Adalimumab, etanercept, infliximab, and the risk of tuberculosis: data from clinical trials, national registries, and postmarketing surveillance.
This review evaluates the risk of tuberculosis (TB), adherence with recommendations for TB prevention, and host-related risk in patients with rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis receiving infliximab (IFX), adalimumab (ADA), and etanercept (ETN) through an analysis of phase III randomized controlled trials (RCT), postmarketing surveillance, and national registries. Ten (0.21%) TB cases occurred among 4590 patients in 16 RCT of IFX, 9 (0.12%) among 7009 patients in 21 RCT of ADA, and 4 (0.05%) among 7741 patients in 26 RCT of ETN. Overall, 19/23 (83%) TB cases occurred in patients with RA. Data from national registries and postmarketing surveillance showed an increased risk of TB in patients receiving any of the 3 anti-tumor necrosis factor (TNF) drugs, with a 3-4 times higher risk associated with IFX and ADA than with ETN. Deviations from recommended TB prevention procedures were observed in up to 80% of patients, and most registries did not include data on host-related risk factors for TB. TB occurrence was reduced in recent RCT but not in real-life practice. TB risk was lower for ETN than for monoclonal antibody anti-TNF agents. More complete data collection, including host-related TB risk factors, is advisable to avoid biased results.
Address correspondence to Dr. Cantini, Rheumatology Division, Piazza Ospedale 1, 59100 Prato, Italy. E-mail: fbrzcantini@gmail.com.
Fabrizio
F
Cantini
Laura
L
Niccoli
Delia
D
Goletti
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D000069285:Infliximab; D011358:Product Surveillance, Postmarketing; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012042:Registries; D012216:Rheumatic Diseases / Q000188:drug therapy; D012306:Risk; D014376:Tuberculosis / Q000209:etiology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
ADALIMUMAB; CLINICAL TRIALS; ETANERCEPT; INFLIXIMAB; REGISTRIES; TUBERCULOSIS