Integrated safety in tocilizumab clinical trials
1 Rheumatology Division, University of Colorado School of Medicine, 5400 South Monaco Street, Greenwood Village, CO 80111, USA
2 Center for Rheumatology, Albany Medical College, State University of New York, 1367 Washington Avenue, Albany, NY 12206, USA
3 Product Development Inflammation, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
4 PDBB-Biostatistics, Roche Products Ltd., Hexagon Place, 6 Falcon Way, Shire Park, Welwyn Garden City, UK AL7 1TW
5 Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University and Freeman Hospital, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
6 Rheumatology Department, Karolinska Institute, Solnavägen 1, Solna, Alfred Nobels Allé 8, Huddinge, SE-171 77 Stockholm, Sweden
Citation and License
Arthritis Research & Therapy 2011, 13:R141 doi:10.1186/ar3455Published: 1 September 2011
The efficacy and safety of tocilizumab in patients with rheumatoid arthritis have been evaluated in a comprehensive phase 3 program. Patients from these randomized trials could receive tocilizumab treatment in open-label extension trials. Here, the long-term safety profile of tocilizumab, using pooled data from all of these trials, is reported.
Cumulative safety data (as of February 6, 2009) from five core phase 3 trials, two ongoing extension trials, and one clinical pharmacology study were analyzed. Two patient populations were evaluated: an all-control population (n = 4,199), which included all patients randomly assigned in the placebo-controlled portions of the five core studies, and an all-exposed population (n = 4,009), which included patients from any of the eight studies who received at least one dose of tocilizumab.
Total exposure to tocilizumab was 8,580 patient years (PY), and total duration of observation was 9,414 PY. Overall adverse event (AE) and serious AE (SAE) rates were 278.2/100 PY and 14.4/100 PY, respectively. These events included serious infections (4.7/100 PY), opportunistic infections (0.23/100 PY), gastrointestinal perforations (0.28/100 PY), malignancy (1.1/100 PY), myocardial infarction (0.25/100 PY), and stroke (0.19/100 PY). The rates of SAEs and serious infections were stable over time; no increase with prolonged exposure was noted.
The longer-term safety profile of tocilizumab (mean treatment duration, 2.4 years) is consistent with that observed in the phase 3 studies (duration up to 1 year).