Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial

Abstract

Background and aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomised, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy.

Methods: Patients had received tofacitinib 10 mg BID for ≥ 2 consecutive years and been in stable remission for ≥ 6 months before enrolment. The primary endpoint was modified Mayo score remission at Month 6. Safety was assessed up to February 20, 2020 [data cut-off].

Results: In all, 140 patients were randomised [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at Month 6 (adjusted difference 12.9%; 95% confidence interval [CI] 0.5-25.0). Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; -3.0-22.6, and 21.1%; -6.1-48.2, respectively], and in patients without versus with prior tumour necrosis factor inhibitor [TNFi] failure [9.5%; -6.6-25.6, and 17.4%; -1.6-36.3, respectively]. Adverse events [AE] and serious AE rates were similar across treatment groups; no deaths were reported.

Conclusions: Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6 months; a longer duration of follow-up during RIVETING will further characterise the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.

Keywords: Dose adjustment; maintenance; tofacitinib.

Graphical Abstract

Figure 1.

Patient disposition up to Month 6 of the RIVETING trial. AE, adverse event; BID, twice daily; N, number of patients in the analysis population; n, number of patients that withdrew from trial; UC, ulcerative colitis. ^aPatients who discontinued due to an AE of ‘colitis ulcerative’ [worsening UC] were categorised as lack of efficacy.

Figure 2.

Efficacy endpoints at Month 6 by dose group [FAS, non-responder^a]. [A] Proportion of patients in modified Mayo score remission [primary endpoint; defined as an endoscopic subscore of ≤ 1, a stool frequency subscore of ≤ 1, and a rectal bleeding subscore of 0] at Month 6. [B–F] Proportion of patients for secondary efficacy endpoints at Month 6: remission [defined as a total Mayo score of ≤ 2 with no individual subscore >1, and a rectal bleeding subscore of 0]; endoscopic improvement [defined as an endoscopic subscore of 0 or 1]; clinical response based on total Mayo score [defined as a decrease from induction study baseline total Mayo score of ≥ 3 points and 30%, plus a decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1]; remission based on modified partial Mayo score [defined as a stool frequency subscore of ≤ 1 and a rectal bleeding subscore of 0]; remission based on partial Mayo score [defined as a partial Mayo score of ≤ 2, with no individual subscore ≥ 1 and a rectal bleeding subscore of 0]. BID, twice daily; CI, confidence interval; FAS, full analysis set; N, number of patients in the treatment group. ^aPatients with missing scores were treated as non-responders. Patients in the tofacitinib 5 mg BID group with dose escalation were treated as non-responders for visits after dose escalation. ^bDifferences are weighted difference based on the Cochran‐Mantel‐Haenszel weight method and 95% CI using the Newcombe method, stratified by baseline endoscopic subscore [0 or 1].

Figure 3.

Kaplan‐Meier plot of time to loss of remission [flare] based on modified Mayo score [FAS]. BID, twice daily; FAS, full analysis set; N, number of patients in the analysis set.