Early treatment with a combination of immunosuppressant medications may be effective and safe for older patients with Crohn’s disease, as much as it is for younger patients, data from a clinical trial suggest.
This approach may be considered as a safe alternative for treating some older patients with Crohn’s disease, rather than long-term repeated use of steroids.
The findings appear in the study “Early combined immunosuppression may be effective and safe in older patients with Crohn’s disease: post hoc analysis of REACT,” which was published in the journal Alimentary Pharmacology and Therapeutics.
Combining medications that reduce the activity of the immune system, known as immunosuppressants, has proven successful at controlling or reducing symptoms in young patients with Crohn’s disease at high risk of complications.
Usually, these regimens combine anti-metabolites (e.g. methotrexate, azathioprine) with anti-TNF alpha biological medications (e.g. adalimumab, brand name Humira).
However, in older patients, who can be at higher risk of treatment-related complications, those drug combinations have been avoided because of safety concerns. A major worry with the use of combined immunosuppression in older adults is the risk of serious infections.
However, there is not enough scientific evidence to support or reject this concern in this particular patient group. A group of researchers sought to address the question by re-analyzing data from a prior clinical study they had carried out.
The trial REACT (NCT01030809) was designed to evaluate the efficacy of a treatment algorithm that encouraged earlier use of immunosuppressive medications versus conventional treatment for patients with Crohn’s disease.
Immunosuppressant combination therapy included anti-TNF alpha agent Humira (adalimumab) and anti-metabolites azathioprine and methotrexate.
A first analysis of this study demonstrated that early use of immunosuppressants was not superior to usual management for controlling disease symptoms (remission), but it did reduce the risk of adverse outcomes such as surgery, hospital admission, or serious disease-related complications.
In the current study, researchers re-analyzed the data to compare efficacy and safety results between younger (under 60) and older patients (60 and up).
Among the 1,981 patients enrolled, 311 were in the older group; 173 of those were assigned to early combined immunosuppression and 138 to conventional management.
Throughout the 24 months of the study, 10% of the older patients had disease-related complications — 6.4% of those receiving early combined immunosuppression and 14.5% of those getting standard treatment. The combined immunosuppression was equally effective for younger and older patients.
There was no significant difference between age groups in the proportion of those who achieved corticosteroid-free clinical remission or in reducing patients’ risk for a surgery, hospitalization or a serious disease complication.
Among younger patients, 72.6% achieved remission in the early immunosuppression group versus 64.4% in the conventional treatment group.
Similarly, with the older patients, remission was observed for 74.8% and 63.0%, respectively.
Also, there were no differences in the number of drug-related adverse events in older patients given combined immunosuppressants, even though “treatment-related harm could not be adequately assessed in this analysis,” researchers said.
As expected, a greater percentage of deaths occurred in older patients, (14 out of 311, 4.5%) than in younger patients (3 out of 1,670, 0.2%) but this proportion did not seem to be affected by whether patients were receiving the immunosuppression regimen or conventional treatment.
“It is important to treat aggressive Crohn’s disease appropriately regardless of age,” Siddharth Singh, MD, professor at the University of California San Diego and the study leader, said in a press release.
“This may include early step-up combination therapy of tumor necrosis factor-alpha antagonists with thiopurines [e.g. azathioprine], which is effective and safe even in older patients, rather than treating these patients with chronic or repeated courses of corticosteroids,” he said.
Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn’s disease with suboptimal disease control. But researchers cautioned that so far these results “should be considered exploratory and interpreted with caution,” and await confirmation in future studies focusing on older patients.