Efficacy and Safety of Tofacitinib Retreatment for Ulcerative Colitis after Treatment Interruption: An Update of Results from the OCTAVE Clinical Trials

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Patients (pts) may need to temporarily suspend tofacitinib treatment for several reasons, such as adverse events (AEs), pregnancy or surgery; thus, it is key to assess the efficacy/safety of retreatment after treatment interruption.

METHODS:

We provide an update (1) of tofacitinib retreatment efficacy and safety data after treatment interruption in the ongoing, open-label, long-term extension (OLE) study (NCT01470612; data as of May 2019, database not locked). We analyzed pts in the OLE study who had a clinical response after 8 wks of tofacitinib 10 mg twice daily (BID) in OCTAVE Induction 1&2 (NCT01465763; NCT01458951) then received placebo in OCTAVE Sustain (NCT01458574) and had treatment failure after Wk8 up to Wk52 and subsequently received tofacitinib 10 mg BID in the OLE study. Treatment failure was defined as a $ 3-point increase from OCTAVE Sustain baseline total Mayo score plus a $ 1-point increase in rectal bleeding subscore and endoscopic subscore (ES) and an absolute ES $ 2 points after $ 8 wks' treatment. We evaluated efficacy up to Month (Mo) 36 of the OLE study and AEs throughout the study.

RESULTS:

Of 917 pts treated for $ 2 mo in the OLE study, 100 entered the study with a clinical response to tofacitinib 10 mg BID in OCTAVE Induction 1 or 2 followed by treatment failure on placebo during OCTAVE Sustain; median time to treatment failure was 135 days. After receiving tofacitinib 10 mg BID in the OLE study, clinical response was recaptured at Mo2 in 74.3% (non-responder imputation and last observation carried forward [NRI-LOCF]) and 85.2% of pts (observed data; Table 1). At Mo 12, 24 and 36, 43.6%, 40.6% and 37.0% (NRI-LOCF) and 62.0%, 69.5% and 72.0% (observed data) of pts were in remission, respectively. In pts with prior TNFi failure, 80.4% had a clinical response at Mo 2 and 47.8%, 37.0% and 28.3% were in remission at Mo 12, 24 and 36 (NRI-LOCF), respectively. Corresponding observed data were 92.5%, 66.7%, 70.8% and 63.2%, respectively. Incidence rates for AEs are reported (Table 1).

CONCLUSION:

In this post hoc analysis, in pts with prior response to tofacitinib induction, retreatment with 10 mg BID after 8-52 wks' treatment interruption was efficacious and well-tolerated, with clinical response recaptured in the majority of pts by Mo 2 and in half of pts at Mo 36. The safety profile was generally consistent with that in the overall study population.