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Review
. 2013 Apr;72(4):517-24.
doi: 10.1136/annrheumdis-2011-201244. Epub 2012 May 5.

Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease

Gerd R Burmester  1 , Remo Panaccione, Kenneth B Gordon, Melissa J McIlraith, Ana P M Lacerda
Affiliations
Free PMC article
Review

Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease

Gerd R Burmester et al. Ann Rheum Dis. 2013 Apr.
Free PMC article

Abstract

Background: As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited.

Objective: To analyse the long-term safety of adalimumab treatment.

Methods: This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data.

Results: The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population.

Conclusions: Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.

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Conflict of interest statement

Competing interests: GRB has served as a consultant to Abbott Laboratories, Essex/Schering-Plough, Novartis and Roche and has received grants and honoraria from Abbott, Essex/Schering-Plough, Novartis, Roche, and Wyeth. RP has served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Centocor, Elan, Ferring, GlaxoSmithKline, Procter and Gamble, Schering-Plough, Shire and UCB and has received grants from Abbott, Axcan, Bristol-Myers Squibb, Centocor, Elan, Millennium and Procter & Gamble and honoraria from Abbott Laboratories, Astra Zeneca, Byk Solvay, Centocor, Elan, Janssen, Procter and Gamble, Prometheus, Schering-Plough and Shire. KBG has received honoraria from and served as a consultant to Abbott Laboratories, Amgen, Centocor, Galderma, Pfizer, Merck and Lilly and has received grants from Abbott, Amgen, Centocor and Celgene. MJM and AL are employees of Abbott Laboratories and may hold stock or stock options.

Figures

Figure 1
Figure 1
Time to first serious infection, by indication. AS, ankylosing spondylitis; CD, Crohn's disease; JIA, juvenile idiopathic arthritis; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
Figure 2
Figure 2
Time to first malignancy, other than lymphoma or non-melanoma skin cancer (NMSC), by indication. AS, ankylosing spondylitis; CD, Crohn's disease; JIA, juvenile idiopathic arthritis; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
Figure 3
Figure 3
Standardised incidence rates (SIR, (95% CI)) for all malignancies excluding NMSC, lymphomas and NMSC for RA, AS, PsA, Ps and CD. No malignancies were observed for juvenile idiopathic arthritis. aAll malignancies other than NMSC. bBased on data from 14 160 patients. AS, ankylosing spondylitis; CD, Crohn's disease; NMSC, non-melanoma skin cancer; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
Figure 4
Figure 4
Standardised death rates (SMR, (95% CI)) for all indications, RA, AS, PsA, Ps and CD. No deaths occurred in juvenile idiopathic arthritis. aNo deaths occurred among female patients with AS. AS, ankylosing spondylitis; CD, Crohn's disease; Ps, psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.
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References

    1. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008;117:244–79 - PubMed
    1. Hochberg MC, Lebwohl MG, Plevy SE, et al. The benefit/risk profile of TNF-blocking agents: findings of a consensus panel. Semin Arthritis Rheum 2005;34:819–36 - PubMed
    1. Keystone EC. Does anti-tumor necrosis factor-α therapy affect risk of serious infection and cancer in patients with rheumatoid arthritis?: a review of long-term data. J Rheumatol 2011;38:1552–62 - PubMed
    1. Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006;54:692–701 - PubMed
    1. Dommasch ED, Abuabara K, Shin DB, et al. The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol 2011;64:1035–50 - PMC - PubMed

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