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Rituximab for rheumatoid arthrits treatment: a systematic review

Revista Brasileira de Reumatologia (English Edition), Volume 54, Issue 3, May–June 2014, Pages 220 - 230

Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti-TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases.

Methods

We conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti-TNF agents before, and to relate outcome with RF and anti-CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta-analysis.

Results

We included six RCTs comparing rituximab 1000 mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti-TNF treatment failure patients - ACR20/50/70 and EULAR response. We observed lower changes in Total Genant-modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF-36, FACIT-T and HAQ-DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti-CCP seropositive patients achieved ACR20 than RF/anti-CP negative patients in rituximab group.

Conclusion

Available data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti-TNF treatment failure patients. RF and anti-CCP seam to influence treatment results, but this inference needs further research.

Resumo

Introdução

A artrite reumatoide (AR) é uma doença autoimune crônica caracterizada por inflamação articular sistêmica que, com frequência, leva a significativa incapacitação. Vários agentes anti-TNF têm sido usados efetivamente, mas alguns pacientes demonstraram resposta inadequada. Rituximabe é um anticorpo monoclonal terapêutico indicado em tais casos.

Métodos

Realizou-se uma revisão sistemática para avaliar a eficácia e a segurança de rituximabe em pacientes com AR ativa previamente tratados ou não com agentes anti-TNF e para relacionar o desfecho com a sorologia para FR e anti-CCP. Pesquisaram-se importantes bancos de dados eletrônicos e a literatura não convencional, além de se fazer uma busca manual de referências. Para a meta-análise, utilizou-se o programa Review Manager® 5.1.

Resultados

Consideramos seis ERCs comparando rituximabe 1000 mg com placebo. Em ambos os grupos usou-se Metotrexato. O tratamento com rituximabe foi mais efetivo em pacientes jamais tratados e nos que não obtiveram sucesso com a terapia anti-TNF – critérios ACR 20/50/70 e EULAR. No grupo de rituximabe, observaram-se mudanças menos expressivas nos escores de Sharp/Genant, de erosão e de estreitamento do espaço articular; nesse grupo, os escores SF-36, FACIT-T e HAQ-DI também foram melhores. Não foram notadas diferenças entre grupos com relação aos desfechos de segurança, com exceção das reações agudas à infusão, que foram mais comuns no grupo de rituximabe. Ainda no grupo de rituximabe, um número maior de pacientes soropositivos para FR/anti-CCP alcançou ACR20, em comparação com pacientes negativos para RF/anti-CCP.

Conclusão

Os dados disponíveis falam em favor do uso de rituximabe para o tratamento da AR, como opção efetiva e segura para pacientes jamais tratados ou que não obtiveram sucesso com o tratamento anti-TNF. FR e anti-CCP parecem influenciar os resultados do tratamento, mas essa inferência ainda está à espera de futuras pesquisas.

Keywords: Rheumatoid arthritis, Rituximab, Systematic review, Safety, Efficacy.

Palavras-chave: Artrite reumatoide, Rituximabe, Revisão sistemática Segurança, Eficácia.

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Footnotes

a Department of Social Pharmaceutics, Pharmacy Faculty, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

b Department of Preventive and Social Medicine, Medicine Faculty, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

c Center of Research René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil

d Department of Locomotor Apparatus, Medicine Faculty, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Corresponding author.