Hungarian Immunology

[Rituximab in rheumatoid arthritis]

SZEKANECZ Zoltán

MARCH 20, 2007

Hungarian Immunology - 2007;6(03)

[The therapy of rheumatoid arthritis (RA) is not always easy. Classical disease-modifying drugs are ineffective in about 10-15% of the cases. Furthermore, biologic agents, mainly tumor necrosis factor- α (TNF-α) inhibitors, may also be ineffective. Rituximab (RTX) is a B cell-inhibitory monoclonal antibody, which has been registered for the treatment of RA patients refractory to classical immunosuppressive agents including a TNF antagonist. Here we summarize the history of RTX therapy in RA including the presentation of the three major randomized clinical trials. We discuss the efficacy, safety of RTX, the practical points of RTX therapy, as well as some special considerations. The presented data suggest that RTX is a highly effective and safe biological, which can be used upon the inefficacy of any TNF inhibitor. RTX suppresses RA-associated inflammation, symptoms and decreases radiological progression. It may improve the functional capacity and quality of life of RA patients.]

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Hungarian Immunology

[The importance of etanercept treatment in rheumatology]

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[Rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis and psoriatic arthritis are inflammatory rheumatic conditions of unknown origin. Common characteristic features of these disorders include a relatively high prevalence, poorly understood pathogenesis and an unresolved treatment as well as a significant impact on mortality, morbidity and medical expenditures. The recognition of the central role of TNF-α in immune mediated inflammatory conditions, mainly in rheumatoid arthritis has led to the introduction of TNF-α blocking biological therapy into clinical rheumatology revolutionizing the management of these diseases. Etanercept is a human soluble TNF-α receptor attached to human IgG capable of effectively neutralizing TNF-α and lymphotoxin alpha. Since its introduction in 1998 as the first biological agent approved for RA, several clinical trials as well as everyday practice have proven its efficacy and safety. To date approximately 440 thousand patients, mostly with inflammatory rheumatic diseases have been treated with etanercept. In the present paper the pathophysiological role of TNF-α, the results of clinical trials of etanercept and its cost-effectivenes as well as issues regarding the use of etanercept in Hungary are reviewed.]

Hungarian Immunology

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[INTRODUCTION - Here we describe the case of the first Hungarian rheumatoid arthritis (RA) patient treated with RTX. CASE REPORT - This multiresistant patient had received numerous immunosuppressive drugs and all three anti-TNF agents had been tried. These biologicals had to be stopped due to inefficacy or side effects. RTX treatment resulted in some subjective clinical improvement, as well as a decrease in rheumatoid factor and anti-CCP production. Clinical activity assessed by DAS28 fell after 18 weeks. B cells disappeared from the circulation, however, the percentage of activated T cells increased. We observed initial B cell recovery after 18 weeks. CONCLUSION - Clinical studies suggest that RTX is more effective right after the failure of the first TNF inhibitor. Efficacy of RTX in this patient suggests that this drug may also be effective in a multiresistant patient, who had tried numerous TNF blockers.]

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Lege Artis Medicinae

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[INTRODUCTION - Survival data for rheumatoid arthritis (RA) have improved during the past years. Due to longer life expectancy, more attention has to be paid to prevention and treatment of long-term sequelae, including secondary malignancies. Incidence of malignant lymphoproliferative diseases and bronchial cancer is higher in a number of rheumatic diseases including RA. Some drugs nowadays very rarely used in RA - primarily cyclophosphamide and azathioprine - may further increase cancer risk. According to several large meta-analyses, biological therapy may also increase the risk of lymphomas, however, as these agents are used for the treatment of active, refractory arthritis, benefit may override such risks. PATIENTS AND METHODS - Altogether 516 RA patients managed at our department were assessed for the incidence and type of secondary malignancies. Although the absolute number of RA patients with a tumor was relatively small, we compared our cohort to the Health for All database and calculated standard incidence ratios (SIR). RESULTS - We identified 13 cases of malignancy (11 females and 2 males) in 516 RA patients (2.5%). In two patients, cancer developed before the onset of RA. RA patients with malignancy had an even higher female predominance (5.5 to 1) than usual. Mean age at onset of RA was 51.4 years, while age at the diagnosis of malignancy was 61.8 years. Mean duration of RA at the time of cancer diagnosis was 11.2 years. Five patients died, 4 due to the underlying malignancy. In the fifth patient, the tumor was considered cured but the patient died of amyloidosis. Among the 8 surviving patients, mean survival is 7.3 years until now, while overall survival of all 13 cancer patients is 4.7 years. Regarding types of malignancies, there were 6 cases of bronchial cancer, 2 cases of follicular thyroid cancer, and one cutaneous B cell lymphoma, one breast cancer, one gall bladder cancer, one colorectal cancer, and one pancreatic cancer. In comparison to the Health for All database, the overall SIR of all malignancies in RA was 1.12 (CI 0,91-1,33), varying between 2.2 and 70.7 among different tumor types. Only one cancer patient received cyclophosphamide therapy and some received methotrexate or anti-TNF agents. CONCLUSION - We identified 13 cases of malignancy among our RA patients. In RA, secondary tumors including bronchial cancer and lymphomas are more common than in the general population. Adequate treatment and monitoring of these patients may help us to lower the risk of malignancies secondary to RA]

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