Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease

Background & Aims: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). Methods: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to < 150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-κB (NF-κB) system was assessed in biopsy specimens. Results: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 μg, 18% [9.6-29.2]; 4 μg, 20% [11.3-32.2]; 8 μg, 20% [11.1-31.8]; 20 μg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-μg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-κB p65 activation in contrast to nonresponders. Conclusions: Up to 8 μg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-μg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.