Human Anti-Tumor Necrosis Factor Antibody Adalimumab in Crohn's Disease – First Results in Clinical Practice

Introduction: Adalimumab (Humira; Abbott Laboratories, Chicago) represents a human IgG1 monoclonal antibody with high affinity binding and specificity to soluble human tumor necrosis factor (TNF). It has shown efficacy in patients with rheumatoid arthritis. So far, there is only limited clinical experience utilizing this antibody in patients with Crohn's disease (CD). Here we present our results on CD patients treated with Adalimumab for severe CD, collected in a university hospital setting at our IBD clinic in Munich. Aims & Methods: 11 patients with severe steroid-refractory CD and a median age of 40 years (24–73) were treated with adalimumab between July 2005 and May 2006 after failure (n=3), loss of efficacy (n=2), or side effects (n=6) of an earlier infliximab therapy. The median Crohn's disease activity index (CDAI) of the patients before starting therapy was 210 (50–280). The dose regimen was 160mg adalimumab subcutaneously (s.c.) in week 0, followed by 80mg s.c. every two weeks. In three patients, the adalimumab was reduced to 40mg s.c. every two weeks. Patients were seen on a regular base at the IBD outpatient service and the severity of diseases was assessed based on CDAI and laboratory parameters of inflammation (leukocyte count, CRP). Results: In 4 of 10 patients treated with adalimumab, ongoing remission was induced or maintained (median CDAI 10, 0–28); in one patient with adverse events to Infliximab medical treatment with adalimumab generated a maintained stable disease (CDAI 175). In two patients adalimumab therapy was not effective and stopped after 1 month. In four recently treated patients an initial clinical response (decrease of CDAI >70) was documented; however observation time is still too short (4 weeks) to judge upon effectiveness. In general, treatment was well tolerated without serious complications or hospital admissions. 3 of 9 patients noticed the onset of very dry skin within the first 2 weeks of treatment; this side effect however resolved in all patients over the next 4 weeks.

Conclusion: In patients with Crohn's disease intolerant or refractory to infliximab, adalimumab may be an alternative therapy as has recently been hinted in first clinical observations. However, further experience from larger cohorts is clearly required.