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Stelara effective for induction, maintenance of UC regardless of biologic history
SAN DIEGO — Stelara was effective for the induction and maintenance treatment of patients with moderate-to-severe ulcerative colitis whether or not they previously failed biologic therapy, according to data from the UNIFI study presented at Digestive Disease Week.
“Ustekinumab [Stelara, Janssen] is an IL-12/23 blocker that’s approved for Crohn’s disease, and ... is also effective in induction and maintenance of clinical remission in patients with moderate-to-severe ulcerative colitis,” Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, said in his presentation. “But here we are looking at two distinct populations who came into this study.”
In the UNIFI trial, researchers randomly assigned patients to a baseline intravenous induction dose of ustekinumab (130 mg or weight-range doses of about 6 mg/kg) or placebo. Responders entered into maintenance therapy and received either 90 mg of ustekinumab (every 12 weeks or every 8 weeks) or placebo.
The trial included an analysis of the drug’s efficacy in patients who previously failed biologic treatment (51.1% of randomized patients), of which 98% had failed at least one anti-TNF, and 32.6% failed both anti-TNF and Entyvio (vedolizumab, Takeda).
During the induction phase of the trial, both doses of ustekinumab were superior to placebo regarding clinical remission in patients who were either biologic failures (BF; P < .001 for both doses) or non-biologic failures (NBF; P < .05 for both doses).
In the maintenance phase in both BF and NBF patients, the proportion of patients who achieved clinical remission was greater for both the every 8 weeks and every 12 weeks ustekinumab groups compared with placebo (BF P < .001, P = .044, respectively; NBF P = .024, P = .020).
Additionally, a greater proportion of NBF and BF patients in the ustekinumab every 8 weeks and every 12 weeks groups achieved each secondary endpoint of maintenance (clinical response, endoscopic healing, corticosteroid-free remission and clinical remission in baseline remitters) compared with the placebo groups.
“Ustekinumab was effective for induction and maintenance treatment of moderately-to-severely active UC as assessed by clinical response, clinical remission, endoscopic healing and steroid-free remission,” Sands concluded. “This effectiveness was also observed in patients with a history of biologic therapy failure which included both TNF antagonists, and as well as patients who had experienced and failed both anti-TNF and vedolizumab and patients without a history of biologic therapy failure.” – by Alex Young
Reference:
Sands BE, et al. Abstract 833. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.
Disclosures: Sands reports financial support for research from AbbVie, Allergan, Arena, Boeringher-Ingelheim, Celgene, Ferring, Gilead, Janssen, Lilly, Otsuka, Pfizer, Protagonist, Rheos Medicines, Synergy, Takeda, Theravance Biopharma R&D and TiGenix. Please see the study abstract for all other authors’ relevant financial disclosures.
Perspective
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Stelara (ustekinumab, Janssen) has been approved for the treatment of Crohn’s disease and it appears very safe and effective in the setting of Crohn’s disease.
What we have learned in Crohn’s and with every other secondary agent, whether it’s a secondary biologic or whether it’s a JAK inhibitor, is that patients who were naive to TNF therapy do better overall than the patients who had previously been exposed, whether or not they lost response or didn’t respond to TNF inhibitors.
This emphasizes that our first drug that we used for moderate-to-severe Crohn’s or ulcerative colitis is going to have the best opportunity to achieve benefit. It emphasizes to me that we need to use these safe and effective therapies earlier in the setting, particularly in Crohn’s disease because once patients start failing one drug or another, while there still is a benefit compared with placebo, the overall benefits are about half of that were patients who would never receive prior biologic therapy.
Now we see ustekinumab tested in ulcerative colitis. We have seen that it has benefits in inducing remission and in ulcerative colitis, endoscopy is part of the remission criteria. We know it also leads to improvement in the mucosa and as we saw in the Crohn’s disease studies with Stelara, the safety profile looks very good with no strong signals for infection. Although patients are treated with other concomitant medications, including steroids or other immunosuppressants, we always do see some infections. But serious infections do not appear to be greater with ustekinumab therapy than patients treated with placebo and other concomitant medicines.