TABLE 1.

Overview of Trials Investigating TDM of TNF Antagonists for CD

Study	Number of Patients	Study Design	Intervention	Primary Endpoint	Results
Efficacy studies
Vande Casteele, Ferrante, et al (TAXIT trial)3	N = 263 patients with CD or UC	1-y prospective randomized controlled trial	IFX	Clinical and biochemical remission at 1 y after optimization phase	No differences in clinical, biological, and endoscopic remission between IFX TC-based dosing and clinically based dosing arms; however, TC-based dosing was associated with fewer flares requiring rescue therapy and more efficient use of drug.
D’Haens et al (TAILORIX trial)49	N = 122 patients with CD randomized to 3 maintenance regimens: (1) dose intensification based on clinical symptoms, biomarker analysis, and serum TC IFX; (2) dose intensification of IFX to 5-10 mg/kg based on the same criteria; (3) IFX dose intensification to 10 mg/kg based on clinical symptoms alone	Prospective randomized double-blind controlled trial	IFX	Sustained, steroid-free clinical remission from weeks 22-54 and absence of ulceration at 1 y based on endoscopy	Proactive IFX TC-based dose intensification was not superior to clinically based dose intensification.
Paul, Del Tedesco, et al45	N = 52 patients with CD or UC with secondary failure to IFX	Prospective 8-wk cohort study	IFX	n/a	An increase in IFX TC after dose optimization was associated with mucosal healing in patients with CD and with UC (P = 0.001).
Assa et al63	N = 78 pediatric patients with CD naïve to treatment with TNF antagonists	Nonblinded randomized controlled trial	ADA	Sustained corticosteroid-free clinical remission at all visits (wks 8-72)	Proactive TDM of ADA TCs resulted in significantly higher rates of corticosteroid-free clinical remission than did reactive TDM.
Chiu et al55 CLASSIC subanalysis	N = 275 patients with CD receiving ADA as induction therapy in CLASSIC I and II studies	Prospective study	ADA	n/a	A positive correlation between serum ADA and remission was identified at several time points up to week 56.
Karmiris et al60	N = 168 patients with CD after failure of IFX therapy	Prospective observational study	ADA	n/a	ADA TCs were lower in patients who discontinued; patients with ADA ADAbs had lower median ADA TC throughout entire follow-up period (P < 0.0001)
Bodini, Giannini, Savarino, et al54	N = 23 patients with CD	Prospective 72-week study	ADA	n/a	ADA TCs were significantly higher (11.9 µg/mL) in patients with remission vs mild and moderate/severe disease (5.5 µg/mL; P = 0.0002).
Ward et al71	N = 19 patients with CD on maintenance ADA regimen had ADA concentrations measured repeatedly to predefined schedule	Prospective observational study	ADA	n/a	ADA concentrations ≥4.9 µg/mL obtained during the first 9 days predicted therapeutic ADA TCs with reasonable confidence.
Vande Casteele, Feagan, Vermeire, et al70	N = 2157 patients with CD	CZP simulation study based on data from 9 clinical trials	CZP	n/a	CZP concentrations of 36 µg/mL and 15 µg/mL at weeks 6 and 12 were associated with attaining a combined efficacy outcome of CDAI ≤150 and FCP ≤250 µg/g at week 26.
Cost-effectiveness studies
Steenholdt et al46, 47	N = 69 patients with secondary IFX failure were randomized to conventional dose intensification (5 mg/kg every 4 weeks) or interventions based on serum IFX and IFX ADAbs using an algorithm	Randomized controlled single-blind study	IFX	Accumulated mean cost per patient for CD at week 12 in the algorithm group vs the group receiving conventional dose intensification	Algorithm-based treatment achieved similar clinical, biological, and quality of life outcomes to conventional dose intensification but at significantly lower costs; this cost reduction was maintained for up to 1 year.

ADA indicates adalimumab; CDAI, Crohn’s Disease Activity Index; CZP, certolizumab pegol; IFX, infliximab; n/a, not available; TC, trough concentration.