Table 2.

Published studies in adults on infliximab and antibodies to infliximab in Crohn’s disease and ulcerative colitis.

Reference	Study design	Population	Regimen	Follow up	ATI incidence	Impact of ATI
						Clinical response	Safety
Baert et al. [2003]	Prospective cohort	Refractory luminal and fistulizing CD (n = 125)	Episodic (luminal: 1 infusion; fistulizing: 3 infusions + on demand)	Median 36 months	Overall: 61% (37% ATI ≥8 μg/ml) +IS: 43% No IS:75% (p < 0.01 for +IS versus no IS)	Negative correlation between the concentration of ATI and the duration of response to IFX (p < 0.001): ATI concentration ≥ 8 μg/ml predictive of shorter response	Strong correlation between ATI concentration and infusion reactions: ATI ≥8 μg/ml predictive of infusion reactions (RR 2.4; 95% CI 1.65–3.66; p < 0.001)
Farrell et al. [2003]	Prospective, observational	Refractory luminal and fistulizing CD (n = 53)	Episodic (luminal: 1-2 infusions; fistulizing: 3 infusions + on demand)	Median 20 weeks	Overall: 36%: +IS: 24%: No IS: 63% (p = 0.007 for +IS versus no IS)	73% (11/15) of patients who lost initial response developed ATI; none of the continuous responders developed ATI	All 7 serious infusion reactions occurred in patients with ATI
Farrell et al. [2003]	Randomized, double blind, placebo controlled	Refractory luminal and fistulizing CD (n = 80)	Episodic	16 weeks	IFX alone: 42% IFX + IV corticosteroid: 26% (p = 0.06)	No direct data by ATI status	Trend to reduce infusion reactions by premedication with IV hydrocortisone; no direct data by ATI status
Hanauer et al. [2002]; ACCENT I	Randomized, double blind	Moderate to severe CD (n = 573)	Induction regimen followed by maintenance therapy	54 weeks	Overall: 14% Placebo: 28% IFX 5 mg/kg: 9% IFX 10 mg/kg: 6% +IS: lower rates	No direct data by ATI status	38% of ATI+ patients had an infusion reaction versus 24% of ATI– patients
Hanauer et al. [2004]; ACCENT I subanalysis	Randomized, double blind	Moderate to severe CD (n = 573)	Induction regimen followed by maintenance therapy	72 weeks	Overall: 16% Placebo: 30% IFX 5 mg/kg: 10% IFX 10 mg/kg: 7% +IS: lower rates	No association between ATI positivity and clinical response or remission	Patients who were ATI+ had ≥1 infusion reaction compared with patients who were ATI– (36% versus 24%; OR 1.8; 95% CI 1.1–3.1; p = 0.026)
Rutgeerts et al. [2005]; ACT 1	Randomized, double blind, placebo controlled	Moderate to severe UC (n = 229)	Induction regimen followed by maintenance therapy	54 weeks	Overall: 6.1% IFX 5 mg/kg: 7.8% IFX 10 mg/kg: 4.4%	No association between ATI positivity and clinical response Response:  ATI+: 21.4% (3/14)  ATI–: 8.3% (3/36) ATI inconclusive: 57.5% (103/179)	35.7% of ATI+ patients had infusion reactions compared with 9.8% of ATI– or ATI-inconclusive patients No ATI+ patient had a serious infusion reaction
Rutgeerts et al. [2005]; ACT 2	Randomized, double blind, placebo controlled	Moderate to severe UC (n = 188)	Induction regimen followed by maintenance	30 weeks	Overall: 6.4% IFX 5 mg/kg: 9.5% IFX 10 mg/kg: 3.2%	No association between ATI positivity and clinical response Response:  ATI+: 57.9% (11/19)  ATI–: 57.0% (45/79)  ATI inconclusive: 77.2% (71/92)	50% of ATI+ patients had infusion reactions compared with 9.7% of ATI– or ATI-inconclusive patients No ATI+ patient had a serious infusion reaction
Maser et al. [2006]	Prospective cohort	Refractory inflammatory and/or perianal fistulizing CD (n = 105)	Induction regimen followed by maintenance (n = 82) or episodic (n = 23) therapy	Median 88 weeks	Overall: 21% (77% ATI ≥8 μg/ml) Episodic: 39% Scheduled: 16% (p = 0.036 for episodic versus scheduled)	No association between ATI positivity and clinical remission	Incidence of infusion reactions higher in patients with ATI (50% versus 21%; OR 3.6; p = 0.018)
Vermeire et al. [2007]	Prospective, proof of concept	Refractory luminal and fistulizing CD (n = 174)	Episodic (luminal: 1 infusion; fistulizing: 3 infusions; + on demand)	Median 42 weeks	IFX alone: 73% +MTX: 44% +AZA: 48%	ATI associated with shorter duration of response in patients not taking IS (median 11.71 weeks) versus patients taking IS (median 13.8 weeks), but p = NS	Lower rates of infusion reactions with IS (16% versus 40%; p = 0.04)
Van Assche et al. [2008]	Randomized, open label	Moderate to severe CD (n = 80)	Maintenance therapy	2 years	Overall: 18% +AZA: 5.0% No AZA: 12.5%	No association between ATI positivity and IFX trough levels	NR
Colombel et al. [2010]; SONIC	Randomized, double blind	Moderate to severe CD; naive to immunomodulator and anti-TNF therapy(n = 508)	IFX alone or AZA alone or IFX + AZA combination therapy	50 weeks	IFX alone: 14.6% Combination: 0.9%	Clinical remission rates at week 26 and 50 were higher in ATI-inconclusive patients than ATI+ or ATI– patients	NR
Seow et al. [2010]	Prospective, cohort	Moderate to severe UC (n = 115)	Induction regimen followed by maintenance	54 weeks	Overall: 41%  33/44 ATI+ patients had a titer of >8 µg/ml 16/44 developed ATI with ≤3 infusions	Rates of clinical remission, endoscopic improvement, and colectomy similar between ATI+ and ATI– patients	59% of infusion reactions (n = 17) occurred in ATI+ patients
Afif et al. [2010]	Retrospective review	Patients with CD, UC, or indeterminate colitis who underwent ATI and IFX concentration measurement (n = 155)	–	–	35 (25%) patients were ATI +	Of the 177 total tests assessed, immunogenicity or IFX trough levels were found to affect treatment decisions in 73% of patients Complete or partial response was achieved in 92% of patients with detectable ATI levels who switched to another anti-TNF agent compared with 17% who were dose escalated (p < 0.004)	–

ACCENT I, A Crohn’s Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I; ACT 1 and 2, Acute Ulcerative Colitis Treatment 1 and 2; ATI, antibodies to infliximab; AZA, azathioprine; CD, Crohn’s disease; CI, confidence interval; IFX, infliximab; IS, immunosuppressant; MTX, methotrexate; NR, not reported; OR, odds ratio; SONIC, Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease; TNF, tumor necrosis factor; UC, ulcerative colitis.