Maarten Cozijnsen

120 Table 1. Continued Type Year Authors Patients N Treatment Duration Post-hoc analysis of 4 IFX RCTs* 2009 Lichtenstein et al (25) Adult CD, active disease (ACCENT I) or draining fistulas (ACCENT II) 1383 [1] IFX+IM [2] IFX 54 wks Post-hoc analysis of RCT* 2007 Colombel et al (CHARM) (37) Adult CD, moderate- to-severe disease 854 [1] ADA+IM [2] ADA 56 wks N=number; RCT=randomized clinical trial; CD=Crohn’s disease; IFX=infliximab; IM=immunomodulator (AZA or 6-mercaptopurine or MTX); MTX=methotrexate; PCB=placebo; AZA=azathioprine; ADA=adalimumab; CZP= certolizumab; wk=week; SES-CD=Simplified endoscopic score for CD; CFCR=Corticosteroid-free clinical remission; Overall, two RCTs have demonstrated that IFX combined with AZA, but not with MTX, increases remission rates in patients with active disease vs. IFX monotherapy.(11, 13) However, this modest treatment difference was achieved using a fixed IFX dosing schedule, i.e. precisely 5 mg/kg every 8 weeks. Individualization of therapy, with treatment targeted to adequate serum drug concentration, may nullify this efficacy difference. Secondly, although combination therapy did not improve remission maintenance rates nor failure rates in two RCTs, it did increase IFX trough levels and/or lowered the occurrence of ATIs in these trials. (13, 14) Results of post-hoc analyses of adult anti-TNF RCTs are conflicting. Lichtenstein et al (25) found similar remission rates in combination and monotherapy treated CD patients included in ACCENT 1 and 2 (321 received IFX, of whom 84 used concomitant IMs). However, concomitant IMs did reduce the occurrence of ATIs in ACCENT 2 (ACCENT I: 5/90 (6%) vs. 24/245 (10%), P≈0.2; ACCENT II: 1/42 (2%) vs. 15/83 (18%), P≈0.01), but median IFX concentrations did not differ. Kopylov et al (26), in a post-hoc analysis of ADA RCTs, found lower remission induction rates in mono vs. combination therapy treated patients (300/976 (31%) vs 365/1008 (36%), OR 0.78 (0.64-0.96)), but remission rates at 12 months were similar (152/337 (45%) vs 197/496 (40%), OR 1.08 (0.78-1.48)). Jones et al (27), in a post-hoc analysis of 11 anti-TNF RCTs, found higher remission rates at 6 months using combination therapy with IFX vs. monotherapy (OR 1.79 (1.06-3.01)), but not combination therapy with ADA (OR 0.88 (0.58-1.35)) or certolizumab (OR 0.93 (0.65-1.34)).