Inhibitors in previously treated patients: a review of the literature.

Previously treated patients are the first patients to receive novel factor VIII products during clinical investigations under the rationale that a product with increased antigenicity is more likely to be detected in this population because of a low baseline risk of inhibitor formation compared with previously untreated patients. As clinical investigations of factor products are not typically randomized comparisons, the rate of new inhibitor formation in a clinical trial is compared with the expected rates based on prior reports. The published experience of inhibitors in previously treated patients (PTPs) informs the number of new inhibitors per cohort that are acceptable in a clinical trial. However, a single acceptable limit of new inhibitors fails to recognize the heterogeneity of inhibitors and their variable impact on clinical care. This review will discuss the published literature on epidemiology and clinical characteristics of inhibitors and possible risk factors for formation in PTPs.