Article Text

Extended report
Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials
  1. V P Bykerk1,
  2. J Cush2,
  3. K Winthrop3,
  4. L Calabrese4,
  5. O Lortholary5,
  6. M de Longueville6,
  7. R van Vollenhoven7,
  8. X Mariette8
  1. 1Hospital for Special Surgery, New York, New York, USA
  2. 2Baylor Research Institute and Baylor University Medical Center, Dallas, Texas, USA
  3. 3Oregan Health and Science University, Portland, Oregon, USA
  4. 4Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, Ohio, USA
  5. 5IHU Imagine, Université Paris Descartes, Hôpital Necker Enfants malades, Paris, France
  6. 6UCB Pharma SA, Brussels, Belgium
  7. 7Department of Rheumatology, Karolinska Institute, Stockholm, Sweden
  8. 8Université Paris-Sud, AP-HP, Hôpitaux universitaires Paris-Sud, Paris, France
  1. Correspondence to Dr Vivian P Bykerk, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA; BykerkV{at}HSS.EDU

Abstract

Objective To report the long-term safety data of certolizumab pegol (CZP) in rheumatoid arthritis (RA) accumulated as of 30 November 2011.

Design Data from 10 completed randomised controlled trials (RCT) of CZP in RA and several open-label extensions (OLE) were pooled across all doses. Reported adverse events (AE) occurred between the first dose and 84 days after the last dose. All deaths, serious infectious events (SIE) and malignancies were reviewed by external experts, classified according to predefined rules, and validated by an external steering committee. Incidence rates (IR) and event rates (ER) per 100 patient-years (PY) are presented.

Results 4049 RA patients who received CZP were included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years (range 0.04–7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most common serious AE, occurring more frequently in CZP compared to placebo-treated patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65 to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER 4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and 70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY), including five lymphomas (IR 0.05/100 PY).

Conclusions No new or unexpected safety signals associated with CZP emerged in this updated long-term safety analysis. While SIE rates were higher for CZP than for placebo in RCT, the rate decreased with continued exposure to CZP. These rates are consistent with data previously reported for CZP and other tumour necrosis factor inhibitors.

  • Anti-TNF
  • Rheumatoid Arthritis
  • Infections
  • Tuberculosis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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