Lutikizumab Improves HS Pain, Flares in Phase 3 INTREPID Study

Lutikizumab, an investigational antagonist of both interleukin 1α (IL-1α) and IL-1β, outperformed placebo on the stringent Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) end point at Week 16 in adults and adolescents with moderate to severe hidradenitis suppurativa (HS), according to topline phase 3 INTREPID results announced by AbbVie.¹

The trial also met all 8 of its ranked secondary end points, including measures of skin pain and flare frequency. AbbVie characterized INTREPID as the first phase 3 HS trial enrolling both adults and adolescents to reach statistical significance with HiSCR75 as its primary end point. The company noted IL-1α and IL-1β are both elevated in HS lesions, the biological basis for testing a dual-variable-domain antibody against the 2 cytokines.¹

How Was the INTREPID Trial Designed?

INTREPID (NCT06468228) is a multicenter, randomized, double-blind, placebo-controlled study enrolling 1400 patients across North America, South America, Europe, and Asia. Subjects involved were assigned 1:1 to subcutaneous lutikizumab or placebo for a 16-week placebo-controlled period, followed by blinded lutikizumab from weeks 16 to 52 and a 156-week open-label extension.¹˒²

HiSCR75 required a reduction of at least 75% in combined abscess and inflammatory nodule (AN) count without any rise in abscesses or draining tunnels.¹

What Efficacy Findings Were Seen with Lutikizumab Use at Week 16?

HiSCR75 response at Week 16 reached 31.4% with lutikizumab versus 23.4% with placebo (P ≤ .001).¹

Pain relief emerged early. At the 8-week mark, a reduction of at least 3 points on the HS-related skin pain Numeric Rating Scale (NRS3) occurred in 26.2% of the lutikizumab group compared with 15.0% of the placebo group, with separation noted as soon as week 1. A reduction of at least 30% and 2 units (NRS30) was achieved by 36.0% versus 22.8% (P < .0001 for both).¹

Fewer lutikizumab recipients experienced a flare, defined as an AN count increase of at least 25% and at least 2 lesions, during the first 16 weeks (18.4% vs 28.1%; P < .0001). Dermatology Life Quality Index and HS Impact Assessment scores also improved more with lutikizumab (P < .0001 for each), and IL-17A and IL-17F levels declined.¹

What Safety Findings Were Reported?

Overall adverse event rates were nearly identical between lutikizumab and placebo (53.4% vs 53.7%), as were rates of serious adverse events (3.0% vs 2.9%) and discontinuations due to adverse events (1.7% vs 1.9%). AbbVie reported no new safety signals compared with earlier studies.¹

Nasopharyngitis, upper respiratory tract infection, headache, fatigue, and injection-site reactions each occurred in at least 3% of lutikizumab-treated patients, with only injection-site reactions occurring more often than with placebo. Oral candidiasis rates were low in both arms (0.3% vs 0.4%), and no suicidal ideation was reported.¹ No deaths occurred among lutikizumab recipients, while 1 death was reported in the placebo group.

What Comes Next for Lutikizumab in HS?

Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, said many patients with HS continue to experience pain and flares on current therapies. She highlighted HiSCR75 as a demanding response threshold and noted these are the first phase 3 data on dual IL-1α and IL-1β blockade in the disease. Kimball is a consultant for AbbVie.¹

Results from a 36-week blinded extension are expected in 2027, with AbbVie planning regulatory submissions in the second half of 2027. Full data will be presented at an upcoming medical meeting.¹

AbbVie also plans to launch an HS platform study evaluating lutikizumab with ABBV-295, a long-acting amylin analog, and potentially ABBV-701, an anti-TL1A antibody. Lutikizumab is not approved by any regulatory authority.¹

Editor’s Note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. AbbVie announces topline results from the phase 3 INTREPID trial showing lutikizumab significantly improved signs and symptoms of disease in patients with hidradenitis suppurativa. News release. AbbVie. October 22, 2026. Accessed October 22, 2026. https://news.abbvie.com/2026-10-22-AbbVie-Announces-Topline-Results-from-the-Phase-3-INTREPID-Trial-Showing-Lutikizumab-Significantly-Improved-Signs-and-Symptoms-of-Disease-in-Patients-with-Hidradenitis-Suppurativa.

2. A study to assess disease activity and safety of lutikizumab in adult and adolescent participants with moderate to severe hidradenitis suppurativa (INTREPID). ClinicalTrials.gov identifier: NCT06468228. Accessed October 22, 2026. https://clinicaltrials.gov/study/NCT06468228.