Dose Escalation Patterns and Associated Costs of Advanced Therapies for Ulcerative Colitis in France and the United Kingdom: A Retrospective Database Analysis

Abstract

Background: Dose escalation to optimize advanced therapies is common in ulcerative colitis (UC) to avoid intra-class or inter-class drug switching and maintain clinical response and has impact on costs. Given the limited real-world data available, this study aims to understand real-world dose escalation UC advanced therapies patterns in France and United Kingdom [UK].

Methods: Retrospective study in adult patients with moderate-to-severe UC starting an advanced UC therapy (adalimumab [ADA], golimumab [GOL], infliximab [IFX], tofacitinib [TOF], ustekinumab [UST], or vedolizumab [VED]) with first prescription (and/or dispensation for France) between January 2017 and February 2022 (ie advanced UC therapy new users, by excluding patients who used any of these drugs in the previous 12 months to their index date). Proportions of patients with dose escalation/de-escalation (±20% versus Summary of Product Characteristics) after maintenance date were estimated using Kaplan-Meier (KM) survival analyses. Clinical response, healthcare resource utilization (HRU) and direct costs related to UC were also analyzed.

Results: Within 6 months after start of maintenance, rate of at least one dose escalation was 74.1%. Overall, 83.9-89% of patients had dose escalation within the 12-24 months, respectively, and 61.6% had clinical response [ranging from 56.3% (ADA) to 77.0% (IFX)]. Direct annual HRU costs related to UC ranged between 7426 (IFX) EUR and 22,265 (UST) in France, with mean 11,181 EUR in the dose-escalation group vs 8323 EUR in the de-escalation group (+11.5%). In the UK costs ranged between 5006 (ADA) EUR and 11,975 (UST).

Conclusion: Dose escalation of UC advanced therapies is a common strategy to avoid treatment-switching. Despite dose escalations and their cost to the system, a proportion of patients fail to achieve clinical response. This study highlights the need for more efficacious, durable treatments for moderate-to-severe UC patients, as the initiation of the advanced therapies did not reduce overall systemic/rectal corticosteroid burden.

Keywords: biologics; dose escalation; economic cost; healthcare resource use (HRU); ulcerative colitis.

Figure 1

Cohort Flow Diagram by Countries.

Figure 2

(A) Kaplan Meier (KM)-estimated percentages of patients with dose escalation (ie, received an average daily dose >20% higher than specified in the label) during the maintenance phase until 24 months of follow-up, by treatment cohort (As-Treated [AT] approach). (B) KM Curve for Time to First Dose Escalation by treatment cohort (AT approach).

Figure 3

Clinical response in escalated patient versus non escalated patients, by treatment cohort (As-Treated approach).

Figure 4

Mean yearly direct medical costs by patient. (A) France and (B) UK. Results for upadacitinib are not shown since there is only one patient, but they are included in the Total column. *Cost is averaged across all patients. Cost was calculated yearly average, using Lin’s method, weighted by KM probability of each month follow up. ‡ Cost were calculated in British pound (GBP) and converted to euros (€). Change considered: 1 GBP = 1,1629 euros (July 3, 2023).