When are anti-adalimumab antibodies (AAAs) most likely to develop in Crohn’s disease (CD) patients and how closely are they linked with treatment response?
AAAs may arise earlier than previously thought and might explain primary non-response to adalimumab (ADA) in some patients.
Ungar B, Engel T, Yablecovitch D, et al. Prospective Observational Evaluation of Time Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study. Am J Gastroenterol 2018;113:890–98. https://www.nature.com/articles/s41395-018-0073-0
While it is known that a proportion of CD patients will develop AAAs, it is unclear when in the course of treatment this will typically occur and to what extent AAAs predict treatment response. In this study, Israeli researchers prospectively examined 98 CD patients initiating ADA treatment. They obtained serum samples at weeks 0, 2 and 14 and every 3 months subsequently for a median of 44 weeks and also measured clinical disease activity using the Harvey Bradshaw Index (HBI). To determine whether the timing of serum sampling affects test results, the researchers obtained serum samples at 3-day intervals between two ADA injections from a subgroup of 29 patients.
According to the results, 32% of patients developed AAAs. More than half of these patients developed AAAs by week 2 and 79% did so by week 14. Development of AAAs before week 14 was associated with a 5-fold increased risk of primary non-response to treatment, compared to patients without AAAs prior to 14 weeks (P=0.005).
The researchers contrasted these findings with prior data they published from a group of CD patients receiving infliximab (IFX), in which they found 52% developed antibodies to IFX (ATIs) during the first 12 months of treatment (Gut 2014;63(8):1258–64). They noted that while 58% of those who developed ATIs lost either primary or secondary response, AAAs were more predictive of loss of response to ADA, with 85% of those who developed AAAs experiencing poor clinical response (P=0.01). Combination therapy with an immunomodulator and ADA did not affect the likelihood of AAA development or treatment response. Serum drug and antibody levels did not differ based on the timing of serum sampling.
Study Design: Prospective observational
Funding: Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, and The Leona M and Harry B Helmsley Charitable Trust
Setting: Multicenter trial
Level of Evidence: 1b (Oxford Levels of Evidence)
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