Background/Purpose: The safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) has been reported in previous pooled analyses of clinical trials. An update of long-term safety data of CZP in RA with a cut-off date of 30 Nov 2011 is provided.

Methods: The pooled analysis included 10 completed randomized controlled trials (RCTs) of CZP in RA and their open-label extensions (OLEs). Pooling was done across all doses. Some patients (pts) received CZP 400 mg Q2W (twice the registered dose) as per protocol. Adverse events were defined as those occurring after first dose and within a maximum of 84 days of last dose. Serious adverse events (SAEs) were defined conservatively by the regulatory definition¹ with the addition of opportunistic infections (OIs), malignancies and medical events important to the investigator. Serious infectious events (SIEs) were defined according to the regulatory definition with addition of the need for IV antibiotics. Search terms for OIs were defined by 6 external experts and validated by the steering committee (JC, VB, RVV and XM). All cases of death, SIEs (including OIs) and malignancies were manually reviewed by external experts, classified according to pre-defined standard procedures and validated by the study authors. Deaths were categorized as primarily associated with cardiovascular (CV), infectious, malignant or other causes; malignancies were classified as non-melanoma skin cancer (NMSC), solid tumors or lymphoma. Incidence rates (IR) and event rates (ER) per 100 pt-years (PY) are presented.

Results: By 30 Nov 2011, 4049 RA pts had received CZP in all studies (RCTs and OLEs) for a total of 9277 PY. Mean exposure to CZP in all studies was 2.1 yrs (Y) (min 0.04, max 7.6); median exposure was 0.7 Y. SIEs were the most common SAEs. In total, 43 tuberculosis (TB) infections occurred in 43 pts, of which 39 occurred in Central and Eastern Europe (CEE). 58 deaths occurred in CZP pts (IR: 0.63/100 PY) as a result of 19 CV events, 13 infections, 13 malignancies and 18 other causes. 65 CZP pts in all studies developed malignancies (ER: 0.72/100 PY), with 60 pts developing solid tumors (ER: 0.67/100 PY) and 5 developing lymphoma (0.05/100 PY).

Conclusion: No new safety signals associated with CZP have emerged in this updated long-term safety analysis. While SIE rates were higher for CZP than for PBO in the RCTs, they did not increase with continued exposure to CZP. Due to the shorter duration of PBO treatment compared with CZP, comparisons between the CZP and PBO groups should be interpreted cautiously. TB incidence may be explained by high recruitment in CEE prior to 2007. The rates of malignancies and serious infections are in line with CZP data reported in the product label and anti-TNF registry data.^2,3

References

1. http://www.fda.gov/Safety/MedWatch/HowToReport/ucm053087.htm

2. Dixon et al. Arth Care Res. 2010;62:755.

3. Galloway et al. Rheumatol. 2011;50:124.

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