Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to Young: A systematic review and meta-analysis
Section snippets
Background
Rheumatoid arthritis (RA) is a chronic systemic inflammatory arthritis an average age of onset at 55 years [1]. About one-third of patients acquire the disease after the age of 60–65, conventionally classified as “late” or “elderly” onset RA. Given the chronic nature of the disease, average RA patients can expect to have the disease well into their senior years [2], [3]. In fact, the prevalence of RA in older population is twice of what is noted across all ages (app. 2% v. 1) [4], [5]. In
Methods
Search strategy: We formulated the research question using the PECOS format. The population was adult rheumatoid arthritis patients using biologics including tofacitinib, the exposure and comparison groups were old and young RA patients, outcomes were clinical efficacy and safety, and study designs included were randomized controlled trials (RCT) and observational trials (both cohort and case-control studies).
A systematic literature search was performed to identify studies indexed until April
Results
A total of 5353 articles were retrieved with the systematic search and after eliminating exact duplicates. After title/abstract screening and including 17 articles from references of prior review articles, 185 articles were included for full-text review; 32 studies fulfilled inclusion criteria (Fig.1). Eight articles focused on efficacy, 15 on safety and 9 on both. Among these, 22 articles (69%) focused on anti-TNF agents, 4 on tocilizumab, 2 on abatacept, 2 on tofacitinib, 1 on rituximab and 1
Baseline disease activity
Nine out of the 24 articles (37.5%) provided baseline disease activity in form of DAS-28, ESR, CRP or erosive disease by age group [44], [46], [51], [52], [53], [54], [55], [56], [57]. Baseline DAS28 was reported in each of these articles and was comparable between older and young RA groups (5.33 ± 0.48 vs. 5.08 ± 0.48, p = 0.35, n = 7 ) [46], [51], [52], [54], [55], [56], [57]. Baseline CRP was recorded only in 4 articles [46], [51], [52], [56], ESR in 5 [46], [51], [52], [54], [56] and
Efficacy outcomes (Tables 2a and 2b)
Most of the efficacy studies focused on anti-TNF agents (9/13, 69%), 2 each on abatacept and abatacept and 1 each on tocilizumab and rituximab. Across all studies, there was significant heterogeneity in reporting outcomes including the use of odds of remission by DAS28, odds of remission by EULAR response criteria, change in DAS28, ACR response criteria, EULAR response, change in HAQ-DI, change in CDAI and change in SDAI. Further, these were reported at different times of follow-up ranging from
Safety outcomes (Tables 2a and 2b)
Nineteen articles focussed on the safety of biologics; 12 (63%) of these focused on anti-TNF drugs, 3 on tocilizumab, 2 of tofacitinib, 1 each on abatacept and rituximab. Infection and serious infections were the focus of 16 articles (70%), 7 (29%) focused on ADR, 3 focused on malignancy and 2 on zoster.
8 studies of the 12 studies focussing on anti-TNF agents evaluated infections as an outcome; of these 2 (Bathon et al and Flieschmann et al) used the same underlying cohort. The study by Bathon
Discussion
This systematic review and meta-analysis identified 32 articles which compared the efficacy and safety outcomes in older and young RA patients. We noted significant heterogeneity in defining older RA patients and hence we focussed our primary analyses among studies which use 60–65years of age to define older RA population (24 studies). The majority of the included studies showed reduced efficacy and safety of biologics in older RA patients compared to young. Meta-analyses of studies focusing on
Conclusions
The current systematic review and meta-analyses shows a reduced benefit-to-risk ratio of biologic agents in the older RA population. However, this observed effect may be reflective of biases inherent to observational studies and reflective of the current clinical practices. Further, the non-intensification of RA therapy to include biological agents in older patients would lead to increased use of non-steroidal anti-inflammatory agents, glucocorticoids in combination with synthetic DMARDs which
Acknowledgment
We would like to acknowledge Barbara Davis for her assistance with developing a comprehensive search strategy.
Conflicts of interest
None.
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Funding: Internally funded; no external funding obtained.