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Is early combined immunosuppression safe for older patients with Crohn’s disease?

Crohn's disease

A new study compared the safety and effectiveness of early combined immunosuppression and conventional treatment in older patients with Crohn’s disease.

 

Crohn’s disease and ulcerative colitis are the two main subtypes of inflammatory bowel disease, a chronic inflammatory condition involving the gut. Inflammatory bowel disease was long believed to be a disease of the young. However, based on recent reports, 10-30% of inflammatory bowel disease patients are over the age of 60 who either develop the disease at an older age or have aged with the disease.

Conventional treatment versus early combined immunosuppression

The treatment of Crohn’s disease is focused on three main goals: inducing and maintaining remission, improving quality of life, and preventing disease-related complications to minimize adverse events.

The conventional treatment used for most patients with Crohn’s disease uses corticosteroids. Although conventional treatment approach helps control symptoms, with time patients become either resistant to or dependent on corticosteroids. In addition, exposure to corticosteroids for long periods of time is associated with an increased risk of mortality.

The other treatment approach for Crohn’s disease is the combined immunosuppressant therapy that uses a biologic agent such as anti-tumor necrosis factor and an immunosuppressive agent such as thiopurines.

Clinical challenges in diagnosis and treatment of Crohn’s disease in older patients

Many studies have examined the challenges in the management of Crohn’s disease. Diagnosis of Crohn’s disease can be difficult in older patients due to the complications associated with physical changes of ageing, associated comorbidities, and atypical presentations.

Adverse events have limited beneficial treatment options in the management of Crohn’s disease in older patients. In addition, the existence of multiple morbidities increases the complexity of therapy and use of multiple drugs in old age elevates the risk of drug interactions and treatment non-compliance. A lack of drug efficacy trials in older adults with Crohn’s disease further limits the physicians to try different treatment options.

Aggressive therapy of Crohn’s disease is preferred in young patients

The physicians successfully use a combination of biologics and anti-metabolites as aggressive therapy for Crohn’s disease in the younger population who is at risk of disease complications and occurrence of comorbidities. However, the safety and effectiveness of such aggressive therapy is not proven in the older population. Therefore, physicians prefer using conventional treatment with corticosteroids for older adults with Crohn’s disease.

New study evaluates safety and effectiveness of combined immunosuppression in older patients

A new study by the researchers in the University of California San Diego in the United States compared the effects of early combined immunosuppression and conventional treatment in older patients in a post hoc analysis of the randomized evaluation for Crohn’s treatment (REACT) trial. The findings were recently published in the journal Alimentary Pharmacology & Therapeutics.

The trial included 1981 patients, 311 of which were 60 years or older. The researchers evaluated the effect of age on the risk of adverse events associated with early combined immunosuppression compared with conventional management of Crohn’s disease. They randomly assigned 173 patients to early combined therapy and 138 patients to conventional therapy. The patients who failed to achieve clinical remission within 4-12 weeks of conventional treatment received combination therapy that included anti-tumor necrosis factor and an antimetabolite in a stepwise algorithm.

The researchers compared the occurrence of adverse events such as Crohn’s disease-related hospitalization, surgery or other complications, as well as measured safety outcomes between older (60 years and above) and younger patients.

The patients were followed up for 24 months. During this time, 10% of older patients developed Crohn’s-disease-related complications, which occurred at 6.4% in the combined treatment group and 14.5% in the conventional treatment group.

No difference between younger and older patients in the risk of achieving corticosteroid-free remission

The results showed that there was no difference in the effectiveness of early combined treatment based on anti-tumor necrosis factor between older and younger patients. Furthermore, the researchers observed no increase in the side effects of the treatment in older patients. Although a greater number of older patients died of Crohn’s disease compared to younger patients, there was no difference in the mortality rates between conventional and combined treatment groups of older patients.

The findings are applicable to a broad population

The main strength of the study is the post hoc analysis of a cluster randomized trial that makes these findings apply broadly. In addition, a long follow up period helped the researchers assess the risk of Crohn’s disease-related complications. Certain limitations of the disease include the exploratory nature of results, comparison of treatment strategies but not of specific medications, and failure to assess long-term effectiveness and safety of treatment strategies.

Early combined immunosuppression may be safely used for older patients with Crohn’s disease

The results of the analysis indicate that early combined immunosuppression therapy based on anti-tumor necrosis factor is as safe and effective in older patients as in younger patients.This treatment strategy can safely be used in older patients instead of treating them with chronic use of corticosteroids. The researchers suggest that future studies should focus on evaluating optimal treatment approaches in older patients who are at high risk of complications of Crohn’s disease.

Written by Preeti Paul, MS Biochemistry

Reference: Sidharth Singh et al., Early combined immunosuppression may be effective and safe in older patients with Crohn’s disease: post hoc analysis of REACT. Aliment Pharmacolther. 2019;1-7. DOI:10.1111/apt.15214

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