Subtherapeutic dosing occurs in one-half of patients on infliximab maintenance therapy for inflammatory bowel disease

Background In Australia, infliximab is used in patients with inflammatory bowel disease (IBD) at a maintenance dose of 5 mg/kg, given 8-weekly. Many patients do not achieve therapeutic blood drug levels (defined as≥5 mg/L). New precision dosing models have been shown to reduce non-response, adverse events, and health care costs.

Aim To determine if Australian patients treated with infliximab are currently dosed appropriately to achieve therapeutic drug levels.

Method Patients with IBD treated with 8-weekly maintenance infliximab therapy, dosed at 5mg/kg were included. A recorded infliximab dose was considered Dose X if the following was available: 3 previous infliximab doses given 8-weekly, albumin and C-reactive protein at time of Dose X, trough infliximab level immediately preceding dose X and the patient’s weight. The Baysient LLC iDOSE®​ software was then used to predict Dose X to maintain a therapeutic infliximab blood level of≥5 mg/L until the next 8-weekly dose. The predicted-Dose X was compared to the actual-Dose X given.

Results 180 patients (54% male) were included with 451 Dose X recordings. Most patients had Crohn’s disease (77%), then ulcerative colitis (18%) and the remainder IBD-unclassified. At the time of Dose X, median age was 36 (IQR 29-46) years with a disease duration of 8 (IQR 3-16) years, 69% were on immunomodulators and 5% were smokers. Time on infliximab before Dose X was 2 (IQR 0-4) years. Median trough infliximab level was 4.9 (IQR 2.5-7.5) mg/L, albumin was 38 (IQR 35-40) g/L, and C-reactive protein was 3 (IQR 3-5) mg/L. Comparing actual-Dose X with predicted-Dose X, 53% of patients were underdosed (400 vs 890mg) and 47% were adequately dosed (400 vs 220mg) to achieve therapeutic infliximab blood levels. The underdosing occurred by 5.6mg/kg or 108% of the actual-Dose X. Comparing the underdosed Dose X with the adequately prescribed Dose X, those underdosed had higher rates of ulcerative colitis (20% vs 11%, p<0.02), lower trough infliximab levels (2.6 vs 7.8 mg/L; p<0.0001) and lower albumin levels (37 vs 39 g/L; p<0.0001). There was no difference regarding gender, immunomodulator use, length of infliximab therapy or disease duration.

Conclusion Half of maintenance infliximab drug doses given at our institution were too low to achieve therapeutic infliximab blood levels. These patients would likely benefit from an increased dose or reduced dosing interval of infliximab. Our findings need to be confirmed prospectively.

 

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Artikel online veröffentlicht:
19. August 2022