Strategic positioning and long-term management of immune reconstitution therapies in multiple sclerosis: An expert consensus
Nikolaos Mitsoudis, Ioannis Nikolakakis, Konstantinos Aggelakis, Ermioni Giannouli, Antigoni Gouliovaki, Gerasimos Grammatikopoulos, Nikolaos Thanos, Antonios Kerasnoudis, Dimitra Kotzamani, Despoina Koutsodonti, Marianna Maltezou, Dimitris Naoumis, Pavlos Ntalos, Paraskevi Papageorgiou, Dimitra Papadimitriou, Stefania Alexia Sotirli, Akrivi Antonakopoulou, Spyros N. Deftereos, Ioannis Iliopoulos, Evangelos Kouremenos, Christos Bakirtzis, Marina Kleopatra Boziki, Panos Stathopoulos, Nikolaos GrigoriadisBackground
Immune Reconstitution Therapies (IRTs) represent a distinct class of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS), mainly characterized by transient as opposed to continuous immunosuppression. Dedicated guidelines on the long-term management of this class of drugs are lacking.
Objectives
This study aimed to define the positioning of IRTs, specifically Cladribine tablets, addressing patient selection, family planning, and long-term therapeutic strategies.
Design
An expert consensus study conducted between March and July 2025.
Methods
The Hellenic Academy of Neuroimmunology (HELANI) convened a Steering Committee and a 19-neurologist expert panel, selected among academic centers, public neurology departments and private hospitals/practices. Α three-round process was followed, comprising statement drafting, blinded online voting, and a face-to-face consensus meeting. Consensus required >80% agreement on a 5-point Likert scale.
Results
Of 24 initial assertions, 23 were retained for the final consensus framework. 22 achieved full consensus regarding both clinical principle and application. The panel established “Timely” high-efficacy intervention as the preferred treatment approach. Cladribine tablets were identified as the only IRT with sufficient data to support use in patients aged >55 years and was considered as appropriate for family planning without treatment interruption. One statement (vaccinations) was removed due to insufficient evidence. Regarding long-term management, consensus was achieved on the validity of re-treating clinically stable patients after Year 4; however, opposite views regarding the timing of re-treatment were expressed, advocating both continued maintenance and disease activity-driven approaches. Notably, Neurofilament Light (NfL) testing was unanimously rejected (0% agreement) as a standard monitoring tool.
Conclusion
This consensus establishes a framework for the timely Use and long-term management of IRTs. Cladribine serves as a central pillar, offering advantages in family planning and older populations, while re-treatment paradigms require personalized timing.