Vedolizumab Efficacy, Safety, and Pharmacokinetics with Reduced Frequency of Dosing From Every 4 Weeks to Every 8 Weeks in Patients with Crohn's Disease or Ulcerative Colitis.

BACKGROUND AND AIMS: Vedolizumab was shown to be safe and effective for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI long-term safety (LTS) study. The vedolizumab Extended Access Program (XAP) provides patients with continued treatment. The XAP pharmacokinetics (PK) substudy investigated vedolizumab efficacy, safety, and PK. METHODS: Vedolizumab dosing frequency was reduced from every 4 weeks (Q4W) to every 8 weeks (Q8W) at XAP enrollment and patients were followed for 56 weeks. Outcomes included efficacy, loss of clinical benefit and re-escalation to Q4W dosing, vedolizumab PK, immunogenicity, and adverse events. RESULTS: Among 167 enrolled patients (CD=88, UC=79), 80 (91%) with CD and 73 (92%) with UC completed 56 weeks; 76 (86%) and 71 (90%) with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and 2 with UC resumed Q4W dosing (3 with CD regained clinical response). Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 microg/mL at enrollment and 10.4 microg/mL at Week 56; concentrations were 42.4 microg/mL and 13.3 microg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. CONCLUSIONS: In the XAP-PK substudy, adherence to Q8W dosing was high with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.