Dose escalation of advanced therapies for Crohn's disease in Germany: a database analysis of German health insurance fund claims

Introduction: Dose escalation is a common strategy to address inadequate or lost response in patients (pts) with Crohn’s disease (CD); dose escalations or alternative dosing regimens are permitted in certain cases by the Summary of Product Characteristics (SmPC) of various biologic treatments. Given lack of recent data, we aimed to evaluate real-world data in pts with moderately to severely active CD in Germany to identify and characterize real-world dosing and escalation patterns for advanced biologic therapies.

Methods: We retrospectively analyzed data from the WIG2 benchmark database (anonymized healthcare claims). Adults (≥18 years) with moderately to severely active CD in Germany who started a new biologic therapy from 2020–2021 were included. Pts were required to have≥1 prescription for a CD-indicated biologic index drug (adalimumab, infliximab, ustekinumab, or vedolizumab) in the same quarter as≥1 CD diagnostic code, without a diagnostic code for ulcerative colitis. Analyses were conducted in the total group and stratified by biologic-naïve and -experienced pts. Dose escalations were defined as a>30% increase of the prescribed daily dose (PDD) compared with the minimum SmPC-recommended defined daily dose (DDD).

Results: In total, 816 German pts with CD from the WIG2 database who received≥1 advanced index therapy were included in this analysis. Baseline characteristics indicated demographic variations among pts receiving different index therapies, as well as between biologic-naïve and biologic-experienced pts ([Table 1]). Mean doses of index biologic therapies during the first 365 treatment days ([Table 2]) predominantly exceeded the SmPC-recommended minimum maintenance dose, especially in biologic-experienced pts. Within 12 months of maintenance dose initiation, pts having≥1 dose escalation ranged from 50% of pts treated with adalimumab to 86% treated with ustekinumab; dose escalation was generally more frequent in biologic-experienced pts. Mean time to dose escalation ranged from 95.3 days with ustekinumab to 123.2 days with vedolizumab, while the mean duration of dose escalation ranged from 54.9 days with vedolizumab to 131.4 days with ustekinumab ([Table 3]).

Table 1 Baseline characteristics

Index drug	Group	N	Mean age, years (SD)	Male sex, n (%)
Adalimumab	Total	328	40.1 (14.3)	143 (43.6)
	Biologic-naïve	260	40.4 (14.8)	110 (42.3)
	Biologic-experienced	68	38.9 (12.6)	33 (48.5)
Infliximab	Total	220	37.7(13.5)	104 (47.3)
	Biologic-naïve	136	38.8 (14.8)	75 (55.2)
	Biologic-experienced	84	35.9 (11.0)	29 (34.5)
Ustekinumab	Total	237	40.7 (14.9)	103 (43.5)
	Biologic-naïve	63	44.6 (16.0)	28 (44.4)
	Biologic-experienced	174	39.3 (14.2)	75 (43.1)
Vedolizumab	Total	177	41.9 (15.5)	81 (45.8)
	Biologic-naïve	56	44.1 (18.2)	21 (37.5)
	Biologic-experienced	121	40.9 (14.0)	60 (49.6)

SD, standard deviation.

Table 2 Prescribed maintenance dose of index advanced biologic therapies.

Index drug	Administration route	Group	Na	Mean PDD,b mg/day (SD)	Percent of minimum DDD,b mean (SD)
Adalimumab	s.c.	Total	254	3.11 (0.98)	108.8 (34.2)
		Biologic-naïve	198	3.02 (0.83)	105.8 (28.9)
		Biologic-experienced	56	3.42 (1.36)	119.5 (47.5)
Infliximab	i.v.	Total	129	8.78 (3.34)	129.4 (48.1)
		Biologic-naïve	78	8.77 (3.56)	127.0 (46.9)
		Biologic-experienced	51	8.81 (3.00)	133.0 (50.1)
	s.c.	Total	39	9.29 (3.13)	108.2 (36.5)
		Biologic-naïve	23	8.87 (1.19)	103.3 (13.9)
		Biologic-experienced	16	9.89 (4.70)	115.3 (54.8)
Ustekinumab	s.c.	Total	194	1.45 (0.37)	136.3 (35.2)
		Biologic-naïve	51	1.37 (0.27)	129.3 (25.6)
		Biologic-experienced	143	1.47 (0.40)	138.8 (37.9)
Vedolizumab	i.v.	Total	74	6.63 (2.76)	124.1 (51.6)
		Biologic-naïve	23	5.74 (1.31)	107.5 (24.5)
		Biologic-experienced	51	7.02 (3.14)	131.5 (58.7)
	s.c.	Total	63	7.48 (1.48)	96.9 (19.2)
		Biologic-naïve	18	6.75 (1.40)	87.4 (18.1)
		Biologic-experienced	45	7.77 (1.43)	100.7 (18.5)

^aPatients with at least two application-specific prescriptions of respective index drug in maintenance phase. ^bDDD and PDD are based on total prescribed dosage within the first 365 treatment days: Percentage values represent the PDD compared with the minimum recommended daily dose according to the SmPC. Values>100% indicate higher than minimum recommended dosing DDD, defined daily dose; i.v., intravenous; PDD, prescribed daily dose; s.c., subcutaneous; SD, standard deviation

Table 3 Dose escalationsa, time-to dose escalation, and duration of escalated advanced biologic therapies.

Index drug	Group	N	Patients with dose escalation, n (%)	Mean time to dose escalation,b days (SD)	Mean duration of dose escalation,b days (SD)
Adalimumab	Total	254	127 (50.0)	120.0 (113.2)	75.4 (74.7)
	Biologic-naïve	198	95 (48.0)	114.0 (110.6)	69.3 (67.0)
	Biologic-experienced	56	32 (57.1)	139.3 (120.5)	95.0 (93.7)
Infliximab	Total	157	108 (68.8)	113.5 (115.4)	82.8 (84.7)
	Biologic-naïve	97	62 (63.9)	121.2 (118.1)	87.5 (88.1)
	Biologic-experienced	60	46 (76.7)	102.6 (111.6)	76.2 (79.7)
Ustekinumab	Total	194	167 (86.1)	95.3 (115.4)	131.4 (101.6)
	Biologic-naïve	51	44 (86.3)	102.2 (119.2)	139.9 (109.0)
	Biologic-experienced	143	123 (86.0)	93.0 (114.3)	128.6 (99.1)
Vedolizumab	Total	127	73 (57.5)	123.2 (118.5)	54.9 (67.7)
	Bio-naïve	38	18 (47.4)	129.6 (126.7)	59.1 (95.8)
	Bio-experienced	89	55 (61.8)	121.4 (116.8)	53.6 (58.0)

^aDefined as>30% over minimal maintenance defined daily dose (based on the dosage between two prescriptions). ^bOnly patients who escalated dose were included. SD, standard deviation.

Conclusion: Our analysis of dosing patterns showed that maintenance dosing frequently exceeded the SmPC-recommended minimum across the analyzed advanced biologic therapies. Further, dose escalations were common during maintenance therapy.

 

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Artikel online veröffentlicht:
04. September 2025