Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia

Figures & data

Figure 1. Flowchart of study population. *Answers to questions regarding TDM of biologic agents were lacking.

Table 1. Demographic and clinical characteristics of study participants (n = 297).

Demographics (n)	Study participants n (%)
Country
Norway	118 (40)
Denmark	86 (29)
Sweden	50 (17)
Finland	33 (11)
Iceland	10 (3)
Grade
Gastroenterology specialist /trainee	252 (85)/45 (15)
Specialist experience (years)
<5/5–10/10–20/≥20	54 (21)/50 (20)/81 (32)/66 (27)
Trainee practice (years)
<3/≥3	18 (40)/27 (60)
Practice setting
University hospital	152 (51)
Non-university hospital	136 (46)
Private specialist practice	9 (3)
Hospital catchment area
<100.000/100.000-300.000/≥300.000	59 (20)/126 (43)/111 (38)
Size of IBD cohort^a
<500/500-1.000/≥1.000	87 (29)/54 (18)/116 (39)
Size of IBD cohort on biologic agents^b
<200/≥200	118 (40)/126 (43)
IBD patients, contacts/week^c
<10/≥10	98 (33)/198 (67)
IBD patients on biologic agents, contacts/week
<10/≥10	198 (67)/97 (33)

^aMissing data n = 38.

^bMissing data n = 50.

^cNumber of contacts with IBD patients reported by the physician per week.

Table 2. Use of reactive and proactive TDM across different biologic drugs.

	Reactive TDM n (%) (n = 231)		Proactive TDM n (%) (n = 161)
	Primary non-response	Secondary loss of response	Induction	Maintenance
Use of TDM n (%)	172 (74)	228 (99)	90 (56)	129 (80)
Biologic agent
Infliximab	168 (98)	220 (96)	85 (94)	125 (97)
Adalimumab	154 (90)	206 (90)	71 (79)	121 (94)
Golimumab	71 (41)	93 (41)	42 (47)	72 (56)
Vedolizumab	108 (63)	143 (63)	57 (63)	98 (76)
Ustekinumab	76 (44)	108 (47)	43 (48)	78 (60)

The physicians were able to check all the above options in the questionnaire.

Figure 2. The use of reactive versus proactive TDM of biologic agents among physicians in Scandinavia. Distribution of the current use of reactive and proactive TDM in clinical practice in Norway, Denmark, Sweden, Finland, and Iceland presented as frequencies (%). P-values are generated from multivariate logistic regression models, adjusted for country, employment at university hospital, size of hospital catchment area, seniority, and number of IBD contacts per week.

Table 3. Factors associated with use of proactive TDM of biologic agents (n = 297).

Variable (n)	Univariate OR [95%CI]	p Value	Multivariate OR [95%CI]	p Value
Country
Norway	1		1
Denmark	0.03 [0.01,0.06]	<.001	0.02 [0.01,0.04]	<.001
Sweden	0.29 [0.14,0.60]	.001	0.22 [0.09,0.52]	.001
Finland	0.85 [0.33,2.21]	.74	0.54 [0.19,1.50]	.24
Iceland	0.06 [0.01,0.29]	.001	0.07 [0.01,0.40]	.003
Practice setting
University hospital	1		1
Community hospital	2.14 [1.33,3.43]	.002	0.88 [0.42,1.83]	.73
Private practice	1.50 [0.39,5.82]	.56	0.60 [0.13,2.84]	.52
Grade
Trainee	1		1
Specialist	1.43 [0.76,2.70]	.28	1.43 [0.61,3.34]	.41
Hospital catchment area
<300.000	1		1
>300.000	0.61 [0.38,0.99]	.044	1.19 [0.54,2.61]	.67
IBD contacts/week^a
<10	1		1
>10	1.30 [0.80,2.12]	.29	2.71 [1.34,5.48]	.005

Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Univariate and multivariate p-values ≤0.05 in bold. Variables tested but did not come out significant in univariate or multivariate analysis included specialist experience in years, trainee practice training in years, size of IBD cohort, and number of contacts with IBD patients on biological therapies per week.

^aNumber of contacts with IBD patients reported by the physician per week.

Figure 3. Barriers hindering the implementation of TDM of biological therapy in clinical practice in Scandinavia. Barriers and reasons for not using TDM of biologic agents among physicians in Scandinavia presented as frequencies (%)*. *Missing data: n = 52.

Table

	Induction phase	Maintenance phase
Infliximab	w2: 20–25 µg/mL w6: 10–15 µg/mL w14: 7–10 µg/mL	5 µg/mL
Adalimumab	w4: 12 µg/mL	8 µg/mL
Golimumab	w6: 2.5–3.8 µg/mL	1.4 µg/mL
Vedolizumab*	w6: 20–30 µg/mL w14: 15–20 µg/mL	10–15 µg/mL
Ustekinumab*	w8: 4–7 µg/mL	1–2 µg/mL

Therapeutic thresholds are affected by: Outcome measure (higher at more profound remission: clinical-biochemical-endoscopic-histological), disease phenotype (higher for fistulizing and small bowel Crohn’s disease than luminal colonic disease), and disease activity at time of testing (higher at more severe disease activity) [3,12,22,25,38,39].

*Limited data.

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Data availability statement

The data underlying this article are available in the article and in its online supplementary material.