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

https://doi.org/10.1016/j.cgh.2018.12.032Get rights and content

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

Section snippets

Literature Search

We performed a systematic electronic search of the MEDLINE and Embase databases to identify eligible studies examining safety of biologic therapy in older patients with IMD. Our search encompassed articles published from the inception of MEDLINE and Embase up to June 2018. We did not apply any language restrictions but required at least the abstract to be available in English. Our search combined 4 different phrase groups by using the Boolean operator AND. The first phrase included terms to

Literature Search

Our initial literature search identified 756 relevant studies on MEDLINE or Embase from inception to June 2018. Upon review of title and abstract, 33 articles were selected for full-text review (Figure 1). Among these, 19 additional studies were excluded. Three studies had no detailed data available regarding safety outcomes,13, 14, 15 2 studies were not accessible in full-text,16, 17 and 1 study was excluded because it included fewer than 10 patients.18 Thirteen studies were excluded because

Discussion

The therapeutic armamentarium for chronic IMDs has considerably expanded with the introduction of more effective biologic therapies leading to improved patient outcomes. However, safety concerns, particularly risk of infection and malignancy, remain. A population that is particularly vulnerable to those risks yet underrepresented in cohorts and clinical trials, is the older patient. In this systematic review and meta-analysis, we quantify the risk of infection, malignancy, and mortality in

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    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.

    Conflicts of interest This author discloses the following: Ashwin N. Ananthakrishnan has served on advisory boards for Abbvie, Takeda, and Merck. He is supported by research funding from the Crohn’s and Colitis Foundation, National Institutes of Health, Chleck Family Foundation, and Pfizer. The other author discloses no conflicts.

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