Systemic sclerosis & Raynaud's
Neutrophil-to-lymphocyte ratio as a biomarker for disease onset and mortality risk in SSc: a real-world national cohort study
Authors' conclusion
Our study suggests that an increase in NLR marks the onset of disease in a subset of SSc patients with poor outcomes. An NLR value above 4 at diagnosis identifies patients at high risk for mortality.
Study context
- Population
- Adult SSc patients from Maccabi Healthcare Services, 1998–2023, identified by ICD-9 codes with serological confirmation; steroid users excluded1,232 with baseline neutrophil-to-lymphocyte ratio (NLR)
- Participants
- 1,511 patients
- Exposure
- NLR categories at diagnosis
- Outcome
- Mortality by NLR at diagnosis
Methodological detailsreal-world national cohort, multivariable Cox regression
- Real-world national cohort
- Multivariable Cox regression
Main finding
As reported in the abstract
Mortality (multivariable Cox, adjusted for age, sex, ILD and pulmonary hypertension)
Hazard ratio
1.7
P = 0.025
NLR ≥ 3
Hazard ratio
2.8
P < 0.001
NLR ≥4
- Clear stepwise decline in 5- and 10-year survival with increasing NLR (Kaplan-Meier, four categories)
- log-rank P < 0.001
Observational data: associations, not effects.
Further findings
| Outcome | Values |
|---|---|
| NLR at disease onset vs 1-15 years prior, in patients with baseline NLR ≥ 3 | NLR ≥ 3 mean 4.4 ± 2.2 |
- NLR at disease onset vs 1-15 years prior, in patients with baseline NLR ≥ 3 — NLR increased significantly at disease onset compared with 1-15 years prior
- P < 0.01
- NLR at disease onset vs 1-15 years prior, in patients with baseline NLR ≥ 3: n = 191
Mean NLR at diagnosis (all patients with baseline NLR data)
- Mean NLR at diagnosis
- 2.2 ± 1.4
- 1232 patients with baseline NLR data
Longitudinal NLR after diagnosis · 15 years
- NLR remained persistently elevated over 15 years, unaffected by treatment
5- and 10-year survival by NLR category (0-1.99, 2.00-2.99, 3.00-3.99, ≥4.0), Kaplan-Meier · 5 and 10 years
- Clear stepwise decline in survival with increasing NLR
- log-rank P < 0.001
Original publication
Neutrophil-to-lymphocyte ratio as a biomarker for disease onset and mortality risk in SSc: a real-world national cohort study. Rheumatology (Oxford). Published 9 December 2025. doi:10.
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