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TRANQUILITYPreventionOpen Access
Monthly and quarterly pacibekitug in patients with chronic kidney disease at high cardiovascular risk
Key result
Pacibekitug cuts hs-CRP by up to ~89% versus placebo in patients with CKD.
- P<0.0001
- n=143
Why the trial?
IL-6-driven inflammation contributes to cardiovascular risk in chronic kidney disease, but durable IL-6 blockade with infrequent dosing had not been established. TRANQUILITY tested whether monthly or quarterly pacibekitug sustainably lowers hs-CRP with acceptable safety in stage 3-4 CKD at high cardiovascular risk.
Does subcutaneous pacibekitug reduce hs-CRP in patients with stage 3-4 chronic kidney disease and elevated hs-CRP?
Population
143 patients with stage 3-4 CKD and hs-CRP 2 to <15 mg/L (mean age 69, 64% women)
Comparison
Pacibekitug SC 25 mg q90d, 50 mg q90d, or 15 mg q30d vs placebo
Design
Phase 2 multicenter randomized placebo-controlled dose-ranging trial (49 US centres)
Follow-up
6 months (day 180)
Authors
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts see TRANQUILITY as strong proof that pacibekitug suppresses inflammation in CKD patients, but stress that biomarker reduction alone does not prove cardiovascular benefit, especially after ZEUS showed a similar IL-6 strategy failed to reduce MACE.
Clinicians acknowledge the sustained and dose-dependent lowering of hs-CRP as impressive target engagement, particularly with quarterly dosing. However, several voices flag the ZEUS trial, which showed that deep IL-6 suppression with a different antibody did not translate into fewer cardiovascular events. The central question now is whether pacibekitug can succeed where ziltivekimab did not, and whether phase 3 outcomes data will justify continued development.
Agreement
Multiple clinicians agree that TRANQUILITY demonstrates compelling target engagement but caution that hs-CRP reduction does not equal cardiovascular benefit, citing the negative ZEUS trial of ziltivekimab as a critical precedent.
2 clinicians say this directly
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Still unclear
Whether pacibekitug's mechanism or dosing advantages can produce the MACE reduction that ziltivekimab failed to deliver in ZEUS remains unanswered. Experts note that hs-CRP is a pathway marker, not a clinical endpoint, so phase 3 outcomes trials are essential before any practice implications emerge.
Key expert perspectives
ZEUS showed another IL-6 inhibitor lowered hsCRP but produced no MACE benefit
Framed TRANQUILITY within the residual inflammatory risk landscape but flagged that ZEUS, testing ziltivekimab in over 6,300 patients with ASCVD, CKD, and inflammation, showed clear IL-6 target engagement and substantial hsCRP lowering yet no MACE benefit.
Quarterly dosing achieved persistent hsCRP reduction but the effect disappeared when treatment stopped
Noted that quarterly pacibekitug achieved significant and persistent hsCRP reduction through 180 days with no safety concerns, but pointed out the effect disappeared after day 180 when treatment was stopped.
Distilled from their postX post
DLDeepak L. BhattDirector, Mount Sinai Fuster Heart HospitalResults readoutBefore results
Quarterly pacibekitug produced large hs-CRP reductions and merits phase 3 testing
Highlighted that pacibekitug demonstrated rapid, deep, and consistent hs-CRP reductions across subgroups including sex, body mass index, diabetes status, and baseline GLP-1 and GIP/GLP-1 receptor agonist use. Concluded that the data make a strong case for continued evaluation in atherosclerotic cardiovascular disease and other inflammation-driven cardiovascular diseases.
Implication
Supports moving IL-6 inhibition into larger outcome trials in high-inflammatory-risk CKD; does not yet change practice.
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.
Evidence details
What drove the result?
| Outcome | Placebo | 25 mg q90d | 50 mg q90d | 15 mg q30d |
|---|---|---|---|---|
| hs-CRP, median time-averaged change to day 180 | +7% | -76% | -85% | -89% |
| Dose-dependent; all p<0.0001 vs placebo; sustained from day 30 | ||||
Limitations & tradeoffs
Safety
Treatment discontinuations 1.9% overall with no clear dose-related safety signals (per-arm counts not reported).
Design limitations
phase 2 trial with a biomarker (hs-CRP) endpoint, not clinical outcomes, and results come from the congress press release with no simultaneous publication.
Statistical certainty
only 143 patients across four arms.
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
Main Result
Absolute Event Rate: -89% vs 7%
p-value: p=<0.0001
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.
Limitations
- No simultaneous results paper was available at presentation; source is a press release
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Deepak Bhatt (2026) conducted an RCT in Stage 3-4 chronic kidney disease and elevated hs-CRP (n=143). Pacibekitug vs. Placebo was evaluated on Median time-averaged change from baseline in hs-CRP through day 180 (p=<0.0001). 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).