One of the most insidious challenges in the management of multiple sclerosis (SM) is represented today by those who, although they are clinically and radiologically stable, hide a silent disease activity. This is the case of the so-called apparently stable patient: a condition that can be recognized thanks to clinical observation, a continuous and open medical-patient dialogue and with the use of innovative biomarkers. In this context, the light chain neurophysions (NFL) – proteins issued in the blood following a neuro -axonal damage, initially designed in the research field and today also approved for clinical use (CE certification) – are emerging as biomarkers capable of early and reliable the disease activity not detectable by magnetic resonance imaging, allowing specialists to guide in a more precise way and timely therapeutic decisions and to improve the personalized management of the disease.
The use of NFL as a biomarator in multiple sclerosis represents a promising tool. However, despite their great potential, the systematic use in clinical practice is still limited by obstacles such as access to tests, costs and the absence of validated clinical algorithms. To contribute to sensitizing the scientific community on the possible adoption of this analysis tool in clinical practice, Novartis, in collaboration with Synlab, has started a centralized reading program that will involve up to 50 SM centers in Italy, each of which can analyze 40 blood samples. The initiative allows neurologists to acquire direct experience of this analysis tool, to optimize the management of patients and to contribute to the evolution of therapeutic paths.
The prognostic value of the NFL – Novartis informs in a note – has been confirmed by several clinical studies, including a large multicentric observational study, published in ‘The Lancet Neurology’, which has followed 814 patients with new -diagnosis recurrence, recruited in 22 centers for 4 years. The results showed that higher NFL higher serum levels, measured with single molecule technology, are associated with the presence of active lesions to magnetic resonance imaging, a greater risk of clinical repercussions and the need to intensify therapy over time. A recent prospective study, published in March 2025 on ‘Frontiers in Neurology’ analyzed the wide available literature confirming the key role of the NFL also in patients in apparent clinical and radiological stability. The results showed that a high value of NFL in the blood is strongly associated with an increased risk of losing the state of Neda-3 (no evidence of disease activity) within the following year. In addition, NFL levels are often high in the presence of subclinical symptoms such as persistent fatigue, sudden debut of anxiety or depression, slight cognitive alterations not associated with new injuries visible to magnetic resonance imaging.
In these cases, the use of the NFL as an early alert biomarker can guide the neurologist towards a closer monitoring with more frequent magnetic resonances, or a modification of the therapeutic strategy, even in the absence of ‘traditional’ signals of activity. “The timely identification of the patient with only apparent disease stability thanks to the measurement of plasma neurofilaments allows us to anticipate the therapeutic choices and adopt, immediately, high -effective treatments aimed at better control of the disease even in the long run – says Diego Centonze, full professor of Neurology University Tor Vergata -Roma and director of the Unit of Neurology of the IRCCS Neuromed of Pozzilli – integrating this. Biomarator in clinical practice means making a real change of paradigm: switching from a reactive approach, based on the appearance of clinical or radiological signs, to a proactive model, focused on the early risk identification and the dynamic personalization of the treatment “.
In these patients – continues the note – the biological data provided by the NFL can anticipate a clinical worsening and evaluate early a possible therapeutic escalation. Highly effective treatments, already widely validated in clinical studies and in real practice, have proven to be able to reduce the levels of NFL in the blood, control the inflammatory activity and, above all, slow down the progression of disability. In addition, in many patients it is possible to use high -efficiency home administration, with a consequent improvement not only of the prognosis but also of the quality of life of the person with sm. “The dosage of plasma neurofilaments is a precious tool, but cannot be interpreted alone: it must always be integrated with magnetic resonance imaging and clinical evaluation – clarifies Centonze – only through this combined reading can we guarantee a more timely control of the disease. In this path, the patient’s role is central: it is essential to encourage him to report even the lighter symptoms. A continuous and transparent dialogue is essential to improve clinical results and face multiple sclerosis in a more conscious and shared way “.
The structured integration of this biomarator in the PDTAs, the therapeutic welfare diagnostic paths, would represent a significant step forward towards a more timely management, aware and oriented towards the prevention of neurological damage. “As a company engaged for years in the multiple sclerosis area, complex pathology whose management is constantly evolving – declares Paola Coco, Chief Scientific Officer and Medical Affairs Head Novartis Italia – We believe that innovation must be accessible and translate into concrete tools to improve clinical practice and, above all, the life of patients. Our commitment goes in this direction: contributing to the evolution of the national health service promoting models more early, effective and sustainable management, in the interest of patients and the scientific community “.
