Early and significant effects with upadacitinib induction treatment

A sub-analysis of the 16-week CELEST data evaluated the onset of achieving clinical response and remission with upadacitinib, an oral Janus kinase (JAK)1 inhibitor [10]. The patient group had moderate-to-severe active CD.

With upadacitinib 6, 12, and 24 mg BID, relatively more patients achieved modified clinical remission already at week 4 compared with placebo (P≤0.05 for each). Over time, this clinical measure was sustained in patients receiving the upadacitinib 24 mg BID induction dose for up to 16 weeks. Patients (n=220) were randomised double-blindly to placebo or immediate release upadacitinib 3, 6, 12, 24 mg BID, or 24 mg once daily for 16 weeks. Admission criteria were CDAI 220-450, average daily liquid/very soft stool frequency ≥2.5 or daily abdominal pain score ≥2.0, and SES-CD ≥6 (or ≥4 for those with isolated ileal disease). The mean age was 40.7 years, CDAI 302.8, and mean CD duration was 13.2 years.

Patients were randomised at baseline for follow-up ileocolonoscopy at either week 12 or 16. Overall, patients receiving upadacitinib achieved modified clinical remission (daily stool frequency ≤2.8 and abdominal pain score ≤1.0, both not worse than baseline) by week 4. Enhanced clinical response (stool frequency or abdominal pain score reduction from baseline ≥60% or ≥35%) was achieved with upadacitinib at week 8 compared with placebo. Both clinical endpoints were sustained in all dose groups for up to 16 weeks with variable statistical significance (likely due to small sample size). Mean CRP levels were significantly decreased in all upadacitinib dose groups at week 2. They were sustained for up to 16 weeks in the 12 and 24 mg BID and 24 mg once daily arms. Mean FCP decreased significantly from baseline with upadacitinib at 12 and 24 mg BID at week 4, and 24 mg BID at week 16.

In conclusion, early and significant effects of upadacitinib on clinical parameters were demonstrated in a refractory patient population with active CD. The effects are concurrent with a rapid and sustainable decrease in the markers CRP and FCP.