Serum GFAP above the 84th percentile was associated with 40% higher risk of silent MS progression

Design

Prospective observational study in two independent cohorts (SMSC, EPIC)

Population

2,329 people with MS with serial serum NfL and GFAP (18,629 measurements)

Primary outcome

Progression independent of relapse activity (PIRA)

Effect

GFAP z >1.0: HR 1.45 (95% CI 1.21–1.75) SMSC; HR 1.36 (1.07–1.71) EPIC

This prospective study drew on two long-running cohorts: 1,709 people in the Swiss MS Cohort followed for a median 6.9 years and 620 in the US EPIC cohort followed for 13.1 years, with 18,629 paired blood measurements of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). The outcome was progression independent of relapse activity (PIRA) — confirmed disability worsening without a relapse.

High NfL was associated with relapse in the following year; high GFAP with PIRA. A GFAP z score above 1.0 was associated with higher PIRA risk in the next interval of about a year (HR 1.45, 95% CI 1.21–1.75 in the Swiss cohort; HR 1.36, 1.07–1.71 in EPIC). In the Swiss cohort, each yearly one-unit fall in GFAP z score during the first two years of fingolimod or B-cell-depleting therapy was associated with lower subsequent PIRA risk (HR 0.46 and 0.33).

The two markers appear to track different processes: NfL the inflammatory, relapsing side; GFAP the astrocytic, smouldering side that drives progression most current drugs do little for. Replication in a second cohort strengthens the finding. It is still observational, and serum GFAP is not widely available as a routine test; for now it is a tool for trials and specialist centres, not a routine clinic test.

• Look for disability worsening between relapses at every review — PIRA is common and easily missed.
• Where serum GFAP is available, a raised z score may justify closer follow-up for progression.
• Interpret NfL and GFAP together: NfL for relapse activity, GFAP for progression risk.
• Do not change therapy on a GFAP value alone; no trial has tested GFAP-guided treatment.
• Record 9-hole peg and timed 25-foot walk, which pick up progression earlier than EDSS.

Why it matters

It offers the first blood measure that tracks the progression most disease-modifying drugs fail to stop.

Don't overread it

Observational association in cohorts — falling GFAP on treatment is linked to lower risk but has not been shown to guide therapy.

The statistics, in plain English

An HR of 1.45 means about 45% higher risk in the following year for people with high GFAP. The two cohorts gave similar numbers, which makes a chance finding less likely. A z score of 1.0 means about one standard deviation above the age-adjusted reference.

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