New Research Assesses Factors That May Impact Adalimumab Therapy in IBD

During this week’s 14th Congress of the European Crohn’s and Colitis Organisation, multiple research teams reported on efforts to better understand the factors that impact adalimumab therapy in patients with inflammatory bowel disease (IBD).

Early Adalimumab May Be Best for CD

First, investigators who conducted a large retrospective study of patients with Crohn disease (CD) reported on their attempt to evaluate primary nonresponse (PNR) to adalimumab, treatment persistence, and any factors that may be associated with PNR and persistence.

The study included 405 patients with CD who were treated between 2012 and 2017 at 3 centers in France. All patients received full adalimumab induction. In total, 34% had previously received infliximab, and had discontinued because of PNR, loss of response, intolerance, or other reasons.

Median time receiving adalimumab was 1.7 years (interquartile range, 0.7-3.6). In total, 9% of patients had PNR, while 91% maintained scheduled treatment. Drug survival rates for adalimumab 76% at 12 months, 59% at 24 months, and 51% at 36 months.

Two independent predictors of adalimumab failure were identified in a multivariate Cox regression: disease duration of 2 years or more (hazard ratio [HR], 3.16; 95% CI, 1.15-1.85; P = .02) and previous infliximab therapy (HR, 2.38; 95% CI, 1.09-2.57; P = .017).

“Patients with early CD, naive of [anti—tumor necrosis factor] treatments exhibited the best profile to response to adalimumab treatment. Awaiting results from disease modifications trials, these results suggest the clear benefit of introducing biologics early in the disease history,” concluded the authors.

High BMI Does Not Impact Response to Adalimumab

High body mass index (BMI) has been linked with poorer response to biologic therapy in patients with a variety of autoimmune diseases, but data related to the impact of high BMI on non—weight-based therapies, such as adalimumab, have been conflicting. However, researchers from a single center in Greece found that BMI does not impact treatment response to adalimumab in patients with moderately active CD.²

The study included 49 patients who were followed over a period of 2 years. The primary end point of the study was clinical, biological, and endoscopic remission at 24 weeks after initiating adalimumab at a dose of 40 mg every 2 weeks after induction. The mean BMI among patients was 27.13 (range, 19-41).

In total, 67.3% of patients achieved clinical and biological remission, and 59.1% achieved mucosal healing. Patients classified as having obesity, or a BMI over 30, had similar rates of remission as patients without obesity.

“We did not observe any correlation of any BMI cut-off value with clinical, biological, and endoscopic remission,” write the authors.

No Link Between High Serum Levels and Adverse Events

Finally, a research team reported on a study that sought to determine whether high serum adalimumab concentration increases the risk of adverse events (AEs) in patients with IBD.³

The retrospective study included 133 patients with IBD who had at least 1 measurement of serum adalimumab available. The cohort was divided according to the median adalimumab level, 9.8 μg/ml.

In total, 27 AEs were reported. In the 66 patients with higher adalimumab levels, 17 AEs were reported. In the 67 patients with lower adalimumab levels, 10 AEs were reported. The difference between groups was significant, and stratification of the patients into tertiles by adalimumab levels did not show any difference in the rates of AEs among groups, either.

The authors concluded that there does not appear to be an increased risk of AEs for patients with IBD who have higher serum levels of adalimumab.

References

1. Fumery M, Duveau N, Perignon C, et al. Prognostic factors for long-term adalimumab treatment. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P323. ecco-ibd.eu/publications/congress-abstract-s/abstracts-2019/item/p323-prognostic-factors-for-long-term-adalimumab-treatment.html.

2. Soufleris K, Fasoulas K, Kafalis N, Lazaraki G, Tzilves D. Body mass has no effect on treatment response in Crohn’s disease patients with moderate disease activity who receive adalimumab. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P329. ecco-ibd.eu/publications/congress-abstract-s/item/p392-body-mass-index-has-no-effect-on-treatment-response-in-crohn-0039-s-disease-patients-with-moderate-disease-activity-who-receive-adalimumab.html.

3. Narula N, Lauzon B, Marchall J. Higher adalimumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P607. ecco-ibd.eu/publications/congress-abstract-s/item/p607-higher-adalimumab-serum-levels-do-not-increase-the-risk-of-adverse-events-in-patients-with-inflammatory-bowel-disease.html.