encouraged and set the scene for the development of the three anti-TNF biodrugs that have established a place in the contemporary options available for the treatment of rheumatoid arthritis and other immune-inflammatory diseases. Proof of principle trials The initial experience of the treatment of RA with infliximab (Remicade, originally known as cA2) was planned in an open-label phase I/II trial conducted in 1992-1993 [4]. A dose of 20 mg/kg was derived by extrapolation of the dose of a monoclonal anti-TNF antibody used in a study in murine collagen-induced arthritis in which anti-inflammatory effects and protection of cartilage and bones
Infliximab in the treatment of rheumatoid arthritis
Aging Health, 2006
Rheumatoid arthritis is a chronic inflammatory systemic autoimmune disorder characterized by symmetric inflammation of synovial joints, leading to progressive erosion of cartilage and bone. Tumor necrosis factor-α antagonists have set a new therapeutic standard for rheumatoid arthritis. Tumor necrosis factor-α blocking agents, including infliximab, etanercept and adalimumab, have demonstrated substantial improvement in signs and symptoms, disability and quality of life, while significantly inhibiting joint damage in early and long-standing rheumatoid arthritis. The focus of this article will be the role of infliximab in the treatment of rheumatoid arthritis.
Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis
New England Journal of Medicine, 2000
Background Neutralization of tumor necrosis factor a (TNFa) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. Methods We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNFa , in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. Results The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6; P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response. Conclusions In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
Rheumatoid Arthritis: Refractory to Infliximab, a Tumor Necrosis Factor Inhibitor
Journal of Clinical Medicine Research, 2011
Rheumatoid arthritis is one of the commonest autoimmune diseases. It is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis. If left untreated, it leads to joint destruction and thus deformity and disability. In the recent years, advances in molecular biology have led to a variety of new treatment approaches to rheumatoid arthritis and other systemic inflammatory diseases associated with autoimmunity. Anti tumor necrosis factor (TNF) agents are emerging in the frontline management of rheumatoid arthritis (RA) in the current era of biological treatment. We presented a 46-year-old Chinese female with a history of seropositive RA for the past 22 years refractory and intolerant to multiple medications including sulphasalazine (SSZ), leflunomide, hydroxychloroquine (HCQ) and methotrexate (MTX), thus infliximab, a tumor necrosis factor (TNF) inhibitor was initiated. However, despite receiving 6 cycles of infliximab therapy, she still complained of persistent disabled multiple joint pain and swelling. This report will discuss about rheumatoid arthritis, which is refractory to infliximab (a TNF inhibitor) and its alternative.
International Journal of Rheumatic Diseases, 2012
Background: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting synovial joints and many other organs. Most patients seen in clinical settings have a progressive chronic disease, with radiographic damage, frequent work disability, incremental functional declines and increased mortality rates. The introduction of the biological drugs in treatment of RA has played an important role in prevention of destructive effects of the disease but may have serious adverse effects due to their powerful inhibition of the immune system. Objectives: To study the adverse effects (ADEs) of three different tumor necrosis factor a inhibitor (TNFi) drugs (infliximab, adalimumab and etanercept) in RA patients for 5 years in the southwest area of Saudi Arabia. Methods: Two groups of RA patients were included in this study: The first group included 112 patients, representing the biologics group. These patients received biological therapy plus disease modifying anti-rheumatic drugs (DMARDs): 56 patients received infliximab (IFX), 36 patients received adalimumab (ADL) and 20 patients received etanercept (ETN). The second group also included 112 patients, representing the control group: RA patients treated only with the traditional DMARDs. ADEs were classified into mild and severe. Results: The mild ADEs which had been recorded during 5 years of follow-up in patients receiving TNFi, were onycholysis (1.8%), positive tuberculin test (1.8%) and small vessel vasculitis (1.8%). Statistically, there were insignificant differences in the mild ADEs except for upper respiratory tract infection that was significantly higher in the control group. Severe ADEs included pneumonia (1.8%) and solid tumor (1.8%) and there were no significant differences between the biologics and control groups. Also there were no significant statistical differences for the ADEs, mild or severe, between the three biologics, infliximab, adalimumab and etanercept. Occurrence of ADEs did not correlate to methotrexate dose, steroid dose or rheumatoid factor positivity. Conclusions: Our results indicate that the use of TNFi therapy appeared to be as safe as traditional DMARDs in treatment of rheumatoid arthritis patients and long-term follow-up with careful examination is essential to pick up any abnormal ADEs.
Annals of the Rheumatic Diseases, 2004
Background: Randomised controlled trials have shown that treatment with anti-tumour necrosis factor (anti-TNF) agents is effective in refractory rheumatoid arthritis (RA). Objective: To determine the effectiveness of anti-TNF in a general unselected group of patients with refractory RA. Methods: 68 patients with active RA despite treatment with disease modifying antirheumatic drugs were studied during 12 infliximab infusions. Infliximab (3 mg/kg/infusion) was given every 8 or 6 weeks. Clinical efficacy was assessed by the Disease Activity Score (DAS) index (44 joints). Dose adjustments were based on residual disease activity (DAS score .2.4). The primary end points were the percentage of patients achieving good or moderate response by the EULAR response criteria and the proportion of patients requiring dose adjustment. Results: 20 (29%) patients discontinued treatment owing to side effects, early inefficacy, or other considerations. Among the patients who continued treatment, 27 (56%) and 32 (67%) were responders on the 6th and 12th infliximab infusion, respectively. In the same patients, disease activity gradually improved without modifications in the initial dosing in 10 (21%), whereas in 38 (79%) the dose of infliximab and/or methotrexate was increased. Intensification of treatment led to a significant decrease in the mean DAS score in this group (from 5.27 just before dose modification to 4.54 before the 12th infusion, p,0.002). The EULAR response category improved in only 10/38 (26%), however. Conclusions: In this initial observational study of patients with RA treated with recommended doses of infliximab, adjustments in treatment were common but not always sufficient to maintain adequate disease control. Longitudinal controlled trials are needed to define the optimal dose escalation in patients with suboptimal response.
Rheumatoid Arthritis: Brief Overview of Diagnosis and Treatment along with Disease Management
Journal of Pharmaceutical Research International, 2021
Background: Rheumatoid Arthritis (RA) is a multisystem illness specifically marked through chronic distension and joint destruction. Time of life, gender, heredity, and ecological familiarity are risk factors (cigarette smoking, air contaminants, and industrial). If left untreated, Felty disorder can lead to permanent joint damage needing arthroplasty, rheumatic vasculitis, rheumatic vasculitis, and rheumatic vasculitis necessitating splenectomy. Because RA is noncurable, the focus of action is on reducing discomfort and preventing additional damage via rest. In this article, I provide a brief overview of various previous and current reporting mechanisms for RA-related issues. Description: RA is a debilitating, long-term illness that can cause joint deterioration and incapacitating symptoms. Initial analysis, in addition to participation, is crucial in preventing grave damage and the forfeiture of dynamic bodily roles. Autoantibodies including rheumatoid factor (RF) and anti cyclic ...
2020
ABSTRACT. Objective. To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA). Methods. We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment.
Treatment of rheumatoid arthritis patients – a challenge
Romanian Journal of Rheumatology, 2020
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease with unclear etiology that involves the peripheral joints symmetrically, causing synovial hypertrophy, inflammation and, consequently, erosions of the bone and cartilage. We hereby present the case of a 51-year-old female patient diagnosed with RA in 2009 for which she received treatment with Methotrexate and TNF alpha treatment (Infliximab). Prior to the first dose of Infliximab Quantiferon-TB Gold was performed with a negative result. In 2016 the patient presented with ascites and pleural effusion with a positive repeated test for Quantiferon-TB Gold, the treatment with Infliximab and Methotrexate was stopped and she was started on anti TB standard treatment regimen for 9 months with the remission of the polyserositis. After the completion of the anti TB treatment we reinitiated Methotrexate therapy given a high disease activity (DAS28-CRP of 6.59) which improved the patients complaints; however, 3 months later, given an increase in the patients inflammatory markers we performed a computed tomography (CT) scan that revealed peritoneal thickening, and several omental nodules, the histological examination confirming the diagnosis of peritoneal TB. The patient was reinitiated on the anti-TB treatment.