Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Long-Term Safety of Rituximab: Follow-Up of the Rheumatoid Arthritis Clinical Trials and Retreatment Population.

van Vollenhoven5,  Ronald, Emery2,  Paul, Bingham4,  Clifton O., Keystone9,  Edward C., Fleischmann8,  Roy M., Furst7,  Daniel E., Macey6,  Katherine

Biogen Idec Inc
Chapel Allerton Hospital, Leeds, United Kingdom
Genentech Inc
Johns Hopkins University, Baltimore, MD
Karolinska Institute, Stockholm, Sweden
Roche Products Ltd
University of California Los Angeles Medical School, Los Angeles, CA
University of Texas Southwestern Medical Center, Dallas, TX
University of Toronto, Toronto, ON, Canada

Objective:

To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients (pts) in clinical trials.

Methods:

Pooled observed case analysis of safety data from pts treated with RTX plus methotrexate (MTX) in a global clinical trial program. Pts were offered RTX retreatment based on physician decision of clinical need and the criteria for retreatment included assessment of active disease (defined as either SJC and TJC >=8 or DAS28 >=2.6). Pts who received placebo during placebo-controlled study periods were pooled to provide a placebo population.

Results:

As of September 2009, 3189 pts had been treated with RTX providing 9342 pt-yrs exposure. The analysis includes >9 yrs of follow-up with up to 15 courses of RTX. More than 1500 pts were followed for >3 yrs and 587 pts for >5 yrs with 1724, 1392, 1036 and 656 pts receiving >=3, >=4, >=5 and >=6 courses, respectively. Other than infusion-related reactions (IRR), the safety profile of RTX was similar to the placebo population or general RA populations. In the RTX group, the most frequent adverse event (AE) was IRR; most were CTC grade 1 or 2 and occurred after the first infusion of the first course (23.0%), with 0.5% considered serious (over all courses). Rates of serious AEs (SAEs) and infections generally remained stable over time and over multiple RTX courses, and in patients in long-term follow-up (>5 yrs).

The overall serious infection rate was 4.35 events/100 pt-yrs (3.19 events/100 pt-yrs in pts treated for >5 yrs) and was comparable to that observed in the placebo population (4.29 events/100 pt-yrs). The most frequent serious infections were of the lower respiratory tract, predominantly pneumonia (2%). Serious opportunistic infections were rare with the rate comparable to the placebo population (0.04/100 pt-yrs in RTX all exposure compared to 0.1/100 pt-yrs in pooled placebo). Rates of myocardial infarction (0.49 events/100 pt-yrs) and stroke (0.25 events/100 pt-yrs) were consistent with rates in the general RA population (0.34–0.59 events/100 pt-yrs and 0.112–0.76 events/100 pt-yrs, respectively).1–4

Conclusions:

In long-term follow-up of RA pts treated with RTX in clinical trials, no new safety signals were observed in all exposed pts, or in pts with >5 yrs exposure. RTX has remained generally well tolerated over time and over multiple courses, with a safety profile similar to that of the pooled placebo population and consistent with published data on pts with moderate to severe RA.

 All exposure (n = 3188) 9342 pt-yrsLong term (>5 yrs) (n = 587) 3386 pt-yrsPooled placebo (n = 818) 575 pt-yrs
AE rate/100 pt-yrs (95% CI)309.4 (305.9–313.0)285.1 (279.5–290.9)353.1 (341.5–365.0)
SAE rate/100 pt-yrs (95% CI)16.2 (15.4–17.0)15.5 (14.2–16.9)15.5 (13.2–18.2)
Infection rate/100 pt-yrs (95% CI)94.3 (92.3–96.3)83.2 (80.2–86.3)100.8 (94.7–107.3)
Serious infection rate/100 pt-yrs (95% CI)4.35 (3.94–4.79)3.19 (2.64–3.85)4.29 (3.17–5.80)

1.Pharmetrics Claims Database, 2006.

2.British Society for Rheumatology Biologics Register, 2007.

3.Nurses' Health Study, 2003.

4.General Practice Research Database, 2003.

To cite this abstract, please use the following information:
van Vollenhoven, Ronald, Emery, Paul, Bingham, Clifton O., Keystone, Edward C., Fleischmann, Roy M., Furst, Daniel E., et al; Long-Term Safety of Rituximab: Follow-Up of the Rheumatoid Arthritis Clinical Trials and Retreatment Population. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :391
DOI: 10.1002/art.28160

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