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Meta-Analysis
. 2009 Dec;68(12):1863-9.
doi: 10.1136/ard.2008.102103. Epub 2009 Jan 15.

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases

G R Burmester  1 , P Mease, B A C Dijkmans, K Gordon, D Lovell, R Panaccione, J Perez, A L Pangan
Affiliations
Meta-Analysis

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases

G R Burmester et al. Ann Rheum Dis. 2009 Dec.

Abstract

Objectives: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population.

Methods: This analysis included 19,041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization.

Results: Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population.

Conclusions: Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit-risk profile.

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Conflict of interest statement

Competing interests: JP and ALP are employees of Abbott Laboratories. GRB has served as a consultant with Abbott Laboratories, Essex/Schering-Plough, Novartis, Roche and has received grants from Abbott Laboratories, Essex/Schering-Plough, Novartis, Roche, Wyeth and honoraria from Abbott Laboratories, Essex/Schering-Plough, Novartis, Roche and Wyeth. BACD has served as a consultant with Abbott, Centocor, Schering-Plough and has received grants from Abbott, Centocor, Schering-Plough and received honoraria from Abbott, Centocor and Schering-Plough. KG has served as a consultant with and has received grants and honoraria from Abbott Laboratories. DL has served as a consultant with Abbott Laboratories, Amgen, Centocor, Hoffmann-La Roche, Novartis, Pfizer, Regeneron, Xoma and has received grants from Abbott Laboratories, Amgen, Bristol-Myers Squibb, Centocor, Hoffmann-La Roche, Regeneron, Roche and honoraria from Wyeth Pharmaceuticals. RP has served as a consultant with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Centocor, Elan, Ferring, GlaxoSmithKline, Procter and Gamble, Schering-Plough, Shire, UCB and has received grants from Abbott Laboratories, Axcan, Bristol-Myers Squibb, Centocor, Elan, Millennium, Procter and Gamble and has received honoraria from Abbott, Astra Zeneca, Byk Solvay, Centocor, Elan, Janssen, Procter and Gamble, Prometheus, Schering-Plough and Shire. PM has received grants and honoraria from Abbott Laboratories.

Figures

Figure 1
Figure 1
(A) Time to first serious infection, all adalimumab patients. (B) Time to first malignancy other than non-melanoma skin cancer (NMSC), all adalimumab patients. Overall scales are from 1.0 to 0.0; the portion of the scale from 0.7 to 1.0 has been emphasised for clarity. Numbers along the x-axis represent the numbers of patients who were at risk for each time point, ie, those still in the study who had not yet experienced the event.
Figure 2
Figure 2
Standardised incidence rates (SIR) for all malignancies and lymphomas for rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), psoriasis (Ps) and Crohn’s disease (CD). *All malignancies other than non-melanoma skin cancer. †Based on data from 12 344 patients. All other diseases included all the patients in the analysis. ‡No lymphomas were observed in psoriasis. No malignancies were observed in juvenile idiopathic arthritis.
Figure 3
Figure 3
Standardised incidence rates (SIR) for non-melanoma skin cancer (NMSC) using three comparator databases. *Based on data from 12 344 patients. All other diseases included all the patients in the analysis. No malignancies were observed for juvenile idiopathic arthritis. AS, ankylosing spondylitis; CD, Crohn’s disease; NCI, National Cancer Institute; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
Figure 4
Figure 4
Standardised mortality rates (SMR) for rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (Ps) and Crohn’s disease (CD). No deaths occurred in juvenile idiopathic arthritis or ankylosing spondylitis. *No deaths occurred among female patients with psoriasis.
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