NEW YORK (Reuters Health) Dec 02 - Ten years of clinical trials have shown adalimumab to be safe for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, and juvenile idiopathic arthritis, according to a report in the December Annals of the Rheumatic Diseases.
"TNF blocking agents - in this case represented by adalimumab - are generally safe, especially...where no severe comorbid conditions exist and concomitant therapy does not include steroids," Dr. Gerd R. Burmester, from Free University and Humboldt University of Berlin, told Reuters Health by email.
Dr. Burmester and colleagues evaluated safety data from the earliest clinical trials of adalimumab in 1997 through 2007. Overall, they analyzed 36 global clinical trials involving 19,041 patients with these six diseases.
The most serious adverse events were infections, the authors report, with rates (depending on year) ranging from 4.6 to 5.1 infections per 100 patient-years.
Serious infection rates were highest in rheumatoid arthritis (most commonly pneumonia) and Crohn's disease (most commonly abscess).
Other serious adverse events included tuberculosis (0.22 to 0.29/100 patient-years), lymphomas (0.10 to 0.21/100 patient-years), demyelinating disease (0.05 to 0.08/100 patient-years), and lupus-like syndrome (0.05 to 0.10/100 patient-years).
Among all diseases treated with adalimumab and in rheumatoid arthritis trials alone, no malignancy other than lymphoma and non-melanoma skin cancer had significantly greater incidence compared with the general population.
Standardized mortality rates for patients treated with adalimumab across these 6 indications were all less than what would be expected for the general population, the researchers note.
"Further studies are necessary to analyze if this is due to a 'healthy cohort effect' (patients included in clinical trials usually have fewer comorbid conditions and are very closely monitored/treated early) or to a less inflammatory state also influencing cardiovascular inflammation or to both effects combined," Dr. Burmester said.
"Patients should be closely monitored for infections taking into account symptoms such as cough, fever, and constitutional symptoms," the researcher continued. "Prior to therapy, latent tuberculosis should be assessed by a thorough patient history, chest x-ray (recommended in Germany), possibly a PPD skin test, and most recently in-vitro gamma-interferon release assays."
He added, "In case of latent tuberculosis, preventive therapy should start prior to the initiation of a TNF blocking agent."
Ann Rheum Dis 2009;68:1863-1869.