B-Cell Depletion
Abstract 2122: HuMax-CD20, a Novel Fully Human Monoclonal IgG1 Antibody in the Treatment of Rheumatoid Arthritis
Authors: M. Østergaard, C Wiell, S Sierakowski, D Wallace, H Kastberg, J Petersen, PT Dawes.
METHODS: This is an ongoing multinational double-blind, randomized, placebo controlled multi center phase I/II trial of HuMax-CD20, (ofatumumab) a human monoclonal IgG1 antibody, in patients with active RA, who previously failed one or more DMARDs. The early safety results of this study were also presented at EULAR 2006. Patients received two infusions of either HuMax-CD20 (300, 700 or 1000 mg) or placebo 2 weeks apart with a dose escalation phase. Preinfusional steroid administration was given the day before the drug was received after several early patients had significant infusion reactions.
RESULTS: 39 patients were treated with mean age 53, mean duration of RA 12 years, 92% RF positive, 13-20 median tender joints and 10-16 swollen joints. Even with premedication with steroids, infusions reactions (urticaria, anyphylactoid, and bronchospasm) occurred in some patients.
| 24 week clinical response rates per dose group (ITT with LOCF) | ||||
| Placebo | 300 mg | 700 mg | 1000 mg | |
| N | 7 | 12 | 10 | 10 |
| ACR20, % of pts | 0 | 50 | 70 | 70 |
| ACR50, % of pts | 0 | 25 | 40 | 40 |
| ACR70, % of pts | 0 | 17 | 20 | 10 |
|
EULAR % of pts Good Moderate |
0 29 |
25 50 |
20 50 |
20 60 |
CONCLUSION: This study demonstrates significant efficacy from this dose ranging study of HuMax CD20. The infusion related events however were significant, even with steroid premedication.
EDITORIAL COMMENT: While these results are certainly encouraging for efficacy, the significant infusion reactions, even with steroid premedication, are concerning. Given that these reactions are occurring using a fully human molecule further supports that idea that infusion reactions (sometimes significant) may be related to CD-20 mediated cell depletion in general and not an effect of the method of depletion.
