Superior Treatment Persistence With Ustekinumab in Crohn's Disease and Vedolizumab in Ulcerative Colitis Compared With Anti-TNF Biological Agents

Real-world Registry Data From the Persistence Australian National IBD Cohort (PANIC) Study

Yanna Ko; Sudarshan Paramsothy; Yunki Yau; Rupert W. Leong

Disclosures

Aliment Pharmacol Ther. 2021;54(3):292-301. 

In This Article

Abstract and Introduction

Abstract

Background: Medication persistence contributes real-world evidence about treatment effectiveness, tolerability and prescriber and patient acceptability.

Aims: To evaluate persistence of biological agents in Crohn's disease (CD) and ulcerative colitis (UC) and the effects of immunomodulator use and treatment lines.

Methods: Retrospective national population-based data on treatment persistence for adalimumab, infliximab vedolizumab and ustekinumab for CD and UC were analysed from the Australian Pharmaceutical Benefits Scheme using Kaplan-Meier analysis and Cox proportional hazards models.

Results: There were 2499 patients included with 8219 person-years of follow-up. In CD patients ustekinumab had increased persistence compared to anti-TNF agents (HR: 1.79, 95%CI: 1.32–2.38, P < 0.01). Twelve-month CD persistence rates were ustekinumab 80.0%, vedolizumab 73.5%, infliximab 68.1% and adalimumab 64.2% (P = 0.01). In moderate-severe UC vedolizumab had increased persistence compared to anti-TNF agents (HR: 1.67, 95% CI: 1.27–2.18 P < 0.001). Twelve-month UC persistence rates were vedolizumab 73.4%, infliximab 61.1% and adalimumab 45.5% (P < 0.001). Immunomodulator co-therapy did not significantly increase persistence in non-anti-TNF therapy (P > 0.05). Thiopurines increased persistence of anti-TNF agents in CD (P < 0.001) and UC (P = 0.03). Methotrexate co-therapy increased persistence of anti-TNF agents in CD (P = 0.001) only. First-line therapy was superior to non-first line in persistence (P < 0.001). In fistulising CD, the persistence of infliximab and adalimumab was not significantly different (P = 0.11).

Conclusion: Persistence was highest in ustekinumab in CD and vedolizumab in UC. Factors which increased the persistence of biological agents are first-line therapy, and immunomodulator co-therapy in anti-TNF agent use.

Introduction

The inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) cause episodic gastrointestinal tract inflammation that may result in cumulative intestinal damage and disability.[1,2] Biological agents are available to treat IBD patient's refractory to conventional treatment. They include anti-tumour necrosis factor (anti-TNF) agents infliximab, adalimumab, and golimumab and the newer non-anti-TNF biological agents vedolizumab, ustekinumab and tofacitinib.[3] As there has been only one head-to-head trial of biological therapies to date (that compared the efficacy of vedolizumab vs adalimumab in moderate-to-severe UC for up to 1 year[4]), choice of biological agents has been based more on comparisons to standard care plus placebo, theoretical advantages and disadvantages, drug availability, cost and experience. Less than one third of IBD patients meet trial inclusion criteria. Moreover, maintenance data of randomised controlled trials (RCTs), typically do not extend beyond 1 year.[5] Clinical trials also do not capture nuanced factors affecting a patients' and physicians' decisions to adhere to long-term biological therapy. As such, real-world data have increasingly been used to provide comparative data between available biological agents.

Persistence is the proportion of subjects continuing a medication over time,[6] and is a surrogate marker for patient and physician willingness to continue treatment, ongoing treatment efficacy, and absence of significant adverse effects, in the real-world setting.[7] Adverse effects impacting drug persistence include risk of infusion reactions, infections and malignancy. Drug immunogenicity is associated with secondary loss of response in over 50% of patients on anti-TNF agents[8] and also decreases medication persistence. Immunogenicity may be reduced with thiopurine co-therapy,[9] but whether methotrexate also reduces immunogenicity in IBD is unclear. Whether immunomodulator co-therapy improves persistence of the newer biological agents vedolizumab and ustekinumab is also unknown. When analysed at a population level where there is no hierarchical prescribing order, persistence allows for direct comparison between drugs in an unbiased manner.

Aims

The primary aim of this study was to analyse persistence of IBD biological agents in a large, population-based cohort where patients have universal access to government subsidised medications without mandated prescribing order. The secondary aim was to examine factors affecting treatment persistence such as combined co-therapy with thiopurine or methotrexate immunomodulator, IBD phenotype, patient age, sex and biological agent line of therapy.

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