TRANQUILITYHot Line 2Prevention
Pacibekitug for Inflammation Reduction in Chronic Kidney Disease at High Cardiovascular Risk
Monthly and quarterly pacibekitug in patients with chronic kidney disease at high cardiovascular risk
Presenting authorDeepak BhattInterventional / Structural Cardiology · Clinical Research InstituteDeepak L. Bhatt, MD, MPH, MBA, is the Director of the Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai. He is an American interventional cardiologist and researcher known for clinical trials in cardiovascular prevention and intervention. He previously served as Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School.
Key result
Pacibekitug significantly reduced hs-CRP compared to placebo in patients with stage 3-4 chronic kidney disease, with median time-averaged changes up to -89% versus +7% (p<0.0001).
Overview
Supports moving IL-6 inhibition into larger outcome trials in high-inflammatory-risk CKD; does not yet change practice.
Discussion
TRANQUILITY has reported — post the first read.
Expert takes
Sentiment overview
The TRANQUILITY trial is a Phase 2, randomized, placebo-controlled study evaluating monthly and quarterly subcutaneous dosing of pacibekitug (an anti-IL-6 monoclonal antibody) in patients with elevated hs-CRP and chronic kidney disease. All pacibekitug arms achieved rapid, deep, and durable hs-CRP reductions through Day 90 compared to placebo (p<0.0001 for all arms), with the 50 mg quarterly arm achieving >85% hs-CRP reductions — making pacibekitug the first IL-6 inhibitor to demonstrate deep hs-CRP reductions with quarterly dosing. Safety was comparable to placebo.
Key Points
- To evaluate the efficacy and safety of the long-acting interleukin-6 monoclonal antibody pacibekitug in reducing inflammatory markers in patients with stage 3–4 chronic kidney disease.
- Phase II randomized trial across 49 US centers enrolling 143 patients (mean age 69 years; 64% women) with stage 3–4 chronic kidney disease and elevated hs-CRP (2 to <15 mg/L).
- Participants were randomized 1:1:1:1 to subcutaneous pacibekitug (25 mg every 90 days, 50 mg every 90 days, or 15 mg every 30 days) or placebo for six months.
- Median time-averaged change in hs-CRP from baseline through day 180 was +7% with placebo compared to −76% with 25 mg every 90 days, −85% with 50 mg every 90 days, and −89% with 15 mg every 30 days (all p<0.0001 vs placebo).
- Pacibekitug also reduced fibrinogen and lipoprotein(a) levels and was well tolerated, with an overall discontinuation rate of 1.9% and no clear dose-related safety signals.
Study Design
Type
RCT (n=143)
Randomization
1:1:1:1
Multicenter
Yes
Structured PICO
Does subcutaneous pacibekitug reduce hs-CRP in patients with stage 3-4 chronic kidney disease and elevated hs-CRP?
P
Population
143 patients (mean age 69, 64% women) with stage 3-4 chronic kidney disease and elevated hs-CRP, followed for six months.
I
Intervention
Subcutaneous pacibekitug 25 mg or 50 mg every 90 days, or 15 mg every 30 days for six months.
C
Comparator
Placebo for six months.
O
Outcome
Median time-averaged change from baseline in hs-CRP through day 180.surrogate
The long-acting IL-6 inhibitor pacibekitug produced significant, dose-dependent reductions in hs-CRP among patients with stage 3-4 CKD and high cardiovascular risk.
Main Result
Absolute Event Rate: -89% vs 7%
p-value: p=<0.0001
Limitations
- No simultaneous results paper was available at presentation; source is a press release