Comparing Adalimumab, Etanercept and Infliximab in RA
Comparing Adalimumab, Etanercept and Infliximab in RA
Purpose To compare the effectiveness of anti-tumour necrosis factor (TNF) agents in biologically naive and 'switched' rheumatoid arthritis (RA) patients.
Methods RA patients enrolled in the CORRONA registry newly prescribed adalimumab (n=874), etanercept (n=640), or infliximab (n=728) were stratified based on previous anti-TNF use. Clinical effectiveness at 6, 12 and 24 months was examined using the modified American College of Rheumatology response criteria (mACR20/50/70) and achievement of remission (28-joint disease activity score (DAS28) and clinical disease activity index (CDAI)) in unadjusted and adjusted analyses. The persistence of anti-TNF treatment was examined using Cox proportional hazard models.
Results Among 2242 patients (1475 biologically naive, 767 switchers), mACR20, 50 and 70 responses were similar (p>0.05) for adalimumab, etanercept and infliximab at all time points, as were rates of CDAI and DAS28 remission (p>0.05). Response and remission outcomes were consistently inferior for switched versus biologically naive patients. The adjusted OR for achieving an mACR20 response was 0.54 (95% CI 0.38 to 0.76) in first-time switchers and 0.42 (95% CI 0.23 to 0.78) in second-time switchers versus biologically naive patients at 6 months. The adjusted OR for achieving DAS28 remission were 0.29 (95% CI 0.15 to 0.58) for first-time switchers and 0.26 (95% CI 0.08 to 0.84) for second-time switchers. Persistence was higher in biologically naive patients, for whom persistence was highest with infliximab.
Conclusions No differences in rates of drug response or remission were observed among the three anti-TNF. Infliximab was associated with greater persistence in biologically naive patients. Response, remission and persistence outcomes were diminished for patients who switched anti-TNF.
Over the past decade, anti-tumour necrosis factor (TNF) therapies have become the most frequently prescribed class of biological agents for the treatment of rheumatoid arthritis (RA) in the USA and Europe. Currently, there are five anti-TNF agents approved by the European Medicines Agency and the US Food and Drug Administration, with varying structures, dosing and pharmacokinetics. Despite these differences, they all block TNF, and two randomised clinical trial (RCT) meta-analyses of three commonly prescribed anti-TNF (adalimumab, etanercept and infliximab) concluded that the three anti-TNF demonstrated comparable efficacy. However, these meta-analyses have been criticised, and their findings conflict with the results reported in two European registry studies demonstrating that adalimumab and etanercept users have better clinical responses than infliximab users. Those reports originated from European countries with more restricted access to biological agents and dosage restrictions.
An important caveat to the application of anti-TNF RCT results to RA patients in the clinic is that the vast majority of the RCTs were conducted in biologically naive patients, particularly in those without a previous history of anti-TNF treatment. However, intraclass switching of anti-TNF agents is common in clinical practices in Europe and the USA. Currently, there is inadequate evidence regarding the benefits of this strategy. As a result, switching patients to a different anti-TNF agent is restricted in certain European countries. Comparative effectiveness research using observational data sources has gained broader support in Europe and the USA across clinical disease areas.
Comparative effectiveness studies using observational data from registries represent a promising alternative to RCT for comparing interventions and therapies between biologically naive patients and patients who switch anti-TNF. This is important because rheumatologists in the USA and many European countries prescribe anti-TNF agents to RA patients with markedly lower disease activity than RCT populations. Given that comparative effectiveness data for US-based cohorts are lacking, the aim of the present study was to compare the clinical effectiveness of specific anti-TNF agents and the strategy of intraclass switching in a large US cohort of RA patients using the Consortium of Rheumatology Researchers of North America (CORRONA) registry. In particular, we sought to compare composite rates of drug response and remission outcomes as well as the persistence of anti-TNF treatment over a 2-year period.
Abstract and Introduction
Abstract
Purpose To compare the effectiveness of anti-tumour necrosis factor (TNF) agents in biologically naive and 'switched' rheumatoid arthritis (RA) patients.
Methods RA patients enrolled in the CORRONA registry newly prescribed adalimumab (n=874), etanercept (n=640), or infliximab (n=728) were stratified based on previous anti-TNF use. Clinical effectiveness at 6, 12 and 24 months was examined using the modified American College of Rheumatology response criteria (mACR20/50/70) and achievement of remission (28-joint disease activity score (DAS28) and clinical disease activity index (CDAI)) in unadjusted and adjusted analyses. The persistence of anti-TNF treatment was examined using Cox proportional hazard models.
Results Among 2242 patients (1475 biologically naive, 767 switchers), mACR20, 50 and 70 responses were similar (p>0.05) for adalimumab, etanercept and infliximab at all time points, as were rates of CDAI and DAS28 remission (p>0.05). Response and remission outcomes were consistently inferior for switched versus biologically naive patients. The adjusted OR for achieving an mACR20 response was 0.54 (95% CI 0.38 to 0.76) in first-time switchers and 0.42 (95% CI 0.23 to 0.78) in second-time switchers versus biologically naive patients at 6 months. The adjusted OR for achieving DAS28 remission were 0.29 (95% CI 0.15 to 0.58) for first-time switchers and 0.26 (95% CI 0.08 to 0.84) for second-time switchers. Persistence was higher in biologically naive patients, for whom persistence was highest with infliximab.
Conclusions No differences in rates of drug response or remission were observed among the three anti-TNF. Infliximab was associated with greater persistence in biologically naive patients. Response, remission and persistence outcomes were diminished for patients who switched anti-TNF.
Introduction
Over the past decade, anti-tumour necrosis factor (TNF) therapies have become the most frequently prescribed class of biological agents for the treatment of rheumatoid arthritis (RA) in the USA and Europe. Currently, there are five anti-TNF agents approved by the European Medicines Agency and the US Food and Drug Administration, with varying structures, dosing and pharmacokinetics. Despite these differences, they all block TNF, and two randomised clinical trial (RCT) meta-analyses of three commonly prescribed anti-TNF (adalimumab, etanercept and infliximab) concluded that the three anti-TNF demonstrated comparable efficacy. However, these meta-analyses have been criticised, and their findings conflict with the results reported in two European registry studies demonstrating that adalimumab and etanercept users have better clinical responses than infliximab users. Those reports originated from European countries with more restricted access to biological agents and dosage restrictions.
An important caveat to the application of anti-TNF RCT results to RA patients in the clinic is that the vast majority of the RCTs were conducted in biologically naive patients, particularly in those without a previous history of anti-TNF treatment. However, intraclass switching of anti-TNF agents is common in clinical practices in Europe and the USA. Currently, there is inadequate evidence regarding the benefits of this strategy. As a result, switching patients to a different anti-TNF agent is restricted in certain European countries. Comparative effectiveness research using observational data sources has gained broader support in Europe and the USA across clinical disease areas.
Comparative effectiveness studies using observational data from registries represent a promising alternative to RCT for comparing interventions and therapies between biologically naive patients and patients who switch anti-TNF. This is important because rheumatologists in the USA and many European countries prescribe anti-TNF agents to RA patients with markedly lower disease activity than RCT populations. Given that comparative effectiveness data for US-based cohorts are lacking, the aim of the present study was to compare the clinical effectiveness of specific anti-TNF agents and the strategy of intraclass switching in a large US cohort of RA patients using the Consortium of Rheumatology Researchers of North America (CORRONA) registry. In particular, we sought to compare composite rates of drug response and remission outcomes as well as the persistence of anti-TNF treatment over a 2-year period.
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