Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial.
OBJECTIVE
To assess the efficacy and safety of 1 versus 2 courses of rituximab over 48 weeks in patients with rheumatoid arthritis (RA).


METHODS
Adult patients taking methotrexate with a previous inadequate response to > or = 1 tumor necrosis factor inhibitor received 1 course of open-label rituximab (2 x 1000 mg IV) at baseline. From Week 24, patients were randomized to receive an additional course of retreatment with rituximab or placebo. Efficacy responses at Week 48 relative to baseline were assessed.


RESULTS
Of 559 patients who received the open-label first course of rituximab, 475 patients were randomized to a second course (rituximab retreatment: n = 318, placebo retreatment: n = 157). Relative to baseline, patients who took rituximab during retreatment had significantly improved efficacy at Week 48 compared to patients who took a placebo during retreatment [American College of Rheumatology (ACR20) criteria, 54% vs 45%, p = 0.02; change in Disease Activity Score-28 mean -1.9 vs -1.5, p = 0.006]. Differences in efficacy between groups were first observed following Weeks 28-32. Worsening of most components of the ACR core set occurred in the placebo-retreated patients with relative maintenance of these measures in rituximab-retreated patients. Randomized patients who had achieved week 24 ACR responses following the first course had greater odds of losing response if retreated with placebo (odds ratios for ACR20, ACR50, ACR70: 2.09, 2.03, and 4.09, respectively). Following retreatment, the proportion of patients experiencing any adverse events (AE), serious AE, infections, and serious infections were comparable between the rituximab and placebo retreatment groups.


CONCLUSIONS
Two courses of rituximab about 6 months apart resulted in improved and sustained efficacy at 1 year, compared with 1 course, with a similar safety profile.
Mease
Philip J
PJ
Seattle Rheumatology Associates, Swedish Medical Center, Seattle, WA 98104, USA. pmease@nwlink.com
Cohen
Stanley
S
Gaylis
Norman B
NB
Chubick
Andrew
A
Kaell
Alan T
AT
Greenwald
Maria
M
Agarwal
Sunil
S
Yin
Ming
M
Kelman
Ariella
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016017:Odds Ratio; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D008727:Methotrexate