Nemolizumab misses its primary endpoint in dialysis-associated itch

Design

Randomised, placebo-controlled trial, 12 weeks

Population

258 haemodialysis patients with chronic kidney disease-associated pruritus

Primary outcome

≥4-point improvement in worst-itch NRS at week 12

Effect

47.7% (60 mg) and 38.5% (30 mg) vs 32.4% placebo; not significant

NIKAIA-1 randomised 258 haemodialysis patients with chronic kidney disease-associated pruritus to nemolizumab 30 mg or 60 mg every four weeks, or placebo, for 12 weeks.

The primary endpoint, a 4-point or greater improvement in worst-itch score at week 12, was not met: 47.7% on 60 mg (P = .07) and 38.5% on 30 mg vs 32.4% on placebo. Itch-related quality of life improved on the higher dose (nominal P < .01), and itch fell quickly: at week 4, 24.3 to 26.6% vs 7.4% had a 4-point improvement. Drug-related adverse events were similar across groups.

This is a negative trial for its main question. The early separation and high placebo response suggest the IL-31 pathway may play some part in uraemic itch, but that is hypothesis-generating. For now, nemolizumab is not an evidence-based option for dialysis itch.

• Do not use nemolizumab for chronic kidney disease-associated pruritus on the basis of this trial.
• Check dialysis adequacy, phosphate, parathyroid hormone and dry skin first in any dialysis patient with itch.
• Use emollients and consider gabapentinoids at renally adjusted doses, and difelikefalin where available.
• Expect a large placebo response in itch trials; one in three improved on placebo here.

Why it matters

IL-31 blockade works in atopic dermatitis and prurigo nodularis, but that did not carry over to uraemic itch.

Don't overread it

The quality-of-life and week-4 results are secondary and nominal; they do not rescue a missed primary endpoint.

The statistics, in plain English

A P value of .07 means the difference between 47.7% and 32.4% could plausibly be chance by the trial's prespecified standard. Nominal P values for secondary outcomes are not corrected for multiple testing, so they carry less weight.

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