july 2020 • BMJ

Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data

Janke Kirsten, Biester Katharina, Krause Dietmar, Richter Bernd, Schürmann Christoph, Hirsch Katharina, et al.

DOI: 10.1136/bmj.m2288

Content curated by:David Rodrigues

Key message

Qual a efectividade dos diferentes medicamentos biológicos no tratamento da artite reumatóide? Revisão sistemática e network meat-análise que tenta avaliar a eficácia e segurança do tratamento com biológicos em pessoas com artrite reumatóide após falha do metotrexato. No global, verifica-se semelhança na eficácia e segurança entre os medicamentos biológicos em combinação com o metotrexato. Faltam comparações directas entre as diferentes opções bem como dados a longo prazo.

Analysis

Population

Adultos com artrite reumatóide tratados com medicamentos biológicos em combinação com metotrexato após falha do metotrexato durante pelo menos 24 semanas.

Method

Revisão sistemática e network meta-análise (dados a nível individual). Incluiram dados de ensaios clínicos aleatorizados e controlados até 2017 com dados disponibilizados ao nível do indivíduo.

Results

Identificaram 45 estudos que cumpriam critérios de inclusão. Conseguiram fazer análises comparativas das várias combinações possíveis. No global encontraram não existir diferenças na eficácia e segurança entre as várias combinações. No campo da eficácia, anakinra foi o que demonstrou menos benefício e no campo da segurança, o certolizumab pegol foi o que apresentou mais efeitos adversos. Faltam dados a longo prazo.

Abstract

Objective To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes. Design Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data. Data sources Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017. Eligibility criteria for selecting studies Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks. Results 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included. Conclusions For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.