Early Combined Immunosuppression may be Effective and Safe in Older Patients With Crohn's Disease

Post Hoc Analysis of REACT

Siddharth Singh; Larry W. Stitt; Guangyong Zou; Reena Khanna; Parambir S. Dulai; William J. Sandborn; Brian G. Feagan; Vipul Jairath

Disclosures

Aliment Pharmacol Ther. 2019;49(9):1188-119. 

In This Article

Abstract and Introduction

Abstract

Background: Physicians may be reluctant to prescribe combined immunosuppression in older patients with Crohn's disease due to perceived risk of treatment-related complications.

Aim: To evaluate the impact of age on risk of Crohn's disease-related complications in patients treated with early combined immunosuppression vs conventional management in a post hoc analysis of the randomised evaluation of an algorithm for Crohn's treatment (REACT), a cluster-randomised trial.

Methods: We compared efficacy (time to major adverse outcome of Crohn's disease-related surgery, hospitalisation or serious complications; corticosteroid-free clinical remission) and safety outcomes at 24 months, between patients aged <60 vs ≥60 years randomised to early combined immunosuppression or conventional management, using Cox proportional hazard analysis or modified Poisson model. In the early combined immunosuppression arm, patients with failure to achieve clinical remission within 4–12 weeks of corticosteroids were treated with a combination of tumour necrosis factor-α antagonist plus anti-metabolite and sequentially escalated in a stepwise algorithm.

Results: Of 1981 patients, 311 were ≥60 years (15.7%; 173 randomised to early combined immunosuppression and 138 to conventional management). Over 24 months, 10% of older patients developed Crohn's disease-related complications (early combined immunosuppression vs conventional management: 6.4% vs 14.5%) and 14 patients died (3.5% vs 5.8%). There was no difference between younger and older patients in risk of achieving corticosteroid-free clinical remission (<60 years, early combined immunosuppression (72.6%) vs conventional management (64.4%): relative risk [RR], 1.06 [95% CI, 0.98-1.15] vs ≥60 years, early combined immunosuppression (74.8%) vs conventional management (63.0%): RR, 1.09 [0.90-1.33], P-interaction = 0.78) or time to major adverse outcome (<60 years: hazard ratio [HR], 0.71 [0.53-0.96] vs ≥60 years: HR, 0.69 [0.31-1.51], P-interaction = 0.92) with early combined immunosuppression vs conventional management.

Conclusions: We observed no difference in efficacy and safety of early combined immunosuppression compared to conventional management in older and younger patients. Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn's disease with suboptimal disease control. Clinical Trial Identifier: NCT01030809.

Introduction

Approximately 10%-30% patients with IBD are older than 60 years, and with an aging population and chronic nature of IBD, the prevalence of IBD in older adults is anticipated to continuously rise.[1,2] Based on the 2015 National Health Interview Survey, an estimated 1.7% adults ≥65 years (approximately 805 000) reported a diagnosis of IBD.[3] Several cross-sectional studies and European registries have reported differences in disease phenotype and behaviour in older and younger patients with IBD.[4–7] While older patients may have less aggressive behaviour, they are more likely to be hospitalised and have similar rate of surgical intervention compared to younger patients. In a nationally representative longitudinal study of hospitalised adults, we observed that older patients with IBD have higher annual burden and costs of hospitalisation, and higher in-hospital mortality, as compared to younger patients.[8]

Since older patients comprise <5% of participants in clinical trials, evidence base to guide treatment strategies in this cohort is limited, with real-life practice trends towards long-term corticosteroid use and limited use of steroid-sparing agents.[9–11] Due to systematic differences between older vs younger patients in risks of disease-related complications, treatment-related complications and extra-intestinal complications (eg cardiovascular disease, malignancy), there is limited understanding of risk-benefit trade-offs of different therapies and treatment strategies. In younger patients at high risk of disease complications and relative paucity of concomitant comorbidity, aggressive therapy with combination of biologics and anti-metabolites is preferred.[12] However it is unclear whether this strategy can be directly extrapolated to older patients who may be more susceptible to treatment-related complications and non-Crohn's disease-related complications associated with comorbidity.

In an attempt to address this question, we performed a post hoc analysis of Randomised evaluation of an algorithm for Crohn's treatment (REACT) trial, a cluster-randomised trial comparing early combined immunosuppression vs conventional management in patients with Crohn's disease.[13] Specifically, we compared efficacy and safety outcomes between younger (<60 years) and older patients (≥60 years) with Crohn's disease.

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