Authors:
Aleksandra Maleska Maceski (Basel | CH)
Pascal Benkert (Basel | CH)
Johanna Oechtering (Basel | CH)
Sabine Schaedelin (Basel | CH)
Amar Zadic (Basel | CH)
Juan Francesco Vilchez Gomez (Basel | CH)
Lester Melie-Garcia (Basel | CH)
Alessandro Cagol (Basel | CH)
Riccardo Galbusera (Basel | CH)
Suvitha Subramaniam (Basel | CH)
Johannes Lorscheider (Basel | CH)
Bettina Fischer-Barnicol (Basel | CH)
Lutz Achtnichts (Aarau | CH)
Olivier Findling (Aarau | CH)
Patrice Lalive (Geneva | CH)
Claire Bridel (Geneva | CH)
Stefanie Müller (St Gallen | CH)
Caroline Pot (Lausanne | CH)
Amandine Mathias (Lausanne | CH)
Renaud Du Pasquier (Lausanne | CH)
Anke Salmen (Bern | CH)
Robert Hoepner (Bern | CH)
Andrew Chan (Bern | CH)
Giulio Disanto (Lugano | CH)
Chiara Zecca (Lugano | CH)
Annette Orleth (Basel | CH)
Marcus D'Souza (Basel | CH)
Özgür Yaldizli (Basel | CH)
Tobias Derfuss (Basel | CH)
Claudio Gobbi (Lugano | CH)
Michael Khalil (Graz | AT)
Ahmed Abdelhak (San Francisco | US)
Bjoern Tackenberg (Basel | CH)
Jorge Oksenberg (San Francisco | US)
Heinz Wiendl (Münster | DE)
Fredrik Piehl (Stockholm | SE)
Klaus Berger (Münster | DE)
Marco Hermesdorf (Münster | DE)
David Conen (Hamilton | CA)
Andreas Buser (Basel | CH)
Ludwig Kappos (Basel | CH)
Cristina Granziera (Basel | CH)
David Leppert (Basel | CH)
Eline Willemse (Basel | CH)
Jens Kuhle (Basel | CH)
Abstract
Aims
Blood biomarkers that capture disease progression independent of relapse activity (PIRA) in MS are lacking. The aim of our study was to investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) levels in people with MS (PwMS) starting B cell depleting therapy (BCDT), and to study the association with future PIRA events.
Methods
Longitudinal data from 318 patients (1302 samples) under BCDT were leveraged from the Swiss MS Cohort. Serum GFAP levels were also determined in 2861 healthy controls (4943 samples), which served as a reference to calculate age-, sex- and BMI-adjusted Z scores allowing quantification of the deviation from normal. Biomarker levels were measured using an ultrasensitive Simoa assay in patients prospectively starting ocrelizumab or rituximab. Prognostic power of biomarkers at median one year after start of BCDT and their longitudinal dynamics in relation to PIRA were investigated.
Results
During a median of 4.1 [IQR: 3.0, 5.0] years from BCDT treatment initiation, 22.7% of PwMS experienced at least one PIRA event. Increased sGFAP levels (Z score > 1) one year after treatment initiation were associated with an increased hazard risk of PIRA (HR=1.9 95% confidence interval [1.1, 3.1], p = 0.015), whereas increased sNfL levels were not associated with increased risk (p = 0.41). Longitudinally, on-treatment sGFAP levels increased (estimate 0.61 Z score units per 10 years of follow-up time [0.39, 0.83], p < 0.001), and were higher in PwMS experiencing PIRA (estimate 0.38 Z score units [0.06, 0.71], p = 0.023) compared with those remaining stable. Different sNfL Z scores slopes were found in patients with PIRA vs. stable disease (interaction p = 0.008) with an average decrease of 0.98 Z score units per 10 years observed in stable patients (estimate -0.98 [-1.32, -0.64], p < 0.001), while elevated levels in PwMS later experiencing PIRA remained unaffected by BCDT.
Conclusions
Elevated serum GFAP, but not sNfL levels one year after BCDT initiation were prognostic of PIRA. The two biomarkers also displayed significantly different dynamics after starting BCDT; in patients later experiencing PIRA both sGFAP and sNfL levels remained higher than in PwMS with stable disease. Our findings emphasize the value of sNfL and especially sGFAP for capturing and prognosticating risk of disease progression in MS.