OBJECTIVES

: Dose escalation (DE) of biologics is an important indicator of lacking therapeutic efficacy. So far, no study discussed different methodological approaches on how to identify biologic DE in claims data. The aim of this study was to develop a stepwise methodology, and to test this in inflammatory bowel disease (IBD) patients.

METHODS

: In a dataset comprising claims of several German sickness funds, patients with confirmed diagnosis of Crohn’s disease or ulcerative colitis starting biologics therapy between 01/07/2015-30/06/2016 and a follow-up of 12 months were included. DE was assessed in three steps: (1) The maintenance phase for each agent was defined according to the Summary of Product characteristics (SmPC). (2) DE was identified through two signals: First, a prescribed dosage (PD) of >150% (sensitivity: >125%) of the recommended maintenance dosage in the SmPC on at least two consecutive prescriptions or secondly, a PD >150% (sensitivity: >125%) compared to the patient-individual PD between the first and second prescription in the maintenance phase. (3) A patient was altogether defined as dose escalator if both “signals” indicated DE.

RESULTS

: We identified 1,248 patients starting Adalimumab (ADA; n=502), Golimumab (GOL; 77), Infliximab (IFX; 441) or Vedolizumab (VDZ; 228) therapy. Percentage of patients with a maintenance PD >150/>125% in comparison to the SmPC was 15.1/19.9% (ADA), 5.2/5.6% (GOL), 14.7/25.6% (IFX), and 19.7/27.2% (VDZ); in comparison to the first PD in the maintenance phase these were 7.4/13.5% (ADA), 9.1/13.0% (GOL), 8.6/15.6% (IFX), and 6.6/11.8% (VDZ). Altogether, 4.4-8.4% (ADA), 7.8-11.7% (GOL), 6.3-13.6% (IFX), and 5.7-8.8% (VDZ) of patients were characterized as dose escalators.

CONCLUSIONS

: Methodological assumptions influence reported DE rates substantially, especially the definition from a medical view (dose increase during therapy, independent from initial dose) compared to a technical view (higher dose compared to SmPC). Further data and expert discussion is needed to assure comparability in IBD and other indications.