Abstract 2088: Repeated Treatment Courses of Rituximab Produce Sustained Efficacy in Patients with Rheumatoid Arthritis and an Inadequate Response or Intolerance to One or More TNF Inhibitors
Authors
EC Keystone, RM Fleischmann, P Emery, A Chubick, MR Dougados, AR Baldassare, JM Bathon, E Hessey, D Hagerty, S Cooper
Purpose:
This was a report of longer-term efficacy of repeated courses of rituximab (RTX) therapy in patients with active RA with a prior inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors.
Methods:
Patients received repeated courses of RTX in ongoing open-label extensions to Phase II and III studies. Each course of RTX consisted of two infusions of RTX (1000 mg x 2) 2 weeks apart; prior to each infusion, all pts received 100 mg IV methylprednisolone, with oral glucocorticoids administered between the two infusions. Patients were eligibile for repeat treatment if they had: an initial predefined improvement (≥20% reduction of SJC and TJC), residual disease activity (defined as ≥8 SJC and TJC), in combination with the judgment of the treating physician. Placebo-treated patients could also enroll and receive RTX. This was a completer analysis in which all efficacy outcomes were assessed relative to the original pretreatment baseline.
Results: As of September 2006, 571 RA patients with a prior inadequate response or intolerance to ≥1 TNF inhibitors had been exposed to repeated courses of RTX (1000 mg x 2 for all courses) in the clinical program. Of these, 210 pts had received ≥3 courses (C) of RTX. The median period between treatment courses was 37.9 weeks for C1-C2 and 42.1 weeks for C2-C3. Efficacy data were available for 97 pts who, at the time of analysis, had reached at least 24 weeks’ follow-up post-C3. Comparison of efficacy between treatment courses at 24 weeks following C1, C2, and C3 showed sustained efficacy for all outcomes relative to original baseline.
|
|
Week 24 (n=96 pts) |
|
|
Course 1 |
Course 2 |
Course 3 |
ACR20, n (% of pts) |
66 (69) |
73 (76) |
74 (77) |
ACR50, n (% of pts) |
35 (36) |
46 (48) |
46 (48) |
ACR70, n (% of pts) |
11 (11) |
18 (19) |
24 (25) |
Low disease activity |
11 (11) |
25 (26) |
28 (29) |
Remission |
6 (6) |
14 (14) |
12 (12) |
DAS28 change from original baseline, mean (SD) |
-2.39 |
-2.94 |
-3.10 |
Conclusions
Repeated courses of RTX produced sustained efficacy relative to original baseline in patients with active RA who had responded inadequately to previous TNF inhibitors and who remained on RTX 24 weeks after the third course.
Editorial comment
As with any open label extension study, these results must be interpreted with caution as they represent a completer analysis, thus there is likely a selection for “responders”. In this group of patients who received 3 courses of rituximab however, there was continuing efficacy compared to the original course and increases over time in outcomes. The numbers remain small from these clinical trials and this is a group of patients who were incomplete responders to TNF antagonists and in whom oral and IV steroids were given with each course of therapy. Whether similar results would be seen with other groups of patients and in whom oral corticosteroids were not part of the protocol are needed. It is also unfortunate that there are not better criteria for retreatment available for the drug in terms of timing from original course, or flare of a certain degree.
