2 research outputs found
Exposure-Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results From Phase II and Phase III Induction and Maintenance Studies
Tofacitinib is an oral small molecule JAK inhibitor for the treatment of ulcerative colitis. Relationships between plasma tofacitinib concentration and efficacy were characterized using exposure-response (E-R) models, with demographic and disease covariates evaluated as potential predictors of efficacy. Data were from phase II and III (OCTAVE Induction 1 and 2) induction studies, and a phase III maintenance study (OCTAVE Sustain). Induction studies included 1,355 patients (tofacitinib 0.5, 3, 10, or 15Â mg b.i.d. or placebo). The maintenance study included 592 patients (tofacitinib 5 or 10Â mg b.i.d. or placebo). E-R models, including induction patients predicted placebo-adjusted remission rates of 6.4% and 12.7% at week 8 for tofacitinib 5 and 10Â mg b.i.d., respectively; corresponding rates in patients without prior tumor necrosis factor inhibitor (TNFi) failure were 12.8% and 20.4%. Estimates to achieve/maintain remission at week 52 of maintenance were 29% and 18% (tofacitinib 5Â mg b.i.d.), and 41% and 26% (tofacitinib 10Â mg b.i.d.), for patients in remission or not following induction, respectively. During maintenance, patients with prior TNFi failure had lower probability of remission on 5Â mg b.i.d. (24.9%) than 10Â mg b.i.d. (35.0%). Results indicated tofacitinib 10Â mg b.i.d. was an appropriate induction dose but suggested efficacy with 5Â mg b.i.d. in patients without prior TNFi failure. Tofacitinib 5Â mg b.i.d. was efficacious for maintenance, although patients with prior TNFi failure might see additional benefit on 10Â mg b.i.d. Per product labeling, recommended tofacitinib induction dose is 10Â mg b.i.d., then maintenance at 5Â mg b.i.d. For patients who lose response during maintenance, 10Â mg b.i.d. may be considered, limited to the shortest duration. Clinicaltrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01458574