Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: This analysis evaluated the long-term safety of rituximab (RTX) in RA patients (pts) in a global clinical trial program.
Methods: Pooled observed case analysis of safety data from pts with moderate to severe active RA treated with RTX+MTX. Pts were retreated based on physician’s determination of clinical need and evidence of active disease (defined as either SJC and TJC ≥8 or DAS28 ≥2.6). Subgroup analysis of pts with follow-up >5 yrs was undertaken. Pooled data from pts who received placebo during placebo-controlled study periods were also analyzed.
Results: As of Sep 2011, 3595 pts (All-Exposure population) had received ≤19 courses of RTX over the 10-yr observation period (14008 pt-yrs). Of these pts, 1145 had follow-up >5 yrs (7716 pt-yrs) (>5 yr). The placebo population comprised 818 pts (1107 pt-yrs) with a mean follow-up of 1–1.5 yrs. In the All-Exposure population, infusion-related reaction (IRR) was the most frequent adverse event (AE); most were grade 1 or 2, were rarely serious, and generally occurred following the 1st infusion of the 1st course (789/3595 pts; 22%). Rates of AEs, serious AEs (SAEs), and infections were comparable across analysis populations and generally remained stable over time and multiple courses (Table). Overall serious infection (SIE) rates in the RTX All-Exposure and >5 yr sub-population were comparable to that observed in the placebo population. Pneumonia was the most frequently reported SIE (2% of RTX pts). There were no cases of hepatitis B reactivation. Two cases of pulmonary tuberculosis (TB), treated with anti-TB medication, occurred in the All-Exposure population, as reported previously.1 No cases of extra-pulmonary TB, atypical mycobacterial infection, or multidrug-resistant TB were reported. Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX pts vs 0.09/100 pt-yrs in placebo). No further cases of PML in the RA clinical trial program have been reported other than the single case previously described.2 No increased risk of malignancy over time or course was evident, and MI rates (0.40/100 pt-yrs) were consistent with rates in the general RA population (0.48–0.59/100 pt-yrs).3
| RTX All-Exposure (n=3595) 14008 pt-yrs |
RTX Long-term (>5 yrs) (n=1145) 7716 pt-yrs |
Pooled placebo (n=818) 1107 pt-yrs |
|
| AEs | 249.34 (246.74–251.97) | 237.25 (233.83–240.71) | 315.43 (305.14–326.06) |
| SAEs | 14.03 (13.42–14.66) | 12.25 (11.49–13.05) | 13.82 (11.79–16.19) |
| Infections | 78.60 (77.14–80.08) | 75.10 (73.19–77.06) | 90.39 (84.96–96.17) |
| Serious infections | 3.80 (3.50–4.14) | 2.76 (2.41–3.16) | 3.79 (2.80–5.13) |
Conclusion: These long-term data from 3595 pts treated with RTX over 10 yrs (14008 pt-yrs) of follow-up in clinical trials confirm that RTX remains well tolerated over time and multiple courses with a consistent safety profile. No new safety signals were observed with increasing duration of exposure, including within a subgroup of pts with >5 yrs’ follow-up. Apart from IRRs, the overall safety profile of RTX remains similar to that of the pooled placebo population and is consistent with published data for moderate to severe RA and with previous analyses of this pt cohort.
1. van Vollenhoven RF et al. Arthritis Rheum 2011;63(10):S857
2. Fleischmann RM. Arthritis Rheum 2009;60:3225
3. British Society for Rheumatology Biologics Register, 2007
Disclosure:
R. F. van Vollenhoven,
Abbott, GSK, Merck, Pfizer, Roche, UCB, BMS, HGS,
2,
Abbott, GSK, Merck, Pfizer, Roche, UCB, BMS, HGS,
5;
P. Emery,
Pfizer, Merck, Abbott, BMS, Roche, UCB,
5;
C. O. Bingham III,
Roche, Genentech, Biogen/IDEC,
2,
Roche, Genentech,
5;
E. Keystone,
Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB,
2,
Abbott, AstraZeneca, Biotest, Bristol-Meyers Squibb, Centocor, Roche, Genentech, Merck, Nycomed, Pfizer, UCB,
5;
R. Fleischmann,
Genentech Inc,, Roche, Abbott, Amgen, UCB, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen,
2,
Roche, Abbott, Amgen, UCB, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, Novartis, Astellas, Astra-Zeneca, Jansen, HGS,
5;
D. Furst,
Abbott, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
2,
Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, CORRONA, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
5,
Abbott, Actelion, UCB (CME ONLY),
8;
N. Tyson,
Roche,
1,
Roche ,
3;
A. Mehbob,
Roche,
3;
P. B. Lehane,
Roche,
3.
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