Ianalumab lowered Sjögren activity scores slightly, but not symptoms

Design

Two 52-week, double-blind, placebo-controlled phase 3 randomised trials (NEPTUNUS-1 and -2)

Population

779 adults with active Sjögren's disease

Primary outcome

Change in ESSDAI at week 48

Effect

Monthly ianalumab vs placebo −1.3 (95% CI −2.6 to 0.0) and −1.0 (−2.0 to 0.0); no symptom score difference

NEPTUNUS-1 and NEPTUNUS-2 were 52-week double-blind trials of ianalumab, a monoclonal antibody that depletes B cells and blocks the BAFF receptor, in 779 people with active Sjögren's disease. Patients received 300 mg subcutaneously monthly or, in one trial, every three months, or placebo.

In both trials, monthly ianalumab reduced the ESSDAI disease activity score more than placebo at week 48, by about 1.0 to 1.3 points on a scale running to 123. Both results only just reached statistical significance. There was no difference in the proportion achieving a meaningful ESSDAI response, and no improvement in patient-reported dryness, fatigue or pain scores. Serious adverse events were similar; injection reactions were more common.

These are the first phase 3 trials of a targeted therapy to meet their primary endpoint in Sjögren's, which matters for the field. But a one-point difference in ESSDAI without any change in how patients feel is a small clinical gain.

Regulatory status is unknown in India and elsewhere. For now, management of Sjögren's remains symptomatic for glandular disease and targeted at organ involvement for systemic disease.

• Do not expect ianalumab to relieve dryness or fatigue, based on these trials.
• Continue symptomatic management of glandular Sjögren's disease.
• Treat systemic organ involvement according to current recommendations.
• Watch for regulatory decisions before considering ianalumab outside trials.

Why it matters

It is a first positive phase 3 signal in a disease with no targeted therapy, but a much smaller one than patients need.

Don't overread it

Statistically positive on the primary endpoint, but secondary and patient-reported outcomes showed no benefit.

The statistics, in plain English

Differences of −1.3 and −1.0 points had confidence intervals reaching 0.0, so both results sit right at the edge of significance. On a 123-point scale, a one-point change is small, and the lack of any symptom benefit makes its clinical value uncertain.

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