Janssen's Stelara (Ustekinumab) Demonstrates Sustained Efficacy in Crohn’s Disease Over Five Years in IM-UNITI Long-Term Extension Study

October 13, 2020 News /Bio ValleyBIOON/ -- Johnson & Johnson (JNJ) recently at the 28th European Digestive Disease Week (UEG Week 2020) virtualMeetingThe latest and final 5-year data from the Phase 3 IM-UNITI open-label long-term extension (LTE) study of the anti-inflammatory drug Stelara (Chinese brand name: Xidano; generic name: ustekinumab, ustekinumab injection) were published. The results demonstrated that Stelara treatment maintained long-term remission for up to 5 years in patients with moderate-to-severe Crohn’s disease (CD).

IM-UNII was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study evaluating the efficacy and safety of Stelara maintenance therapy in adult patients with moderate-to-severe Crohn’s disease (CD). Patients who responded to a single intravenous infusion of Stelara in the UNITI-1 or UNITI-2 induction studies were randomized in a 1:1:1 ratio to receive subcutaneous (SC) Stelara 90 mg every 8 weeks (Q8W), every 12 weeks (Q12W), or placebo. A total of 1,281 patients were enrolled in the maintenance study. Among randomized patients who met the criteria for loss of response during Weeks 8–32, a one-time dose adjustment to 90 mg Q8W was permitted. All patients who completed Week 44 were eligible to enter the long-term extension (LTE) program, continuing their current treatment regimen through Week 252.

Key results showed that in the LTE study, among patients with moderately to severely active Crohn’s disease who were randomized to receive subcutaneous Stelara every 8 weeks (Q8W) and continued this dosing regimen in the LTE study, more than half maintained clinical response (57%) and clinical remission (55%) over 5 years of treatment. Among those patients in clinical remission, 93% were steroid-free.

Subgroup Analysis Table, in patients who have never received anti-TumorIn the subgroup of patients who had previously received tumor necrosis factor-alpha (TNF-α) biologics, 59% achieved clinical remission after 5 years of maintenance treatment with subcutaneous Stelara every 8 weeks (Q8W). Furthermore, in the subgroup of patients who had failed or were intolerant to TNF-α therapy, 44% achieved clinical remission after 5 years of maintenance treatment with subcutaneous Stelara Q8W. Among all patients (randomized and assigned) who entered the long-term extension (LTE) study, approximately half (51% [290/567]) completed the final dosing visit.

During the 5-year treatment period, the incidence rates (per 100 patient-years) of adverse events (AEs), serious adverse events (SAEs), and serious infections in the Q8W Stelara group were generally comparable to those in the placebo group. By Week 272, the rate of anti-Stelara antibodies remained low, at 5% among patients assigned to receive Stelara in the maintenance study who continued to receive the approved 90 mg subcutaneous every-8-weeks regimen in the long-term extension (LTE). No new safety signals were observed.。

Dr. William J. Sandborn, Professor of Medicine and Chief of Gastroenterology at the University of California, San Diego, who reported the study results, stated, “Crohn’s disease (CD) is one of the most debilitating inflammatory bowel diseases, disrupting the lives of millions of patients worldwide. The results of the IM-UNITI study demonstrate that patients can maintain efficacy for up to 5 years with Stelara maintenance therapy. Notably, among patients in clinical remission, the majority (more than 90%) treated with Stelara every 8 weeks (Q8W) remained steroid-free over the 5-year period.”

Stelara is the first biologic agent worldwide capable of simultaneously and selectively targeting IL-12 and IL-23. IL-12 and IL-23 are two naturally occurring cytokines believed to play a pivotal role in immune-mediated inflammatory diseases, including ulcerative colitis (UC), plaque psoriasis, psoriatic arthritis, and Crohn’s disease. Stelara inhibits these two pro-inflammatory cytokines by binding to the shared p40 subunit of IL-12 and IL-23, thereby blocking their interaction with the cell surface receptor IL-12β1.

Stelara was launched in September 2009, and its currently approved indications include the treatment of: (1) adolescent (≥6 years old) and adult patients with moderate-to-severe plaque psoriasis; (2) adult patients with active psoriatic arthritis; (3) adult patients with moderate-to-severe Crohn’s disease (CD); (4) adult patients with moderate-to-severe active ulcerative colitis (UC).

In China, Stelara® (Xidano®) was launched in June 2019. This biologic agent features an innovative dosing regimen—subcutaneous injection once every three months during the maintenance phase—and is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who have failed to respond to, have contraindications to, or are intolerant of other systemic therapies, such as cyclosporine, methotrexate (MTX), or PUVA (psoralen and ultraviolet A).

Stelara is Johnson & Johnson's entry intoAutoimmunityAs a core product in the field of immune-mediated diseases, this drug achieved sales of $6.361 billion in 2019. In January this year, an article titled “Top product forecasts for 2020” published in the prestigious international journal Nature pointed out that with the continuous expansion of indications, market growth, and increased penetration, Stelara’s sales were projected to reach $7.241 billion in 2020, ranking seventh among the “Top 10 Best-Selling Drugs Worldwide in 2020.” (Bioon.com)

Original Source: STELARA® (ustekinumab) Five-Year Results Presented from Long-term Extension Study of Clinical Response and Remission in Patients with Moderate to Severe Crohn's Disease