The introduction of biologic (b) disease-modifying antirheumatic drugs (DMARDs) into clinical practice has been a major advancement for patients with rheumatoid arthritis (RA) in whom treatment with conventional synthetic (cs)DMARDs has failed, and has contributed to the improved outcomes in RA reported over the previous two decades.[1,2] The short-term safety of bDMARDs has been documented in clinical trials; however, the long-term safety of bDMARDs is of clinical interest in the population of patients with RA. In particular, the risk of malignancies and hospitalized infections in patients with RA is higher than in the general population,[4,5] and there is a need to differentiate between the long-term effects of RA and those associated with bDMARD treatment. Additionally, most safety data in the literature relate to tumour necrosis factor-α inhibitors (TNFis), and more studies are needed relating to the safety of other bDMARDs and targeted synthetic DMARDs.
Abatacept is a fully human, selective T cell co-stimulation modulator that was approved in the USA for the treatment of RA in 2005. The efficacy of abatacept in RA in both biologic-naïve patients and in those with previous bDMARD failure has been demonstrated in several randomized controlled trials (RCTs).[6–15] The safety findings across these studies were consistent between trials, and integrated analyses reflecting the long-term safety of intravenous (IV) and subcutaneous (SC) abatacept reported similar and stable incidence rates (IRs) of serious infections (SIs), malignancies, autoimmune events and infusion reactions, with no new safety signals over time.[6–12,14–17] However, the relevance of these findings to the longer-term use of abatacept in clinical practice may be limited by the stringent patient inclusion criteria, short follow-up periods and limited power restraints for the detection of adverse events (AEs) in RCTs. Data from observational studies can supplement RCT safety data to broaden the understanding of the risks associated with abatacept treatment over time in a typically heterogeneous, clinical RA population. To date, observational findings for the safety of abatacept are mostly derived from biologic- or abatacept-specific registries of administrative or pharmacy data. Analyses of these data have generated conflicting results, possibly due to considerable variations in factors such as study population, comparators, outcome definitions, confounders and AEs.[18–25] Comparative observational data on the IRs of malignancies with abatacept are also inconsistent;[26,27] however, when compared with other bDMARDs, abatacept has been associated with a higher relative risk of non-melanoma skin cancers (NMSCs).[23,28] Comparative data for the risk of SIs with abatacept versus other bDMARDs are similarly conflicting,[19,20,22,25,29] and there are no data directly comparing the risk of SIs with abatacept versus csDMARDs.[19,25]
The abatacept global post-marketing epidemiology programme was designed to evaluate infection and malignancy risks associated with abatacept (initially intended as a first-line DMARD) compared with those of csDMARDs for the treatment of RA. The programme spanned more than 10 years and consists of observational studies based on biologic disease registries and healthcare claims databases, such as FORWARD (the National Databank for Rheumatic Diseases)—a US-wide registry that enrolls patients with rheumatic diseases in the community. Information from patients is obtained from questionnaires every 6 months and is validated when required using medical records.
The aim of this analysis was to assess the risks of malignancies, infections, autoimmune diseases and mortality in patients with RA treated with abatacept compared with other bDMARDs or csDMARDs in an observational cohort of patients enrolled in the US FORWARD registry.
Arthritis Res Ther. 2019;21(141) © 2019 BioMed Central, Ltd.
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