Higher induction regimens (HIR) were not superior to standard induction regimens (SIR) for the treatment of Crohn disease (CD), according to results of a phase 3, randomized, double-blind, multicenter trial, published in Gastroenterology.

The Study of a novEl appRoach to induction and maintenance dosing with adalimumab in patiENts with moderate to severe Crohn Disease (SERENE CD) was conducted at 93 sites in 19 countries (ClinicalTrials.gov Identifier: NCT02065570). Patients (N=514) with moderate to severe CD were randomly assigned in a 3:2 ratio to receive HIR (n=308) or SIR (n=206). HIR consisted of 160 mg adalimumab for 3 weeks followed by 40 mg every other week (eow) adalimumab through week 12; SIR consisted of 160 mg adalimumab at baseline, placebo at weeks 1 and 3, and 80 mg adalimumab at week 2 followed by 40 mg eow adalimumab.

At week 12, patients who achieved clinical response (n=184) were randomly assigned in a 1:1 ratio to continue adalimumab maintenance clinically adjusted (CA) by C-reactive protein and Crohn Disease Activity Index (CDAI) score (n=92) or receive therapeutic drug monitoring (TDM) by serum adalimumab concentration and clinical criteria maintenance therapy (n=92) for 44 weeks. Safety and efficacy were assessed.


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The HIR and SIR cohorts were 51.3% and 52.9% women, aged median 34 (IQR, 18-73) and 34 (IQR, 18-71) years, 93.8% and 88.3% were White, 17.2% and 17.5% had previous infliximab use, and 50.3% and 48.5% used corticosteroids, respectively.

At week 12, clinical remission (62.3% vs 51.5%; P =.008), clinical response (83.4% vs 74.8%; P =.015), and change in CDAI score (mean change from baseline, -169.1 vs -149.5 points; P =.006) differed significantly between induction regimens, favoring HIR. Similar outcomes among patient groups were observed for endoscopic response and steroid-free remission.

Stratified by disease location, significantly more patients in the HIR group who had only ileal disease achieved endoscopic response at week 12 (40.0% vs 19.0%; P =.015) and no difference was observed for those with only colonic disease (42.7% vs 37.0%; P =.407), respectively.

During induction, 60.1% of HIR and 64.6% of SIR recipients had a treatment-emergent adverse event and 5.5% and 6.3% experienced a severe event, respectively.

The efficacy endpoints did not differ between cohorts at week 56 for the maintenance phase of the study, with the CA and TDM cohorts achieving clinical remission (53.8% vs 55.6%; P =.789), endoscopic response (34.6% vs 25.0%; P =.501), and endoscopic remission (23.1% vs 19.4%; P =.966) in similar amounts, respectively.

During the maintenance phase of the trial, 70.6% of the CA and 69.7% of the TDM recipients reported treatment-emergent adverse events; 6.4% and 5.5% experienced a severe event, and 7.3% and 8.3% of the cohorts discontinued the study drug due to an adverse event, respectively. The most common events were headache, worsening CD, nasopharyngitis, arthralgia, nausea, and dizziness.

This study may have been limited by not including a placebo control group.

The results of this study did not support a higher induction strategy of adalimumab for the treatment of moderate to severe CD and found that CA and TDM maintenance strategies were similarly effective.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

D’Haens GR, Sandborn WJ, Loftus EV, et al. Higher vs standard adalimumab induction dosing regimens and 2 maintenance strategies: randomized SERENE CD trial results. Gastroenterol. Published online February 2, 2022. doi:10.1053/j.gastro.2022.01.044