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OP014 Histological remission is predictive of improved clinical outcomes in patients with ulcerative colitis: results from the TOUCHSTONE open-label extension

Sandborn W.1, Feagan B.*2, D'Haens G.3, Levesque B.2, Pai R.4, Hanauer S.5, Wolf D.6, Vermeire S.7, Ghosh S.8, Li C.9, Penenberg D.9, Aranda R.9, Olson A.9

1University of California San Diego, San Diego, United States 2Robarts Research, London, Canada 3Academic Medical Center, Amsterdam, Netherlands 4Mayo Clinic, Department of Laboratory Medicine and Pathology, Scottsdale, United States 5Feinberg School of Medicine, Chicago, United States 6Atlanta Gastroenterology Associates, Atlanta, United States 7University of Leuven, Leuven, Belgium 8University of Calgary, Calgary, Canada 9Receptos, a wholly owned subsidiary of Celgene, San Diego, United States

Background

Histological remission (HR) has been reported as a positive prognostic indicator of clinical activity in ulcerative colitis (UC). The TOUCHSTONE open-label extension (OLE) is an opportunity to examine the impact of histologic remission on UC activity during a long-term evaluation of efficacy and safety of ozanimod 1 mg. TOUCHSTONE was a randomized, double-blind, placebo-controlled phase 2 trial designed to assess the efficacy and safety of ozanimod 0.5 mg and 1 mg versus placebo during induction and maintenance in patients with moderate to severe UC [1], and established that ozanimod induced and maintained clinical response, clinical remission (CR), endoscopic mucosal healing, and HR through weeks 8 and 32.

Methods

A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1 mg, or placebo in TOUCHSTONE. Of the initial 197 patients randomized, 170 (86%) entered OLE and received daily ozanimod 1 mg, and 131 (77%) and 105 (62%) completed assessments at weeks 44 and 80. In this analysis, HR was defined as a Geboes score <2 and CR was defined as rectal bleeding score =0 and stool frequency score ≤1.

Results

Of the patients who entered OLE, 27% showed histologic remission at the time of OLE entry and 34% were in CR. Clinical remission increased to 62% at OLE week 32, with 62%, and 55% in CR at OLE weeks 44 and 80. At OLE weeks 44 and 80, CR was seen in 83% and 80% of those in HR at OLE entry compared to 55% and 46% of those not in HR at OLE entry.

The proportion of patients in CR increased throughout OLE while receiving 1 mg of ozanimod, regardless of prior treatment in the TOUCHSTONE study or HR status at OLE entry. The highest rates of CR were seen in patients in HR at OLE entry who had received ozanimod for 32 weeks prior to OLE entry, with CR rates at OLE weeks 4 and 8, with over 90% in CR. The lowest CR rates were seen in patients naïve to ozanimod and not in HR at OLE entry, with CR increasing from 13% at entry to 50% at OLE week 8, reaching a peak of 56% at OLE week 32. Overall, treatment with ozanimod for 32 to 36 weeks resulted in CR in 80% of patients.

Most common adverse events seen in OLE were UC flare, back pain, URTI, anemia, and nasopharyngitis. Transient asymptomatic elevations in ALT or AST >3× ULN were seen in 3% of patients.

Conclusion

Histological remission is predictive of CR in patients with UC receiving ozanimod 1 mg in OLE. All patients, whether naïve to or having received ozanimod in TOUCHSTONE, showed additional improvements in CR upon continued treatment with ozanimod 1 mg in OLE. Patients naïve to ozanimod had a rapid improvement in CR over the first 8 weeks of treatment with ozanimod 1 mg in OLE.

References:

[1] Sandborn WJ, Feagan BG, Wolf DC, et al. (2016), Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med, 1754–62