relacionados con la calidad P300 Salud de los resultados de la vida hasta la semana 22 del estudio CERTIFI, un estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo Phase2b de ustekinumab en pacientes con enfermedad moderada a severamente activa de Crohn

Background: To examine the impact of ustekinumab (UST) on HRQoL in CD over the course of induction and maintenance, in the CERTIFI study. Methods: Patients with a CDAI score ≥220 and ≤450 who had previously failed or been intolerant of ≥1TNF antagonists were randomized to IV PBO or UST (1, 3, or 6 mg/kg) at wk0. At wk8, patients who received IV UST induction and were either responders (≥100 CDAI decrease) or non-responders at wk6, were re-randomized separately to SC maintenance with 90 mg UST or PBO at wks8 and 16, and assessed for maintenance efficacy at wk22. The IBDQ, assessing 4 dimensions of bowel symptoms, emotional function, systemic symptoms, and social function, was administered at wks0 (baseline), 6 and 22. Mean change from baseline in IBDQ and in each dimension of IBDQ, and the proportion of patients achieving a minimal clinically important difference (MCID) (≥16 point improvement from baseline in IBDQ), were assessed at wk6 and wk22. Results: Median age was 38yrs and 58.7% of patients were female (n = 526). In the induction phase, among the 500 patients analyzable for IBDQ, the combined patients randomized to IV UST had a baseline mean (SD) IBDQ score of 115.5 (28.64) vs 119.5 (26.69) for IV PBO. For the 1, 3, and 6 mg/kg IV UST doses, mean improvement from baseline in IBDQ at wk6 (19.9, 22.7, and 24.8, respectively) was statistically significant vs PBO (11.8) (p < 0.05). The proportion of patients with a MCID at wk6 was 33.1% on PBO vs 45.0% on IV UST 1 mg/kg (p = 0.057), 47.7% on 3 mg/kg (p = 0.018), and 54.7% among those randomized to 6 mg/kg (p < 0.001). Changes in IBDQ dimension scores from baseline to wk6 were each significantly improved in combined IV UST vs IV PBO patients (p < 0.05). Of the 145 responders to IV UST induction who were rerandomized in the maintenance phase, the mean (SD) IBDQ score at wk22 was 158.8 (38.58) among those who continued to receive SC UST vs 138.5 (39.71) of patients re-randomized to SC PBO (p < 0.001). The proportion of patients with a MCID was 68.1% (47/69) among those who continued to receive SC UST vs 44.9% (31/69) of patients re-randomized to SC PBO (p = 0.005). At wk22, mean IBDQ dimension scores in wk6 UST responders remained significantly higher with SC UST vs SC PBO maintenance (p < 0.05). Conclusions: In moderate-to-severe CD patients who failed previous TNF antagonist(s), IV UST induction significantly improved HRQOL vs PBO. During maintenance with SC UST, significant improvement in HRQOL in responders to induction was maintained through wk22.