OP0119 LONG-TERM SAFETY DATA FROM EXTENDED FOLLOW-UP AND REPEAT USE OF RITUXIMAB IN RHEUMATOID ARTHRITISR. van Vollenhoven1, P. Emery2, C. Bingham3, E. Keystone4, M. Greenwald5, L. W. Moreland6, M. Sweetser7, K. Rowe8, B. Wagner9, F. Magrini8
1Rheumatology, Karolinska University Hospital, Stockholm, Sweden, 2Rheumatology, Leeds General Infirmary, Leeds, United Kingdom, 3Rheumatology, Johns Hopkins University, Baltimore, MD, United States, 4Rheumatology, University of Toronto, Toronto, ON, Canada, 5Desert Medical Advances, Palm Desert, CA, 6Rheumatology, University of Alabama School of Medicine, Birmingham, AL, 7Drug Safety and Risk Management, Biogen Idec, Cambridge, MA, United States, 8Medical Sciences, Roche Products Ltd, Welwyn Garden City, United Kingdom, 9Drug Safety, Genentech Inc, South San Francisco, CA, United States
Objectives: To evaluate the long-term safety of single and multiple courses of rituximab (RTX) in patients (pts) with active rheumatoid arthritis (RA).
Methods: A further safety analysis of pts exposed to RTX in the ongoing clinical programme was performed. The current analysis includes data on all pts receiving up to 4 treatment courses.
Results: As of September 2006, a total of 1053 RA pts had been exposed to RTX in the clinical programme; total duration of exposure was 2438 pt-years (yrs) with 700 pts followed-up for >2 yrs and 120 pts for >3 yrs, receiving up to 7 treatment courses. We report here safety information for Courses 1–4 (C1–4) wherein 684, 400 and 142 pts received ≥2, ≥3 and ≥4 courses of RTX, respectively. Overall, the incidence of adverse events (AEs) decreased from 88% (931/1053) of RTX pts after C1 to 81%, 72% and 65% following C2, C3 and C4, respectively (Table). Serious AEs (SAEs) also followed a similar pattern (Table). Acute infusion reactions upon first infusion of each course decreased steadily from 23% (C1) to 11% (C4) and incidence with the second infusion of each course decreased from 7% (C1) to 2% (C2). A total of 702 pts (67%) experienced ≥1 infection. The most common infections were upper respiratory tract infections, including nasopharyngitis (32%), and urinary tract infections (11%). The proportion of pts with IgM and IgG levels below the lower limit of normal increased with further treatment courses. Additional analyses are ongoing evaluating the potential relationship between the immunoglobulin levels and non-serious/serious infections. In this series, opportunistic infections, viral reactivations or tuberculosis were not reported. A total of 36 high- and low-grade malignancies (18 in C1, 13 in C2, 4 in C3 and 1 in C4) occurred in 32 pts (3%), of which 4 had a fatal outcome (duodenal cancer, adenocarcinoma, pancreatic cancer, myelodysplastic syndrome). No lymphoproliferative malignancies and no increased risk of malignancy with additional courses of treatment were observed.
Table:
| 1st course
(n=1053) | 2nd course
(n=684) | 3rd course
(n=400) | 4th course
(n=142) |
|
Any AE
n (%) | 931 (88) | 553 (81) | 228 (72) | 93 (65) |
Serious AE
n (%) | 187 (18) | 105 (15) | 39 (10) | 4 (3) |
| No. of infections | 1083 | 608 | 260 | 75 |
Infections/100 pt-yrs
(CI) | 79.46 (74.87–84.34) | 84.76 (78.28–91.77) | 96.97 (85.87–109.50) | 101.4 (80.86–127.15) |
No. of serious
infections | 73 | 33 | 17 | 4 |
Serious infections
/100 pt-yrs (CI) | 5.36 (4.26-6.74) | 4.6 (3.27-6.47) | 6.34 (3.94-10.20) | 5.41 (2.03-14.41) |
|
| CI=confidence interval |
Conclusion: This further update on the long-term follow-up (2438 pt-yrs) of RA pts receiving RTX showed a safety profile consistent with that reported previously. After 4 courses, a slight upward trend was observed in the rate of infections; however, the rate of serious infections remained stable with repeated treatment.
