From the Journals

Steroids show less effectiveness in older-onset UC


 

FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Intravenous steroids were less effective in ulcerative colitis patients with older-onset disease, compared with younger-onset patients, according to data from nearly 500 individuals.

A combination of rising ulcerative colitis rates and an aging population has driven an increase in older-onset UC worldwide, Shinji Okabayashi, MD, of Kyoto University, and colleagues wrote in a study published in Alimentary Pharmacology & Therapeutics.

Data on differences in disease history between younger- and older-onset cases have been inconsistent, but one meta-analysis suggested a higher rate of surgery in older-onset cases, the authors of the current study wrote. “The higher risk of surgery may be due to the difference in effectiveness of intravenous steroid treatment, which is one of the important treatment options to avoid surgery for a severe course of UC,” but data on the effectiveness of IV steroids for older-onset UC are lacking.

The researchers reviewed data from 467 adults with ulcerative colitis at 27 centers in Japan. The participants were hospitalized and received their initial intravenous steroids between April 2014 and July 2019. The treatment was a daily dose of 40 mg or more of IV prednisolone or its equivalent, with dosing according to current guidelines. The primary outcome was clinical remission after 30 days.

The study population included 83 patients with older-onset UC and 384 with younger-onset UC. No cutoff currently exists to classify UC by age; the researchers defined younger onset as patients diagnosed at younger than 60 years and older onset as those diagnosed at age 60 years and older. The median age of onset was 32 years in the younger-onset patients and 68 in the older-onset group.

Overall, 51.8% of older-onset patients and 65.6% of younger-onset patients had clinical remission at 30 days (adjusted risk ratio, 0.74; P = .009). The incidence of colectomy at 30 days was significantly higher in older-onset patients, compared with younger-onset patients (15.7% vs. 1.8%; P < .001).

The researchers also assessed risk of surgery and adverse events at 90 days as secondary outcomes. The risk of surgery was significantly higher in older-onset patients compared with younger-onset patients (20.5% vs. 3.1%; ARR, 8.92) as was the risk of adverse events (25.3% vs. 9.1%, ARR, 2.19). A total of four deaths occurred during the study period, all in older-onset patients.

In addition, the researchers found that clinical remission rates at 30 days in older patients with younger-onset UC was similar to that of younger patients with younger-onset UC.

Potential contributors to the lower effectiveness of intravenous steroids in older-onset UC include genetic susceptibility, gut microbiota, and environmental factors, the researchers noted. The dysregulated immune response in older-onset UC also might play a role in limiting the effectiveness of intravenous steroids in these patients.

The study findings were limited by several factors including the lack of data on genetic susceptibility, environmental factors, and gut microbiota, as well as the inclusion only of patients with moderate to severe disease, which might have contributed to the higher risk of surgery in older patients, the researchers said. Other potential limitations include the potential confounders of concomitant drugs and nutritional status, and the use of symptom-based scoring to determine clinical remission.

However, the overall results reflect data from a recent meta-analysis, and the current study “clearly suggests that one of the reasons for the poor prognosis in patients with older-onset UC is the lower effectiveness of intravenous steroid treatment, which is one of the important treatment options for a severe course of UC,” the researchers wrote.

“Further research is warranted to establish the optimal treatment strategies for moderate to severe older-onset UC,” they concluded.

Findings have value for high-risk patients

The study is of interest to clinicians in practice, Hamed Khalili, MD, of Massachusetts General Hospital, Boston, said in an interview. “The findings are largely consistent with prior studies that have shown older-onset IBD patients have higher risk of surgery,” said Dr. Khalili, who was not involved with the study.

“This study focuses on a smaller subset of patients with IBD who present with acute severe UC,” Dr. Khalili noted. “Since this is a higher-risk patient population, the findings that older-onset UC is associated with lower response to intravenous steroids could have direct clinical implications.”

The study was supported by the Japanese Society for Inflammatory Bowel Disease. The researchers had no relevant financial conflicts to disclose. Dr. Khalili had no financial conflicts to disclose.

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