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27th September 2023
The use of risankizumab (brand name Skyrizi) in the treatment of adult patients with moderately to severely active Crohn‘s disease met the two primary endpoints in a head-to-head study compared to ustekinumab, its manufacturer AbbVie has announced.
While both risankizumab and ustekinumab are already approved for Crohn‘s disease and other conditions, their modes of action are different, with the former selectively blocking interleukin-23 (IL-23) signalling and the latter blocking both IL-12 and IL-23. The researchers therefore sought to determine if these differences affect treatment outcomes.
In the phase 3, multi-centre, randomised, head-to-head SEQUENCE study, the primary endpoint was non-inferiority for clinical remission at week 24 and superiority of endoscopic remission at week 48.
All participants had a confirmed diagnosis of Crohn‘s disease for at least three months and a Crohn‘s Disease Activity Index (CDAI) score of 220 to 450 at baseline. They were also considered to have moderate-to-severe disease based on an assessment of stool frequency, abdominal pain score, their Simple Endoscopy Score for Crohn‘s Disease (SES-CD), and a demonstrated intolerance or inadequate response to one or more anti-TNF therapies.
Participants assigned to risankizumab received a 600 mg intravenous induction at Weeks 0, 4 and 8 and 360 mg subcutaneous injection starting at week 12 and every eight weeks thereafter, through to week 48.
The results of the first primary endpoint, clinical remission (per CDAI, defined as CDAI <150) at week 24, met non-inferiority of risankizumab versus ustekinumab (non-inferiority margin of 10%). Remission rates were 59% in the risankizumab group and 40% in the ustekinumab group.
For the second primary endpoint of endoscopic remission (SES-CD ≤4 and at least a two-point reduction versus baseline and no sub-score greater than 1 in any individual component) at week 48, risankizumab provided a remission rate of 32% compared to 16% in the ustekinumab group (p < 0.0001).
In a commentary of these results, Dr Laurent Peyrin-Biroulet, director of the Infinity Institute, professor of gastroenterology and head of the inflammatory bowel disease group at the gastroenterology department, University Hospital of Nancy in France, said: ‘These results add to our growing body of evidence for Skyrizi in Crohn‘s disease. This study highlights the efficacy of Skyrizi compared to ustekinumab in helping eligible patients achieve clinical and endoscopic treatment goals and also reinforces the safety profile observed in previous studies.’
Full results from the SEQUENCE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.
20th July 2021
Psoriatic arthritis (PsA) is a chronic, immune-mediated disease which affects around 22% of those with psoriasis. PsA can present as a combination of axial and peripheral disease with signs including arthritis, enthesitis, dactylitis as well as skin and nail changes. The disease can be treated with non-steroidal anti-inflammatory drugs, synthetic disease-modifying anti-rheumatic drugs but over recent years, there has been an increase in the use of biologic agents. The rational for the use of biologics, arises from evidence implicating a pathological role for the interleukin (IL)-12, and IL23 and IL-17 pathways in the disease. Ustekinumab is an IL-12/23 inhibitor and has been shown to give rise to significant and sustained improvements in the signs and symptoms of PsA. Equally, there is evidence that tumour necrosis factor (TNF) inhibitors are also an effective therapeutic modality, preventing radiographically observed progression of joint destruction in PsA. Nevertheless, an important consideration when deciding to use a biologic agent is which agent is most appropriate. This decision-making is hampered given the absence of head-to-head trials comparing ustekinumab with TNF inhibitors. In trying to compare the relative efficacy of these two treatments, a team from the University of Vienna, Austria, turned to data from the PsABio study. This international, prospective, observational, cohort study, is designed to evaluate the persistence, effectiveness and tolerability of ustekinumab verses TNF inhibitors in patients with PsA. All participants are followed-up biannually for 3 years with an initial analysis of outcomes after 6 months. The outcomes used are the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) and Minimal Disease Activity (MDA) or Very Low Disease Activity (VLDA). DAPSA, MDA and VLDA, are considered to be the most useful measures for the assessment of patients with PsA and are based on assessments of several measures including joint tenderness, swelling, and self-reported pain with higher scores reflecting more severe disease. Remission of disease has been defined by a cut-off score of less than 4. Participants were enrolled at 92 sites across Europe and the initial choice of treatment was made at the discretion of the patient’s rheumatologist. Data were collected, from the patient’s medical records, at baseline and then every 6 months.
A total of 868 patients (426 using ustekinumab) were included in the analysis. The mean age of ustekinumab participants was 51.2 years (43% male) whereas the TNF inhibitor participants were significantly younger (mean age 48.5 years, 45.7% male). In addition, disease duration was longer for those using ustekinumab (7.5 vs 6.2 years). Baseline cDAPSA scores were similar (31 vs 29.8, ustekinumab vs TNF inhibitors) and the improvement after 6 months was also similar (-13.7 vs -14.5). Furthermore, cDAPSA remission occurred in 17.5% vs 21.9% (ustekinumab vs TNF inhibitors).
In their discussion the authors commented on how their data clearly shows how both agents had a similar impact on PsA disease activity after only 6 months. They concluded by indicating that future publications will include a longer-term evaluation of the current data.
Smolen JS et al. Effectiveness of IL-12/23 inhibition (ustekinumab) versus tumour necrosis factor inhibition in psoriatic arthritis: observational PsABio study results. Ann Rheum Dis 2021