Table 1.
Clinical response induction data for monoclonal antibodies for Crohn’s disease.
| Author/trial | Treatment groups/induction dose | Response rate | Response definition | Patient population | Comment | Ref. |
|---|---|---|---|---|---|---|
| Infliximab | ||||||
| Targan et al. | Placebo | 17% | CDAI decrease of 70 points at week 4 | Moderate-to-severe CD | This was the first study so patients were consequently naive to biologic therapy by definition and were sicker overall (hence very low placebo rate) | [12] |
| 5 mg/kg | 81% | |||||
| 10 mg/kg | 50% | |||||
| 20 mg/kg | 64% | |||||
| 65% overall | ||||||
| ACCENT I | Week 0: 5 mg/kg | 58% at 2 weeks | Decrease of CDAI 70 points from baseline and 25% reduction in total score at week 2 | Active CD with CDAI: >220 | By definition, only those who responded to 5 mg/kg could advance in this trial, which skews the overall data. However, this sets the stage for dose escalation in those who lose response | [15] |
| Week 2 and 6 and 8 weeks after: placebo (group 1) | ||||||
| 5 mg/kg (group 2) | ||||||
| 5 mg/kg for weeks 2 and 6, and 10 mg/kg for every 8 weeks (group 3) | ||||||
| Adalimumab | ||||||
| CLASSIC I | Week 0/2: | Remission as defined by CDAI <150 at week 4 | Moderate-to-severe CD naive to anti-TNFs | Remission rates were comparable to those achieved with infliximab | [26] | |
| Placebo | 12% | |||||
| 40/20 mg | 18% | |||||
| 80/40 mg | 24% | |||||
| 160/80 mg | 36% | |||||
| CHARM | Week 0: 80 mg | 91% of patients who received this dose met the week 4 end point | Decrease in CDAI >70 points from baseline at week 4 | Moderate-to-severe CD | Primary end point of trial was remission at week 26/54 | [29] |
| Week 4: 40 mg | ||||||
| GAIN | Week 0/2: | Response was CDAI 70-point decrease from baseline or CDAI >100 | Patients with persistent symptoms or intolerant to infliximab | Showed that patients could be safely and effectively switched to Humira® after losing response to infliximab | [32] | |
| Placebo | CDAI 70: 34% | |||||
| CDAI 100: 25% | ||||||
| 160/80 mg | CDAI 70: 52% | |||||
| CDAI 100: 38% | ||||||
| Certolizumab | ||||||
| PRECISE 1 | Week 0, 2 and 4 and then every 4 weeks | Decrease of CDAI of 100 points at week 6 | Moderate-to-severe CD, CRP >10 | High placebo rate obscured clinical effect | [36] | |
| Placebo | 27% | |||||
| 400 mg | 35% | |||||
| PRECISE 2 | Week 0, 2 and 4 | 64% | Decrease of CDAI of 100 points at week 6 | Moderate-to-severe CD | Study was designed for maintenance, not to evaluate induction | [39] |
| 400 mg | ||||||
| Natalizumab | ||||||
| Gordon et al. | One infusion | Remission as defined by change in mean CDAI at 2 weeks and remission (CDAI <150) | Mild-to-moderate CD | [46] | ||
| Placebo | 8% | |||||
| 3 mg/kg | 39% | |||||
| Ghosh et al. | Two infusion 4 weeks apart | Remission as defined by CDAI <150 at week 6 | Moderate-to-severe CD (CDAI 220–450) | There was a signal for efficacy at week 8 (preset primary end point) but this was not significant. Had a statistically significant benefit at other time points | [47] | |
| Placebo | 17% | |||||
| 3 mg/kg + placebo | 20% | |||||
| 3 mg/kg + 3 mg/kg | 29% | |||||
| 6 mg/kg + 6 mg/kg | 16% | |||||
| ENACT-1 | Week 0, 4 and 8 | Response at week 10 as defined by reduction in CDAI by 70 points from baseline and remission (CDAI <150) | Moderate-to-severe CD | Did not achieve primary end point but thought to be related to high placebo response and inclusion of patients with low CRP (no active inflammation) | [48] | |
| Placebo | Response: 49% | |||||
| Remission: 30% | ||||||
| 300 mg | Response: 56% | |||||
| Remission: 37% | ||||||
| ENCORE | Week 0, 4 and 8 | Response as defined by decrease in CDAI by 70 points from baseline at week 8 and sustained to week 12 | Moderate-to-severe CD with elevated CRP | Established that this agent was effective at maintaining remission | [49] | |
| Placebo | 32% | |||||
| 300 mg | 48% | |||||
CD: Crohn’s disease; CDAI: Crohn’s disease activity index; CRP: C-reactive protein; TNF: Tumor necrosis factor.