van Oosten BW, Barkhof F, Truyen L, et al
van Oosten BW, Barkhof F, Truyen L, et al. 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 benefitCrisk profile. Tumour TAS-116 necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohns disease (CD) and psoriasis. Anti-TNF therapies have proved effective in these diseases, either as monotherapy or in combination with other immunosuppressive therapies. All three commercially available TNF antagonists, adalimumab (Humira; Abbott Laboratories, Abbott Park, Illinois, USA), etanercept (Enbrel; Immunex, Thousand Oaks, California, USA) and infliximab (Remicade; Centocor, Inc, Malvern, TAS-116 Pennsylvania, USA), are indicated for RA, PsA, AS and psoriasis.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Adalimumab and infliximab are also indicated for CD; adalimumab and etanercept are indicated for JIA. 16 17 18 19 20 21 Based on the results of clinical trials,1 2 3 4 5 6 7 8 9 10 11 12 16 17 18 19 20 21 questions have arisen about the potential risk of serious infections, including tuberculosis, and malignancies with TNF antagonists.22 23 24 Other adverse events (AE) of interest that have been reported following TNF antagonist treatment include lupus-like syndromes, demyelinating disorders and congestive heart failure (CHF).25 26 27 28 29 Long-term data from an extensive number of patients with different immune-mediated inflammatory diseases can provide further insight into the safety of TNF blockade. Adalimumab, the first fully human monoclonal antibody targeted against TNF, was first administered to a study patient in 1997.30 We evaluated safety data from approximately 10 years of clinical trial experience with adalimumab in six diseases. Our primary objectives were to: (1) extend the results of the initial RA clinical trial safety analysis by Schiff infection, oesophageal candidiasis and candida sepsis. In CD, two cases (0.08/100 patient-years) of opportunistic infections that were SAE occurred, one case each of nocardiosis and coccidioidomycosis. Opportunistic infections were infrequently reported among patients with other immune-mediated inflammatory diseases: six cases in PsA; eight in AS; one in JIA and five in psoriasis. Nearly all reported events were oral candidiasis; none were SAE (table 2). No cases of progressive multifocal leukoencephalopathy have been reported in adalimumab clinical trials. Demyelinating disorders Few cases of demyelinating disorders were reported during adalimumab clinical trials (table 2). Thirteen cases were reported in RA studies: six cases of multiple sclerosis; two TAS-116 GuillainCBarr syndrome; two optic neuritis; two non-specific demyelination TAS-116 and one optic nerve disorder. Ten (0.05/100 patient-years) were SAE. One optic neuritis event (0.08/100 patient-years), also an SAE, was reported during AS trials. Three cases of optic neuritis and one case of multiple sclerosis were reported in CD studies. Three (0.13/100 patient-years) were SAE. TAS-116 No demyelinating disorders were observed in JIA, PsA and psoriasis trials. Lupus-like syndrome Lupus-like syndrome was infrequent among adalimumab-treated patients (table 2). Thirty-five events in the lupus-like syndrome category occurred during RA trials, only 12 (0.07/100 patient-years) were SAE: six cases of lupus-like syndrome; three systemic lupus erythematosus; two cutaneous lupus erythematosus and one antiphospholipid antibody syndrome. Six events were reported in CD trials. Only one case (0.04/100 patient-years) of lupus-like syndrome was an SAE. One patient in the psoriasis clinical development programme developed cutaneous lupus erythematosus, which was not considered an SAE by the investigator. No cases were reported in PsA, AS and JIA trials. Most patients with RA or CD who reported lupus-like syndrome SAE presented with cutaneous manifestations or serositis. NOV None had internal organ involvement (eg, nephritis). Adalimumab malignancy and mortality rates versus data from the general population Malignancies The risk of malignancy was not greater at any one point.