Randomised controlled trials session

In a round-up of randomised controlled studies in IBD at UEG Week 2019 included results from the maintenance phase of the UNIFI study in UC and a phase-3 study documenting the efficacy and safety of anti-IL23p19 monoclonal antibody mirikizumab in CD.

A subgroup analysis from the phase-2b U-ACHIEVE study shows that the oral selective JAK-1 inhibitor upadacitinib was effective as induction therapy in a population of patients with more severe and/or refractory UC who had had an inadequate response or list response to previous biologic therapy, or were intolerant to biologics (Bio-IR). Dr Remo Panaccione (University of Calgary, Canada), presented the results of the subgroup analysis which evaluated the primary and key secondary endpoints in the study in patients who were Bio-IR and non-Bio-IR, respectively. The four dose groups of upadacitinib (7.5mg, 15mg, 30mg and 45mg once daily) displayed a dose response relationship for the majority of the endpoints including clinical remission at Week 8, which was the primary endpoint. The clinical efficacy was consistently numerically higher in the non-Bio-IR subgroup. Upadacitinib was generally well tolerated with very few adverse events leading to treatment discontinuation.

Dr Panaccione also presented the Week 44 results from the phase-3, placebo-controlled UNIFI study of ustekinumab in patients with moderate to severe UC who had failed conventional or biologic therapy. During the maintenance phase patients received subcutaneous ustekinumab either once every eight weeks or once every 12 weeks or placebo for 44 weeks. Among patients who had achieved a clinical response eight weeks after receiving a single intravenous induction dose of ustekinumab, the rates of clinical and symptomatic remission and endoscopic improvement at Week 44 were similar in the two dose groups. In contrast, patients who failed to respond to the single induction dose or had a higher inflammatory burden were more likely to benefit from receiving subcutaneous ustekinumab once every eight weeks as maintenance therapy, suggesting that a number of clinical measures can be used for choosing maintenance therapy with ustekinumab in UC patients.

A retrospective multicentre study in France compared vedolizumab with infliximab after failed initial treatment with subcutaneous anti-TNF in UC. A total of 225 patients in 12 centres were included in the study, the results of which were presented by Dr Marianne Hupé (CHU de Bordeaux Hopital Haut-Leveque, Pessac Cedex, France). At Week 14, more patients treated with vedolizumab had achieved clinical remission, defined as a partial Mayo Score (pMS) of 1 or less. After adjustment for baseline factors, this difference was not statistically significant. Patients treated with vedolizumab were also numerically more likely to have a clinical response or achieve steroid-free remission. Over a median follow-up period of 115 weeks, patients on vedolizumab were significantly more likely to remain on treatment and be free of UC-related events such as hospitalisation or colectomy than those taking infliximab.

Professor Bruce Sands (Mount Sinai Hospital, New York, USA) presented the results of a phase-2, randomised, placebo-controlled study of mirikizumab in CD- Mirikizumab is a humanised monoclonal antibody against the p19 subunit of IL-23 which has been previously shown to be effective for treating UC and psoriasis. This 12-week study included a total of 191 patients who were randomised to one of three different doses of mirikizumab (200mg, 600mg or 1,000mg every four weeks) or placebo. At Week 12, patients in all three mirikizumab arms had significantly higher rates of endoscopic repsonse (primary endpoint) and endoscopic remission compared with patients in the placebo arm. Mirikizumab also resulted in significant and meaningful improvements in patient-reported outcomes and CDAI. The safety profile of mirikizumab was consistent with that seen in other indications. Mirikizumab is currently being evaluated in an ongoing phase-3 trial in CD which includes ustekinumab as an active comparator.