Natalizumab, a humanized monoclonal Immunoglobulin G4 antibody to 4 integrin, was investigated as a treatment of active Crohn's disease.
Dr Bruce Sands and colleagues from Massachusetts assessed the safety of natalizumab given in combination with infliximab.
The investigative team evaluated 79 adult patients with active Crohn's Disease despite ongoing infliximab treatment.
The team randomized 52 patients to receive 3 intravenous infusions of 300 mg natalizumab, and 27 patients to placebo every 4 weeks.
Patients received infliximab 5 mg/kg every 8 weeks for at least 10 weeks before randomization and throughout the study.
|4% patients developed anti-natalizumab antibodies|
|Inflammatory Bowel Disease|
The investigators' primary objective was to assess the short-term safety, and tolerability of natalizumab in patients concurrently receiving infliximab.
Secondary and tertiary objectives included measures of efficacy, health-related quality of life, and effects on inflammatory markers.
A subset of patients also participated in a pharmacokinetic/pharmacodynamic analysis of the effects of concurrent treatment.
The investigators found that incidence of adverse events was similar in the treatment groups.
Adverse events frequently reported in both groups were headache, Crohn's Disease exacerbation, nausea, and nasopharyngitis.
The investigative team noted that no patient had a hypersensitivity-like reaction to natalizumab.
However, about 5% of patients experienced reactions to infliximab.
The investigators observed that 4% patients developed anti-natalizumab antibodies.
The team identified 14% of patients who developed anti-infliximab antibodies.
The mean Crohn's Disease Activity Index score decreased with natalizumab plus infliximab but was unchanged with infliximab alone.
Patients in both groups showed small increases in health-related quality of life.
The investigators noted no drug-drug interactions.
Dr Sands' team concludes, “The combination of natalizumab plus infliximab was well tolerated.”
“Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone.”