DAY 3: Efficacy and Safety of Biologics Targeting IL-12 and IL-23 in Inflammatory Bowel Disease

Jessica R. Allegretti, MD, MPH, FACG, from Brigham and Women’s Hospital and Harvard Medical School, presented week 48 efficacy and safety results from the phase 3 ASTRO study of subcutaneous guselkumab induction and maintenance therapy for ulcerative colitis (UC). Patients with moderate to severe UC (Mayo score 3) and who were naïve or had inadequate response or intolerance to advanced therapies were randomized to placebo (n=139), subcutaneous guselkumab 400 mg then 100 mg every 8 weeks (q8w; n=139), or subcutaneous guselkumab 400 mg then 200 mg every 4 weeks (q4w; n=140). The three groups had similar demographics and more than 55% had severe disease, 40% were experienced with advanced IBD therapies, and 15-20% were JAK inhibitor experienced. More patients discontinued from the placebo arm than the treatment arms, and there were 2 deaths not related to treatment. At week 48, 36.7% of patients in the q8w and 42.9% in the q4w arms achieved the primary endpoint of clinical remission, compared to 7.2% in the placebo group. A higher response was seen in patients naïve to advanced therapies. Similar week 48 improvements were seen across the two doses, regardless of advanced therapy experience, for endoscopic improvement, endoscopic remission, histologic improvement, and histologic-endoscopic mucosal improvement (HEMI) and remission. There were no new safety signals, and only 1.75% of patients had injection site reactions. As both doses had similar efficacy, the decision to use guselkumab q4w vs. q8w maintenance dosing would be based on provider and patient preference; for example, q4w dosing might be appropriate for more refractory disease.

Anita Afzali, MD, MPH, MHCM, FACG, from the University of Cincinnati College of Medicine, presented the results of a prespecified subgroup analysis of the GALAXI phase 3 studies of IV guselkumab induction followed by subcutaneous guselkumab maintenance with either 200 mg q4w (n=286) or 100 mg q8w (n=296) dosing in patients with moderate to severely active Crohn’s disease (CD). Clinical remission and endoscopic response at week 48 were determined for subgroups with CD activity index lower or higher 300 at baseline, SES-CD score higher or lower than 12, CRP higher or lower than 5 mg/L, and with or without endoscopic response at the end of induction at 12 weeks. Outcomes were better with subcutaneous guselkumab 200 mg q4w maintenance dosing for patients with high clinical or endoscopic disease severity at baseline, high inflammatory burden after induction, and who did not achieve endoscopic response after induction. Outcomes in patients with lower measures of disease severity were similar between the two maintenance doses.

Dr. Anfali also reported on the efficacy and safety of subcutaneous guselkumab used as rescue therapy in patients with moderately to severely active CD and inadequate response to ustekinumab from the GALAXI trials and long-term extension study. In the long-term extension, patients who did not respond to ustekinumab maintenance could be switched to subcutaneous guselkumab maintenance 200 mg q4w without induction. The analysis included 75 patients and 60% had a history of inadequate response to biologic therapy. Two-thirds of patients switched to guselkumab by week 60. Clinical response and remission 16 weeks after the treatment switch were similar in those who switched from ustekinumab versus those who had originally been randomized to guselkumab induction and maintenance. SES-CD scores at 1 year and endoscopic outcomes at week 96 were also the same between those who started on guselkumab versus those who switched to guselkumab. Event rates were similar to the known safety profiles. Two adverse events led to discontinuation: prostate cancer and bowel hemorrhage.

Additional posters of interest:

A multi-center longitudinal cohort study of 405 patients with UC found that upadacitinib achieved clinical remission of 80.6% at 1 year, with 1 cardiovascular event (transient ischemic attack) and 5 cases of herpes zoster infection. (P5325)

A real-world retrospective study found that ustekinumab maintenance dose escalation from every 6 weeks to every 4 weeks was associated with a significantly longer duration of therapy and higher rates of steroid-free remission in patients with CD or UC. (P3267)

A retrospective cohort study of response to risankizumab maintenance dose escalation to 360 mg every 4 or 6 weeks in patients with CD reported improved clinical response in 46% of patients, with improvements in CRP, ESR, and disease activity indices. (P1039)

Extended induction with mirikizumab in patients with UC in the LUCENT-3 open-label study found high rates of response that were sustained out to 4 years, with no new safety concerns. (P3190)
The GALAXI 2 & 3 and GRAVITI studies demonstrated 2-year efficacy and safety of subcutaneous guselkumab maintenance in patients with CD, with similar results with either guselkumab IV or subcutaneous induction. (P1066)

The QUASAR long-term extension study revealed maintenance of endoscopic and histologic efficacy with subcutaneous guselkumab at 92 weeks in patients with UC (P3189).
In the GRAVITI phase 3 trial in CD, subcutaneous guselkumab induction and maintenance achieved greater rates of histologic and histologic-endoscopic response and remission compared to placebo. (P3192)

Among patients with highly severe CD in the GALAXI and GRAVITI studies, induction with intravenous or subcutaneous guselkumab was similarly effective for improving clinical and endoscopic response and remission at week 12 (P3193).