Human Anti-TNF Monoclonal Antibody Adalimumab: Open-Label Study
Background: We assessed the tolerability and clinical benefit of adalimumab, a human antibody to tumor necrosis factor (TNF), in patients with Crohn's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab, but who no longer had a sustained response and/or tolerance to infliximab.
Methods: A total of 24 patients with Crohn's disease who had lost responsiveness or developed intolerance (acute or delayed infusion reactions) to infliximab were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2. After week 4, the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission, complete fistula closure, and complete steroid withdrawal. Outcome measures included the ability to tolerate adalimumab and clinical remission (defined as a Crohn's disease activity index (CDAI) score ≤150 points) and clinical response (defined as a decrease in the CDAI) ≥100 points) in patients who had a baseline CDAI score ≥220.
Results: None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab (including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab). Of 17 patients with baseline CDAI scores ≥220: clinical remission occurred at weeks 4 and 12 in 2 (12%) and 5 (29%), respectively; and clinical response occurred in 7 (41%) and 10 (59%), respectively. Nineteen patients (79%) escalated their dose during weeks 4-6.
Conclusions: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with Crohn's disease who have previously lost their response to, or cannot tolerate infliximab.

The chimeric monoclonal antibody to tumor necrosis factor (TNF)-, infliximab, is effective for both the short- and long-term treatment of patients with moderate to severe Crohn's disease including patients with draining enterocutaneous fistulas. However, infliximab is immunogenic and intermittent administration results in human anti-chimeric antibodies (HACAs, also known as antibodies to infliximab) that lead to infusion reactions, loss of efficacy, and delayed hypersensitivity reactions.

Human monoclonal antibodies are relatively less immunogenic than chimeric monoclonal antibodies. Adalimumab (Humira, Abbott Laboratories, Parsippany, New Jersey) is a recombinant human IgG1 monoclonal antibody compromised of fully human heavy and light chain variable regions, which confer specificity to human TNF, and human IgG1 heavy chain and kappa light chain sequences. Adalimumab binds with high affinity and specificity to soluble TNF- but not lymphotoxin (TNF-ß). Adalimumab 40 mg every other week, with or without disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate, is effective for the treatment of rheumatoid arthritis, and the dose can be escalated to 40 mg weekly in patients not on concomitant DMARDs who have not responded or have had an incomplete response. We conducted a 12-wk phase 2a trial in patients with Crohn's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab, but who no longer had a sustained response and or had become intolerant to infliximab.