Area Editoriale
Importante lezione di questo studio danese: in una piccola porzione di pazienti l'efficacia del farmaco viene mantenuta nonostante la positività degli anticorpi anti-infliximab (nonostante lo studio in vitro confermi la loro fubnzionalità biologica) e nel 60 per cento di questi gli anticorpi si negativizzano entro 8-10 mesi. Un altro dato inatteso è la persistenza degli anticorpi, nei pazienti con perdita di risposta, non solo in caso di prosecuzione della terapia (come prevedibile) ma anche per lunghi periodi dopo la sua sospensione (oltre l'anno nel 70 per cento e fino a tre anni nel 25 per cento circa dei pazienti)
Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease.Steenholdt C, Al-khalaf M, Brynskov J, Bendtzen K, Thomsen OØ, Ainsworth MA. Inflamm Bowel Dis. 2012;18:2209-17
BACKGROUND: The aim of the study was to investigate variations in anti-infliximab (IFX) antibody (Ab) levels and clinical implications thereof in patients with inflammatory bowel disease (IBD). METHODS: A retrospective, explorative, single-center study of patients with IBD who developed anti-IFX Ab and in whom anti-IFX Ab were reassessed. RESULTS: IFX was administered to 316 patients; anti-IFX Ab was determined in 180 patients and detected in 83 (46%). During ongoing IFX maintenance therapy,
anti-IFX Ab disappeared at later reassessment in two-thirds of patients with
clinical response after median 4 (3-5) infusions. In contrast, anti-IFX Ab persisted in all patients without clinical response. Anti-IFX Ab appeared
pharmacologically active, as IFX levels were high when anti-IFX Ab isappeared (median 3.7 μg/mL, interquartile range [IQR] 2.8-5.5), while undetectable or low when anti-IFX Ab persisted (median 0 μg/mL, IQR 0-0). In 56 patients, anti-IFX Ab were assessed after IFX discontinuation. The proportion of patients with anti-IFX Ab gradually declined over time, with a few patients having anti-IFX Ab up to about 4 years after initial assessment. No variables were associated with anti-IFX Ab disappearance in multivariate analysis. CONCLUSIONS: Discontinuation of IFX is advisable in patients with inadequate response and repeat positive anti-IFX Ab measurements. Anti-IFX Ab can persist for years after discontinuation, which could impact efficacy and safety at retreatment. Continued IFX treatment may, however, be considered in patients with clinical response and a single positive anti-IFX Ab measurement, as anti-IFX Ab disappears in two-thirds of these during continued treatment.