Drug utilization of biologic therapy in Crohn’s disease and ulcerative colitis: a population-based Danish cohort study 2015–2020

Abstract

Objective

The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015–2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression.

Results

Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.

When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29–0.89]), and for CD patients, although not significantly (0.58 [0.32–1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics.

Conclusion

More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.

Key summary

• Several biologic therapies are available in the treatment of ulcerative colitis and Crohn’s disease.

• Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.

• Drug utilization studies comparing biologic therapies head-to-head are sparse.

• In Denmark, during 2015–2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.

• One in four patients experienced more than one biologic during the study period.

• The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.

• Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

Keywords:

• Inflammatory bowel disease
• Crohn’s disease
• ulcerative colitis
• biological therapy
• treatment pattern
• drug utilization

Acknowledgments

We thank Mikkel Zöllner Ankarfeldt, Espen Jimenez Solem, Kristine Allin, and Kari Stougaard Jacobsen for invaluable input to the study design. The authors would further like to thank Kasper Vadstrup and Karen Jytte Summer former employees of Janssen Cilag A/S, for valuable input during the study progression.

Ethical approval

Ethical permission is not required for anonymized register studies according to Danish law. This study was approved by the Danish Data Protection Agency (ref. no. P-2020-39). The study was registered with ENCePP (EUPAS34845).

Author contributions

KJ and CB contributed equally to this work, share first authorship, and take responsibility for the integrity of the work as a whole, from inception to published article. KJ, CB, JP, CW designed the study. KJ, CB analyzed the data. JP supervised the statistical analyses. All authors contributed to the final version of the manuscript. All authors approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s). CW is employee of Janssen Cilag. The sponsor and its employee had no access to the data at any time or any role in the data management and data analysis of the study.

Data availability statement

Data analyzed for the present study is in the domain of Statistics Denmark (www.dst.dk) and cannot be transferred to third party. Access to data can be applied for through Statistics Denmark and the Danish Health Data Authority, respectively.

Additional information

Funding

This work was supported by Janssen Cilag A/S Denmark as a company sponsored study. JB reports personal fees from AbbVie, personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants from Bristol Myers Squibb, grants from Novo Nordisk, and personal fees from Pharmacosmos. CB, KJ, JP are employees of Phase4CPH.