Abstract 2086: Ofatumumab, a Human CD20 Monoclonal Antibody, in the Treatment of Rheumatoid Arthritis: Early Results from an Ongoing, Double-Blind, Randomized, Placebo Controlled Clinical Trial
Authors
M Østergaard, B Baslund, W Rigby, B Rojkovich, C Jorgensen, J Petersen, H Kastberg, P Dawes, S Sierakowski
Background:
Ofatumumab is a fully human monoclonal anti-CD20 antibody. We have previously reported interim results on the first 39 patients enrolled in the study at ACR 2006 and EULAR 2006. At ACR 2007 the 24 week results from the first 100 patients enrolled in the Phase II study were reported.
Methods:
225 patients with active RA, who had previously failed one or more DMARDs, received two infusions of either ofatumumab (300, 700 or 1000 mg) or placebo 2 weeks apart. Continuation of ongoing therapy with stable doses of methotrexate and ≤10 mg/day prednisolone and previous exposure to biological agents were allowed, except for CD20 antibodies within 2 years prior to inclusion. Patients were premedicated with paracetamol, antihistamine and glucocorticoid.
Results:
Data from the first 100 patients at 24 weeks were reported. Statistically significantly more patients on ofatumumab obtaining ACR20 compared to patients on placebo (Fisher’s exact test; p=0.012, p=0.003 and p=0.009 in the 300, 700 and 1000 mg groups) (Table). Also, good or moderate EULAR response was seen in 21 (78%), 17 (71%) and 16 (64%) of patients on ofatumumab and 7 (30%) of patients on placebo (p=0.001, p=0.009, p=0.020). In the PP population comprising 74 patients at week 24 (25 patients were excluded due to: insufficient administration of study drug (9), disallowed medication (12), or other reasons (4)) the ACR20 responses were 46%, 71% and 69% in the three dose groups and 12% in the placebo group (p=0.039, p=0.001, p=0.001). Of the first 53 patients included in the study, 3 patients had serious infusion related reactions (SIRRs) of whom one had a serious bronchospasm. The infusion rate was decreased for the next 47 patients where only one SIRR was reported. All patients have recovered from these adverse events. No patients developed human anti-human antibodies. Rapid and sustained peripheral CD19+ B-cell depletion was seen in all ofatumumab dose groups.
Baseline demographics and 24 week clinical response rates per dose group (ITT population) |
||||
|
Placebo |
300 mg |
700 mg |
1000 mg |
N |
23 |
27 |
24 |
25 |
Age, years, median |
51 |
52 |
52 |
49 |
Duration of RA years, median |
7 |
8 |
6 |
7 |
RF positivity, % of pts |
87 |
85 |
96 |
96 |
Concomitant MTX % of pts [median weekly dose, mg] |
83 [15] |
74 [13] |
75 [15] |
72 [15] |
Concomitant Prednisolone % of pts [median daily dose, mg] |
48 [10] |
89 [8] |
67 [8] |
48 [10] |
Prior treatment with TNFalpha- inhibitors, % of pts |
29 |
30 |
29 |
36 |
DAS28, median |
5.49 |
5.57 |
5.65 |
5.44 |
ACR20 response,% of pts |
9 |
41 |
50 |
44 |
EULAR response, % of Good [Moderate] |
4 [26] |
33 [44] |
17 [54] |
24 [40] |
Editorial Comment:
The results from this study continue to be only interim and do not contain a full dataset. It is hoped that these data will be available in the future. Interpretation of a per protocol (completer) analysis based on only a subset of patients enrolled is difficult. However, the proportion of ACR20 responders is similar to prior studies of anti CD20 molecules. Even though there was an interim change in the protocol to slow infusion rates that has been associated with fewer infusion reaction, the fact that this is occurring with a fully human antibody suggests that infusion reactions are due to acute anti CD20 depletion with antibodies rather than the chimeric or humanization of the construct.
