Maintenance infliximab infusions forever?

Abstract

The authors undertook a randomized controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn’s disease defined as having a Crohn’s Disease Activity Index ≥220. Initially, 573 patients were given a single dose of infliximab. The 335 patients (58%) who responded (Crohn’s Disease Activity Index decrease of >70 points) to this treatment at 2 wk were then randomized to receive repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (group I), repeat infusions of 5 mg/kg of infliximab (group II), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (group III). The prespecified coprimary endpoints were the proportion of patients who responded at wk 2 and were in remission (Crohn’s Disease Activity Index <150) at wk 30 and the time to loss of response up to wk 54 in patients who responded. The authors found that at wk 30, patients in groups II and III combined were more likely to sustain clinical remission than patients in group I (OR = 2.7, 95% CI = 1.6–4.6). At 30 wk, the remission rates for each group were: 23 of 110 (21%) in group I patients, 44 of 113 (39%) in group II ( p = 0.003), and 50 of 112 (45%) in group III ( p = 0.0002). The median time to loss of response was 38 and >54 wk for groups II and III, compared with 19 wk for group I ( p = 0.002 and p = 0.0002, respectively). At wk 54, patients in group II and III were significantly more likely to have discontinued steroids and remained in remission (OR = 4.2, 95% CI = 1.5–11.5), compared with those patients in group I. For patients in whom antibodies to infliximab could be measured, they were found in 28%, 9%, and 6% in groups I, II and III, respectively. There was a trend toward a lower incidence of antibodies in patients on concurrent corticosteroids and immunosuppressive therapy. Infusion reactions occurred in 61 of 993 (6%) infusions in group II and in 45 of 1033 (4%) of infusion in group III. Infusion reactions occurred in 42 of 254 (16%) of infusions in subjects with antibodies to infliximab, compared with 55 of 656 (8%) in those without antibodies. There tended to be fewer infusion reactions in those patients receiving both corticosteroids and immunosuppressants. The incidence of serious infections was similar across all treatment groups. There was no significant difference in the incidence of serious adverse events requiring discontinuation of infusion between those receiving a single infusion and those receiving multiple infusions. The authors concluded that patients with Crohn’s disease who respond to an initial dose of infliximab are more likely: 1) to be in remission at wk 30 and 54; 2) to discontinue corticosteroids; and 3) to maintain their response for a longer period of time, when infliximab treatment is maintained every 8 wk.