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Clinical Trial
. 2011;13(5):R141.
doi: 10.1186/ar3455. Epub 2011 Sep 1.

Integrated safety in tocilizumab clinical trials

Michael H Schiff  1 , Joel M Kremer, Angelika Jahreis, Emma Vernon, John D Isaacs, Ronald F van Vollenhoven
Affiliations
Clinical Trial

Integrated safety in tocilizumab clinical trials

Michael H Schiff et al. Arthritis Res Ther. 2011.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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).

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Figures

Figure 1
Figure 1
Summary of clinical trials and patients in the all-exposed population. aDoes not include patients from study 1; bExtension studies are ongoing; most patients receive 8 mg/kg TCZ + MTX/DMARDs; cAll patients who received TCZ treatment; from their first dose (either in a core or an extension study) up to a cutoff date of February 6, 2009. DMARD-IR, inadequate responder to disease-modifying antirheumatic drugs; MTX, methotrexate; study 1, clinical pharmacology study; study 2, AMBITION; study 3, RADIATE; study 4, TOWARD; study 5, OPTION, study 6, LITHE; TCZ, tocilizumab; TNF-IR, inadequate responder to tumor necrosis factor inhibitor.
Figure 2
Figure 2
Rates of serious infections (95% confidence intervals) in the all-exposed population by 6-month periods. PY, patient-years. Multiple occurrences of the same adverse event in a patient in a 6-month period were counted as individual events.
See this image and copyright information in PMC

References

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