70
activity in the IFX-treated group (80% AZA vs. 18% IFX). There were no signifi-
cant differences in clinical recurrence after 12 months.
Adalimumab (ADA) has similarly been studied for prevention of POR. First
reported by Savarino et al. in 2012 when treating six CD patients post- ileocecectomy,
ADA induction and maintenance (160/80/40 mg every 2 weeks) resulted in com-
plete clinical, radiographic, and endoscopic remission for 3 years [ 53 ]. Similarly, in
a prospective, 2-year, pilot study, Papamichael et al. followed 23 high-risk CD
patients after resection. Out of eight patients started on prophylaxis ADA (induction
followed by maintenance dosing) at day 14 post-resection, only 1/8 (12.5%) patient
had endoscopic recurrence at 6 months and 2/8 (25%) at 24 months [ 54 ]. The
remaining 15 patients demonstrated endoscopic POR at 6 months postoperative but
were intolerant to IFX and AZA. After 24 months of treatment with ADA, 9/15
(60%) achieved complete mucosal healing. These studies were limited by lack of
placebo arm. In a randomized controlled trial of ADA (160/80/40 mg every 2 weeks)
compared to AZA (2 mg/kg/day) or mesalamine (3 g/day) in prevention of POR,
Savarino et al. demonstrated significantly lower endoscopic recurrence rates in
patients treated with ADA compared to AZA (6.3% ADA vs. 64.7% AZA, OR
0.036, 95% CI 0.004–0.347) or mesalamine (83.3%, OR 0.013, 95% CI 0.001–0.14)
[ 55 ]. Similarly, ADA-treated patients had significantly lower rates of clinical recur-
rence (12.5% ADA vs. 64.7%, OR 0.078, 95% CI 0.013–0.464) and mesalamine
(50%, OR 0.143, 95% CI 0.025–0.819). Thus, similar to infliximab, adalimumab
appears to be superior to both thiopurines and 5-ASA agents in prevention of
POR. Recurrence rates utilizing various medications using data from randomized,
controlled trials are demonstrated in Table 5.4.
Using a Bayesian network meta-analysis strategy of direct and indirect compari-
sons, Singh et al. were able to compare treatment effects of multiple pharmacologic
interventions in preventing POR by combining data from 21 trials comprising 2006
postoperative CD patients with seven different treatment strategies [ 45 ]. Compared
to placebo for prevention of clinical recurrence (CDAI > 150 or clinical relapse as
defined by individual study investigators), mesalamine (RR 0.60, 95% CI 0.37–
0.88), antibiotics (RR 0.26, 95% CI 0.08–0.61), immunomodulator monotherapy
(RR 0.36, 95% CI 0.17–0.63), immunomodulator with antibiotics (RR 0.11, 95%
CI 0.02–0.51), and anti-TNF monotherapy (RR 0.04, 95% CI 0.00–0.14) were all
Table 5.4 One year clinical and endoscopic Crohn’s disease recurrence rates reported in
randomized controlled trials (Adapted from Regueiro [ 61 ])
Clinical recurrence (%) Endoscopic recurrence (%)
Placebo 25–77 53–79
5-Aminosalicylates 24–58 63–66
Budesonide 19–32 52–57
Nitroimidazole 7–8 52–54
Azathioprine/6-mercaptopurine 34–50 42–44
Antitumor necrosis factora 0–13 6–22
aIncludes infliximab and adalimumab
B.H. Click and M. Regueiro