Abstract and Introduction
Abstract
Objective. Using meta-analysis methods, this study aimed to estimate the impact of biologic agents on physical function in patients with RA.
Methods. A systematic literature search was conducted independently by two investigators. Double-blind randomized controlled trials (RCTs) investigating the efficacy of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab or rituximab in approved dosages in comparison with treatment with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) and placebo were included. The outcome parameter was improvement in function measured by the standardized mean difference (SMD) of HAQ scores. The SMD is the difference of the change in HAQ between biologic and DMARD comparator groups divided by the pooled standard deviation. Mixed effect models were applied separately for RCTs with DMARD-naive patients and those with DMARD inadequate responders (IRs).
Results. Thirty-five RCTs were included in the analysis, 10 with DMARD-naive patients and 25 with DMARD IRs. Overall, biologics led to a greater improvement of physical function than nbDMARDs, with an SMD of the HAQ of 0.44 (95% CI 0.38, 0.50). The improvement was greater for DMARD IRs (SMD 0.48, 95% CI 0.41, 0.56) than for DMARD-naïve patients (SMD 0.32, 95% CI 0.23, 0.41). There were no significant differences between individual biologics in both groups.
Conclusion. Treatment with biologics led to a clinically relevant greater improvement in physical function than treatment with nbDMARDs. Our results suggest that the improvement found on the group level was caused by a clinically relevant improvement on the patient level in more than 50% of the patients.
Introduction
RA is a systemic autoimmune disease with a prevalence of ~1% in western countries. The disease causes inflammation and pain, and may lead to a serious loss of functional capacity. In recent years, new options for the treatment of RA have emerged. These new biologically engineered drugs have been shown to be effective and have the potential to change the course of disease for many patients. While some inhibit inflammatory response by blocking TNF-α, others influence the immune system via different pathways. They all have in common that they offer effective treatment options for patients who have active disease despite taking non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) like MTX.
Functional capacity is an important patient-reported outcome. The HAQ measures functional capacity and is used in most randomized clinical trials (RCTs). It is not only correlated with the risk of being permanently disabled, but also with an elevated risk of mortality. Effects on the independence of patients are substantial: a study from Westhoff et al. showed that more than 50% of patients with an HAQ >1.54 are in need of help. Therefore this analysis aims to investigate the magnitude of the benefits of biologic agents on the functional capacity of patients with RA.
Nineteen meta-analyses regarding the treatment of RA with different biologic agents were identified in a literature search. All of them assessed the efficacy of biologics using the response criteria from the ACR. These response criteria measure the percentage of improvement from baseline for a defined set of variables.
Three previous meta-analyses investigated the functional capacity measured by the HAQ. So far there is only one meta-analysis that included the HAQ as an outcome, accounted for baseline HAQ and compared inadequate responders (IRs) of nbDMARDs with DMARD-naive patients. It was restricted to the comparison of adalimumab, etanercept and infliximab. The following analyses also include abatacept, certolizumab, golimumab and rituximab.