Real-world biologic treatment and associated cost in patients with inflammatory bowel disease^[*]

Abstract

Objectives This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics’ dosage, health care resource use, and treatment-associated cost.

Methods In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohnʼs disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months.

Results In the database, 1248 out of 57 296 IBD patients started a biologic treatment of interest (1020 anti-TNF-α, 228 VDZ), and 837 patients were bio-naïve (773 anti-TNF-α, 64 VDZ). The mean age of bio-naïve/bio-experienced anti-TNF-α patients was 39.2/38.1 years (54.9 %/56.7 % female) and 42.6/37.8 years for VDZ patients (56.3 %/54.9 % female). The proportion of patients receiving a maintenance dosage > 150 % compared to SmPC was 15.1 % for Adalimumab, 5.2–39.0 % for Golimumab, 14.7–34.5 % for Infliximab, and 19.7 % for VDZ patients. During the maintenance phase, up to 58.8 % of patients received at least 1 prescription of any CS, and 41.7 %/47.1 % (anti-TNF-α/VDZ) were treated in a hospital due to IBD. The mean IBD-related direct health care cost per patient year was € 30 246 (anti-TNF-α)/ € 28 227 (VDZ) for bio-naïve patients (p = 0.288) and € 34 136 (anti-TNF-α)/ € 32 112 (VDZ) for bio-experienced patients (p = 0.011).

Conclusions A substantial percentage of patients receive a high biologic dosage in the maintenance phase. Despite biologic therapy, 30–40 % receive a CS therapy and/or experience at least 1 IBD-associated hospitalization within a year, possibly indicating a remaining disease activity.

Zusammenfassung

Fragestellung Ziel der Studie war die Beschreibung der Biologikatherapie von Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) in Deutschland.

Methode Diese retrospektive Krankenkassendatenstudie adressierte erwachsene Patienten mit CED (Morbus Crohn (MC) oder Colitis ulcerosa (UC)), die eine neue Therapie mit anti-TNFα oder Vedolizumab (VDZ) starteten. Die Beobachtungszeit von 12 Monaten begann mit der ersten Verordnung der neuen Therapie.

Ergebnisse 1248 von insgesamt 57 296 CED Patienten starteten eine neue Biologikatherapie (1020 anti-TNFα; 228 VDZ), 837 waren bio-naiv (773 anti-TNFα/64 VDZ). Das mittlere Alter der bio-naiven/bio-erfahrenen anti-TNFα Patienten betrug 39,2/38,1 Jahre (54,9 %/56,7 % Frauen), das der VDZ-Patienten 42,6/37,8 Jahre (56,3 %/54,9 % Frauen). Im Vergleich zu Empfehlungen aus der Fachinformation haben 15,1 % der Patienten mit Adalimumab, 5,2–39,0 % derjenigen mit Golimumab, 14,7–34,5 % derjenigen mit Infliximab und 19,7 % der VDZ-Patienten eine Erhaltungsdosis von > 150 % erhalten. Während der Erhaltungsphase haben 58,8 % Kortikosteroide erhalten, 41,7 %/27,1 % (anti-TNFα/VDZ) wurden aufgrund der CED stationär behandelt. Die CED-bezogenen direkten Kosten pro Patientenjahr lagen im Durchschnitt bei 30 246 € (anti-TNFα) bzw. 28 227 € (VDZ) für bio-naive (p = 0,288) und 34 136 € (anti-TNFα) bzw. 32 112 € (VDZ) für bio-erfahrene Patienten (p = 0,011).

Schlussfolgerungen Während der Erhaltungsphase erhält ein erheblicher Anteil der CED-Patienten eine hohe Biologikadosis. Dennoch haben innerhalb eines Jahres 30–40 % der Patienten Kortikosteroide erhalten und/oder eine CED-bezogene Hospitalisierung erlebt, was auf eine bestehende Krankheitsaktivität hinweisen könnte.

Key words

inflammatory bowel disease (IBD) - biologic treatment - ulcerative colitis - Crohnʼs disease - hospitalization - maintenance therapy

Schlüsselwörter

Chronisch-entzündliche Darmerkrankungen (CED) - Biologikatherapie - Colitis ulcerosa (UC) - Morbus Crohn (MC) - Hospitalisierung - Erhaltungstherapie

^* Author contributions: Conception and design of the study: A. B., A. G., T. W., B. A. R., Acquisition of data: A. F., B. D. Analysis and interpretation of data: A. B., A. G., T. W., B. A. R., H. D. O., B. B. Drafting the article: A. B., A. G., T. W., B. A. R., B. B. Critical review of the article: F. G., B. A. R., B. B., H. D. O., A. F., B. D. Finalizing the article: A. B., F. G., T. W., B. A. R., B. B. All authors have made substantial contributions to the study and writing of the article and have given their final approval of the version to be submitted.

• References

• 1 Bokemeyer B. CED-Behandlung in Deutschland: Betrachtungen zur sinnvollen Vernetzung. Der Gastroenterologe 2007; 2: 447-455
• 2 Loftus CG, Loftus EV, Harmsen WS. et al. Update on the incidence and prevalence of Crohnʼs disease and ulcerative colitis in Olmsted County, Minnesota, 1940–2000. Inflamm Bowel Dis 2007; 13: 254-261
• 3 Burisch J, Weimers P, Pedersen N. et al. Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study. J Crohns Colitis 2014; 8: 1030-1042
• 4 Dignass A, Preiß JC, Aust DE. et al. Aktualisierte Leitlinie zur Diagnostik und Therapie der Colitis ulcerosa 2011: Ergebnisse einer Evidenzbasierten Konsensuskonferenz. 2011
• 5 Preiß JC, Bokemeyer B, Buhr H. et al. Updated German Clinical Practice Guideline on “Diagnosis and Treatment of Crohn’s Disease”: AWMF-Registriernummer: 021-004 2014.
• 6 Gomollón F, Dignass A, Annese V. et al. 3rd European evidence-based consensus on the diagnosis and management of Crohnʼs disease 2016: part 1: diagnosis and medical management. J Crohns Colitis 2017; 11: 3-25
• 7 Harbord M, Eliakim R, Bettenworth D. et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis 2017; 11: 769-784
• 8 Entyvio: Summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/entyvio-epar-product-information_en.pdf
• 9 Humira: Summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/humira-epar-product-information_en.pdf
• 10 Remicade: Summary of product characteristics. Available at: https://www.ema.europa.eu/documents/product-information/remicade-epar-product-information_en.pdf
• 11 Simponi: Summary of product characteristics. Available at: https://ec.europa.eu/health/documents/community-register/2018/20180702141555/anx_141555_en.pdf
• 12 WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2017. Oslo: 2016
• 13 Anatomisch-therapeutisch-chemische Klassifikation mit Tagesdosen: Amtliche Fassung des ATC-Index mit DDD-Angaben für Deutschland im Jahre 2017. 2017
• 14 Blotière P, Rudant J, Barré A. et al. Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France (2011–2013). Dig Liver Dis 2016; 48: 620-625
• 15 Bähler C, Vavricka SR, Schoepfer AM. et al. Trends in prevalence, mortality, health care utilization and health care costs of Swiss IBD patients: a claims data based study of the years 2010, 2012 and 2014. BMC Gastroenterol 2017; 17: 138
• 16 van Deen WK, van Oijen MGH, Myers KD. et al. A nationwide 2010–2012 analysis of U.S. health care utilization in inflammatory bowel diseases. Inflamm Bowel Dis 2014; 20: 1747-1753
• 17 Stallmach A, Dennler U, Marschall U. et al. Patient-relevant endpoints in inflammatory bowel diseases--have changes occurred in Germany over the past twelve years?. J Crohns Colitis 2015; 9: 390-397
• 18 Bokemeyer B, Hardt J, Huppe D. et al. Clinical status, psychosocial impairments, medical treatment and health care costs for patients with inflammatory bowel disease (IBD) in Germany: an online IBD registry. J Crohns Colitis 2013; 7: 355-368
• 19 Gonczi L, Kurti Z, Rutka M. et al. Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases. BMC Gastroenterol 2017; 17: 97
• 20 Stark R, König H, Leidl R. Costs of inflammatory bowel disease in Germany. Pharmacoeconomics 2006; 24: 797-814
• 21 Prenzler A, Yen L, Mittendorf T. et al. Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine. BMC Health Serv Res 2011; 11: 157
• 22 Hoffmann F. Review on use of German health insurance medication claims data for epidemiological research. Pharmacoepidemiol Drug Saf 2009; 18: 349-356
• 23 Crystal S, Akincigil A, Bilder S. et al. Studying prescription drug use and outcomes with medicaid claims data: strengths, limitations, and strategies. Med Care 2007; 45: S58-S65