Abstract
Aims
We determined adalimumab utilisation and associated drug costs in patients with ulcerative colitis (UC), focusing on patients requiring dose escalation.
Methods
The retrospective cohort study analysed the de-identified prescription data of the Arvato Health Analytics (Munich, Germany) database (2010–2015) in adult UC patients undergoing adalimumab therapy.
Results
A total of 154 patients were newly treated with adalimumab (average 39.6 years, 53% females), with a mean dose of 2.93 mg/day. Within 12 months, 69 patients (45%) received a dose increase of > 50% (doubled dose in 48 patients; 32%), with the escalation reported at 169.3 ± 99.3 days. A subsequent dose de-escalation to the standard dose occurred in 50 (32%) of patients that initially had a dose increase of > 50% (after 94.7 ± 49.6 days). Direct drug costs were 28,846 € in the overall study population, 24,934 € in patients on standard dose, 36,094 € in patients with dose increase, and 32,742 € in patients with increase and subsequent decrease.
Conclusion
Dose escalation occurred frequently, and in one third of patients the dose was at least doubled. Dose escalations were associated with substantial increases in direct drug costs. Dose escalation of adalimumab can severely affect both the health care system and the drug budget of the physician. It needs to be considered that other biologic medications may constitute a more cost-effective alternative.
Similar content being viewed by others
References
Ordas, I., Eckmann, L., Talamini, M., Baumgart, D.C., Sandborn, W.J.: Ulcerative colitis. Lancet 380(9853), 1606–1619 (2012)
Kornbluth, A., Sachar, D.B.: Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am. J. Gastroenterol. 105(3), 501–523 (2010)
Dignass, A., Van Assche, G., Lindsay, J.O., Lemann, M., Soderholm, J., Colombel, J.F., et al.: The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J. Crohns Colitis 4(1), 28–62 (2010)
Hindryckx, P., Baert, F., Hart, A., Magro, F., Armuzzi, A., Peyrin-Biroulet, L.: Clinical trials in ulcerative colitis: a historical perspective. J. Crohns Colitis 9(7), 580–588 (2015)
Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten (DGVS). Colitis ulcerosa: Diagnostik und Therapie (no. 021-009). Issued in 2009, currently under revision. http://www.awmf.org/leitlinien/detail/ll/021-009.html. Accessed 24 July 2017
Dignass, A., Preiss, J.C., Aust, D.E., Autschbach, F., Ballauff, A., Barretton, G., et al.: Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011. Z. Gastroenterol. 49(9), 1276–1341 (2011)
Harbord, M., Eliakim, R., Bettenworth, D., Karmiris, K., Katsanos, K., Kopylov, U., et al.: Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management. J. Crohns Colitis 11(7), 769–784 (2017)
Decision Resources Group (DRG).: Immune and inflammatory disorders. Ulcerative colitis. Analyzing and forecasting the commercial outlook for drugs on the market and in research and development. Report updated in September 2015. Decision Resources Burlington, MA, USA
European Medicines Agency (EMA).: Humira EMEA/H/C/000481-II/0156. Summary of product characteristics (SPC). http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000481/human_med_000822.jsp&mid=WC0b01ac058001d124. Accessed 3 Dec 2016
Armuzzi, A., Pugliese, D., Nardone, O.M., Guidi, L.: Management of difficult-to-treat patients with ulcerative colitis: focus on adalimumab. Drug Des. Dev. Ther. 7, 289–296 (2013)
Molodecky, N.A., Soon, I.S., Rabi, D.M., Ghali, W.A., Ferris, M., Chernoff, G., et al.: Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(1), 46–54 (2012). (quiz e30)
Wolf, D., D’Haens, G., Sandborn, W.J., Colombel, J.F., Van Assche, G., Robinson, A.M., et al.: Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment. Pharmacol. Ther. 40(5), 486–497 (2014)
Summary of product characteristics (SPC)/prescribing information adalimumab (Humira 40 mg). Manufacturer AbbVie, UK, June 2016. http://www.fachinfo.de. Accessed 3 Dec 2016
IMS Health.: Prescriptions and market share of biologics in gastroenterology. Internal data IMS Sell NI. (2017)
IMS Health.: Share of TNF α inhibitors in various gastrointestinal diseases in Germany. Unpublished report (2016)
Black, C.M., Yu, E., McCann, E., Kachroo, S.: Dose escalation and healthcare resource use among ulcerative colitis patients treated with adalimumab in English hospitals: an analysis of real-world data. PLoS ONE 11(2), e0149692 (2016)
Salomonsson, S., Soderberg, J., Alenadaf, K., Ljung, T.: Dose escalation among ulcerative colitis patients treated with adalimumab in Sweden. Value Health 18(7), A633 (2015)
Motheral, B., Brooks, J., Clark, M.A., Crown, W.H., Davey, P., Hutchins, D., et al.: A checklist for retrospective database studies—report of the ISPOR Task Force on Retrospective Databases. Value Health 6(2), 90–97 (2003)
Arbeitsgruppe Erhebung und Nutzung von Sekundärdaten der Deutschen Gesellschaft für Sozialmedizin und Prävention, Arbeitsgruppe Epidemiologische Methoden der Deutschen Gesellschaft für Epidemiologie, Deutsche Gesellschaft für Medizinische Informatik Biometrie und Epidemiologie, Deutsche Gesellschaft für Sozialmedizin und Prävention. Good practice of secondary data analysis, first revision. Gesundheitswesen 70(1), 54–60 (2008) (original in German)
Drösler, S., Hasford, J., Kurth, B.-M., Schaefer, M., Wasem, J., Wille, E.: Evaluationsbericht zum Jahresausgleich 2009 im Risikostrukturausgleich. https://www.bundesgesundheitsministerium.de/fileadmin/dateien/Publikationen/Gesundheit/Forschungsberichte/Evaluationsbericht_zum_Jahresausgleich.pdf. Accessed 6 Nov 2016
Swart, E., Bitzer, E.M., Gothe, H., Harling, M., Hoffmann, F., Horenkamp-Sonntag, D., et al.: [A consensus German reporting standard for secondary data analyses, Version 2 (STROSA-STandardisierte BerichtsROutine fur SekundardatenAnalysen)]. Gesundheitswesen 78(S01), e161 (2016)
Schwabe, U., Paffrath, D.: Arzneiverordnungs-Report 2016: Aktuelle Daten, Kosten, Trends und Kommentare. Kapitel 3 Neue Arzneimittel, Seite 57: Springer Berlin Heidelberg
R Development Core Team: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria (2017)
Armuzzi, A., Biancone, L., Daperno, M., Coli, A., Pugliese, D., Annese, V., et al.: Adalimumab in active ulcerative colitis: a “real-life” observational study. Dig. Liver Dis. 45(9), 738–743 (2013)
Afif, W., Leighton, J.A., Hanauer, S.B., Loftus Jr., E.V., Faubion, W.A., Pardi, D.S., et al.: Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab. Inflamm. Bowel Dis. 15(9), 1302–1307 (2009)
Gies, N., Kroeker, K.I., Wong, K., Fedorak, R.N.: Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort. Aliment. Pharmacol. Ther. 32(4), 522–528 (2010)
Oussalah, A., Laclotte, C., Chevaux, J.B., Bensenane, M., Babouri, A., Serre, A.A., et al.: Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience. Aliment. Pharmacol. Ther. 28(8), 966–972 (2008)
Baki, E., Zwickel, P., Zawierucha, A., Ehehalt, R., Gotthardt, D., Stremmel, W., et al.: Real-life outcome of anti-tumor necrosis factor alpha in the ambulatory treatment of ulcerative colitis. World J. Gastroenterol. 21(11), 3282–3290 (2015)
Sandborn, W.J., van Assche, G., Reinisch, W., Colombel, J.F., D’Haens, G., Wolf, D.C., et al.: Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 142(2), 257–265 (2012)
Colombel, J.F., Sandborn, W.J., Ghosh, S., Wolf, D.C., Panaccione, R., Feagan, B., et al.: Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2, and 3. Am. J. Gastroenterol. 109(11), 1771–1780 (2014)
Beschluss des Gemeinsamen Bundesausschusses (G-BA) über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII—Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V—Vedolizumab. 8 Jan 2015. BAnz AT 9 (2015)
Reinisch, W., Sandborn, W.J., Hommes, D.W., D’Haens, G., Hanauer, S., Schreiber, S., et al.: Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 60(6), 780–787 (2011)
Funding
This study was funded by MSD Sharp & Dohme GmbH, Haar, Germany.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pöllinger, B., Schmidt, W., Seiffert, A. et al. Costs of dose escalation among ulcerative colitis patients treated with adalimumab in Germany. Eur J Health Econ 20, 195–203 (2019). https://doi.org/10.1007/s10198-017-0953-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10198-017-0953-z