Reviews/Psoriasis Psoriatic Arthritis/HLA-Cw6 predicts ustekinumab response
Psa BMK · PSA-BMK-01 · v2
Several separate patient groups found that people carrying the HLA-Cw6 marker tended to clear their psoriasis better on ustekinumab than people without it [1][4], and the large combined analysis of the drug's main trials confirmed that the two groups respond differently [2]. But that same analysis stressed the gap between groups is small, and it shrinks when you ask for near-complete skin clearance or look later in treatment [2]. Two single-centre studies looking back at their own patients could not find any difference at all [5][6]. One study saw no difference early on but did see one much later, at week 48 [7]. So the marker points in a consistent direction where it shows up, but how large and how reliable that advantage is remains unsettled.
Independent cohorts report that Cw6-positive patients respond better to ustekinumab, with Chiu reporting PASI 75 at week 4 of 38% versus 9% (P=0.019) and PASI 90 at week 28 of 63% versus 26% (P=0.035) [1], and Galluzzo confirming HLA-Cw6 as a positive predictor of response [4]. The pooled Phase 3 program confirms a differential response (86% versus 76% PASI 75 at week 24) but describes it as modest, particularly at PASI 90/100 and later time points [2]. A predictive-biomarker analysis found Cw6-negative patients more likely to respond to adalimumab than ustekinumab (OR 2.95 at 6 months), implying a relative advantage for Cw6-positive patients on ustekinumab [3]. Against this, two monocentric retrospective cohorts found no significant difference in response, one reporting P=0.164 [5][6], and one cohort found an effect only at week 48 and not at week 16 [7]. The contested point: The evidence divides on magnitude and replication rather than direction: no study reports a reverse effect, but the strongest dataset bounds the advantage as modest and attenuating [2], while two cohorts detect no significant difference at all [5][6]. Whether the association is robust across response thresholds and across the treatment course is the open point [2][7].
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The strongest dataset [2] confirms a differential but explicitly calls it modest and attenuating at PASI 90/100 and later timepoints, undercutting the unqualified word 'superior' in the claim.
Two monocentric retrospective cohorts [5][6] found no significant difference (P=0.164), so the association is not consistently replicated.
Where it remains uncertain. The pooled program calls the differential modest and attenuating at PASI 90/100 and later [2], and two monocentric cohorts found no significant difference (P=0.164) [5][6].
Aleatory
Supportive cohorts are small and retrospective, so genotype-response differences carry wide sampling variability with N largely unreported [1][5][6][7].
Epistemic
Two monocentric cohorts detect no significant difference (P=0.164) while others do, so the true effect and its conditions are not yet pinned down [5][6][2].
Inferential
[3] infers a Cw6-positive ustekinumab advantage from Cw6-negative patients favouring adalimumab (OR 2.95), not from a direct genotype comparison on ustekinumab.
The load-bearing papers from a corpus of 8, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Primary supporting evidence of superior early response in Cw6+.
“More HLA-Cw6-positive patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative patients (38% vs. 9%, P = 0.019).”
Panel auditInternal validity: low · scope of inference: Chinese psoriasis patients on ustekinumab; early (week 4) and later (week 28) PASI response by Cw6 status.Key limitations: retrospective design · sample size not reported · single ethnicity/single centre
Largest dataset confirms the association but bounds its magnitude as modest.
“A differential response has been confirmed in HLA-C*06:02-positive versus negative patients; however, this difference is modest, particularly at higher response thresholds (PASI 90/100) and later time points.”
Panel auditInternal validity: medium · scope of inference: Phase 3 trial population on ustekinumab; PASI 75/90/100 response by Cw6 status across time points.Key limitations: difference described as modest · attenuates at PASI 90/100 and later time points · no p-value or N in abstract
Indirect support via relative response favouring ustekinumab in Cw6+.
“HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (OR 2.95 at 6 months)”
Panel auditInternal validity: medium · scope of inference: Severe psoriasis patients (including psoriatic arthritis) choosing between adalimumab and ustekinumab by Cw6 status.Key limitations: indirect: drug comparison not within-ustekinumab Cw6 contrast · sample size not reported · effect concentrated in psoriatic arthritis subgroup
3 of 8 papers shown. The full review lists all of them, with the panel’s arbitration →
Claims are graded at each quarterly release, and re-graded between releases only when a pivotal trial lands. Every change is a new version of the claim.
A directionally consistent but modest and incompletely replicated association warrants Uncertain rather than a firmer tier.
Release 2026-q4 re-graded every claim from its corpus under protocol v0.19. An earlier release's grade is shown for the record; it came from an earlier protocol and is not a movement.
Assumptions that carry weight but are not themselves established.
The panel records the gap that would most move the claim, and the study that would close it.
Prospective genotype-stratified ustekinumab trial. The direct question — do Cw6-positive patients respond better on ustekinumab — rests on retrospective cohorts that disagree [1][5][6]; only a prospective stratified design would resolve magnitude and replication. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: Prospective ustekinumab cohort powered to compare Cw6-positive versus negative PASI response at pre-specified thresholds and timepoints.
Open question: Does the Cw6-positive advantage on ustekinumab persist at stringent response thresholds (PASI 90/100)? Why it is still open: The pooled program confirms a differential but reports it attenuates at higher thresholds [2].
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 18 Sep 2026 · protocol v0.19