Safety of Biologic Therapy in Older Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

Abstract

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e108. Learning Objective-Upon completion of this activity, successful learners will be able to define the diagnosis, natural history, and treatment of IBD in older individuals. BACKGROUND & AIMS: Management of immune-mediated inflammatory diseases often requires lifelong immunosuppression. Increasing numbers of older patients have inflammatory diseases and are particularly vulnerable to risks of immune suppressive therapies-particularly infections and malignancies. METHODS: We systematically searched PubMed/Medline and Embase to identify eligible studies that examined the safety of biologic therapies in older patients with immune-mediated inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis, psoriasis). Included studies provided information on patients who began receiving therapy with a biologic agent when they were older than 60 years and a control population (either younger users of biologics or older patients who did not use biologics). Information of on overall pooled rates of infections, malignancy, and mortality were extracted. A DerSimonian and Laird random effects model was used to calculate pooled odds ratios (ORs) and 95% CIs. RESULTS: Our meta-analysis included 14 unique studies that comprised 4719 older users of biologics, 13,305 younger users of biologics, and 3961 older patients who did not use biologics. The pooled prevalence of infections in older and younger users of biologics was 13% and 6% respectively, yielding a pooled random effects odds ratio of 2.28 (95% CI, 1.57-3.31). Older age was associated with a significant increase in risk of malignancy (OR, 3.07; 95% CI, 1.98-4.62) compared to younger age. Older users of biologics had a 3-fold increase in risk of infection compared to patients who did not use biologics (OR, 3.60; 95% CI, 1.62-8.01), but there were no significant differences in odds of malignancy (0.54, 95% CI, 0.28-1.05) or death (OR, 1.52; 95% CI, 0.44-5.28) compared to older patients who did not use biologics. CONCLUSION: In a systematic review and meta-analysis of studies on the safety of biologic therapies in older patients with inflammatory diseases, we found that older users of biologic agents have an increased risk of infections compared with younger users or older patients who do not use biologics. Large, prospective cohort studies are needed to examine safety of biologic therapy in older patients with immune-mediated diseases

Systematic review with meta‐analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease

“…This result is in contrast with a recent meta‐analysis by Borren et al that has reported a more than 10‐fold higher risk. However, we have included five studies for this outcome, while Borren et al included only three studies (two of them were case‐control studies showing inflated effect estimates), thus we are confident that we have synthesised the current evidence.…”

“…The results of the current study are relatively reassuring to clinicians willing to administer biologic drugs to their patients as compared to previous studies on the topic that had found a very elevated risk of infections in elderly IBD patients exposed to biologics . However, clinicians should take into account that sparse evidence showed that the risk of serious and opportunistic infections in older patients may increase further with combination therapy (ie biologics and thiopurines, or biologics thiopurines and corticosteroids) .…”

“…Several observational studies, and a meta‐analysis, have compared the risk in elderly IBD patients exposed to biologics with the risk in younger IBD patients exposed to such drugs, publishing highly significant results . However, these studies do not answer the most meaningful question (ie what are the risks of biologic therapies in elderly IBD patients as compared to administering other nonbiologic treatments).…”

“…Despite these limitations, we believe that our work has significant merits. We have conducted a rigorous and extensive literature search to collect all the eligible publications, and we were able to identify and analyse more than double the studies of a very recent meta‐analysis on a similar topic . Two independent reviewers have carefully undertaken the data extraction, and discrepancies were checked and resolved through consensus.…”

“…Some studies have estimated the risk of infections and malignancies in elderly people with IBD exposed to biologic agents by using not clinically meaningful comparison groups (eg younger exposed patients), providing estimates that could be misinterpreted by clinicians . A recent meta‐analysis on the topic included only six studies of elderly patients treated with biologics compared with those unexposed . Thus, we conducted an updated systematic review and meta‐analysis of published studies to examine the risk of serious infections, opportunistic infections, tuberculosis, any infection and cancer in elderly IBD patients exposed to biologic treatments as compared to those unexposed to biologic treatments.…”