Longer adalimumab dose intervals improve infection risk, worsen remission rates in Crohn’s
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Increasing adalimumab dose intervals reduced infection-related adverse events and costs in patients with Crohn’s disease, but also resulted in lower remission rates, researchers reported in The Lancet Gastroenterology & Hepatology.
“Patient’s living with Crohn’s disease often need lifelong medication,” Reinier C.A. van Linschoten, MD, of the department of gastroenterology and hepatology at Erasmus Medical Center in the Netherlands, told Healio. “Adalimumab is one of these treatments that is effective in inducing and maintaining remission. However, adalimumab is quite expensive and can lead to adverse effects, such as injection site reactions and increased incidence of infections.”
He continued, “We wanted to see if it is possible to reduce the dose of adalimumab (by extending the duration between doses) by assessing if it did not lead to more flares while at the same time reducing costs and adverse effects.”
Linschoten and colleagues conducted an open-label, multicenter study with 174 adult patients with luminal CD who were in steroid-free clinical and biochemical remission at enrollment. Before inclusion, all patients were on a biweekly, stable dose of subcutaneous adalimumab (40 mg).
Researchers randomly assigned 113 participants to the intervention group, who underwent increased adalimumab dose intervals of 40 mg every 3 weeks at baseline and further to every 4 weeks if they remained in clinical and biochemical remission at week 24. Sixty-one patients in the control group continued their biweekly dosing.
The primary outcome of interest was the cumulative incidence of persistent flares at week 48.
According to results, the cumulative incidence of persist flares at week 48 was noninferior among patients in the intervention group compared with the control group (3% vs. 0%; adjusted risk difference [aRD] = 1.86%; 90% CI, –0.35 to 4.07). Researchers noted, however, that patients in the intervention group were less likely to be in clinical and biochemical remission (72% vs. 92%; aRD = –16.1%; 95% CI, –31.3 to –0.91).
There were seven serious adverse events during the study, all of which were in the intervention group. Incidence rates of adverse events were 168.35 per 100 person-years and 134.67 per 100 person-years in the intervention and control groups, respectively, and included 59.99 vs. 75.03 per 100 person-years for infection-related events and 42.57 vs. 5.77 per 100 person-years for gastrointestinal events.
According to Linschoten, increasing the adalimumab dose interval to every 3 weeks and then every 4 weeks did not lead to more persistent disease flares, but it did reduce infections and injection-site reactions and health care costs. It also led to lower rates of clinical and biochemical remission after 48 weeks.
“Further steps are [needed] to assess the cost-effectiveness of increasing the dose interval, see which patients benefited most from the intervention and develop a prediction model by which these patients can be selected,” Linschoten told Healio.
“The intervention of increasing dose intervals can be discussed with patients who have side effects from adalimumab therapy or want to reduce biologic exposure for another reason. This should be done in a shared decision-making process, balancing the reduced risk of side effects against the slight increase of disease activity.”
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Van Linschoten RCA, et al. Lancet Gastroenterol Hepatol. 2023;doi:10.1016/S2468-1253(22)00434-4.
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