Dose-interval of adalimumab might be prolonged in CD patients in stable remission

According to the results of an open-label trial, prolonging the dose interval from 2 to 3 and then to 4 weeks is possible in patients with Crohn’s disease (CD) in stable remission. This approach results in a similar rate of persistent flares and lower infection-related adverse events, but an increase in rescue medication use.

According to a retrospective study, dose de-escalation of adalimumab is possible in patients with CD [1]. One possible way of achieving this is simply increasing the dose interval. Possible advantages of this approach are decreasing adverse events linked to biological therapy. Cost-savings are another important advantage of a longer dose interval: “There are not only side effects for the patient, but also for society, because we know that with an increasing uptake of biologics, healthcare costs are rising rapidly,” Dr Reinier van Linschoten (Franciscus Gasthuis en Vlietland, the Netherlands) explained. An open-label, multicentre, randomised-controlled, non-inferiority LADI trial (NCT03172377) assessed the clinical outcomes of an increased adalimumab dose interval compared with conventional dosing in CD patients in stable remission [2]. All 174 participants were in steroid-free clinical remission while on adalimumab maintenance therapy (40 mg adalimumab, every other week, for at least 9 months). Participants were randomised to increase adalimumab dose interval from 2 to 3 and then to 4 weeks (n=113), or to continue the conventional dose interval of 2 weeks (n=61). The primary study endpoint was the incidence of persistent flares.

“A dose extension was possible in most of the patients in the intervention group, only 10% had to go back to the conventional dose interval,” Dr van Linschoten explained. Four patients in the intervention group and 1 patient in the control group were excluded from the analysis for not meeting the inclusion criteria. The cumulative incidence of persistent flares at week 48 in the intervention group (3/109) was non-inferior compared with the control group (0/60). In addition, the cumulative incidence of transient flares was similar between the groups (pooled adjusted risk difference [paRD] 2.68%; 95% CI -0.93–6.30; see Figure). At week 48, 92% of the control group and 72% of the intervention group were in clinical remission (paRD -16.3%; 95% CI -30.9 to -1.82). Neither disease activity nor quality-of-life significantly differed between the control and the intervention group. However, the intervention group used significantly more rescue mediation. Participants in the intervention group showed an increase in GI disorders, mainly mild GI side effects. A difference was also noted regarding the infection-associated adverse events: Per 100 person-years, 60 infection-related adverse events occurred in the intervention group versus 75 in the control group.

Figure: Disadvantages of a longer dose interval are an increase in escape medication and fewer patients in clinical remission [2]

“Increasing the adalimumab dose interval is a possible treatment strategy. However, there are some negative consequences like an increase in escape medication and fewer patients in clinical remission at week 48,” Dr van Linschoten concluded. Therefore, this approach should be discussed individually with the patient.

1. Van Steenbergen S, et al. Aliment Pharmacol Ther. 2017;45:923–932.
2. Van Linschoten RCA, et al. Clinical outcomes of increased versus conventional adalimumab dose inervals in patients with Crohn´s disease in stable remission. OP106, UEG Week 2022, 8–11 October, Vienna, Austria.

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Posted on 1 December, 2022