Comparison of rituximab originator (MabThera ® ) to biosimilar (Truxima ® ) in patients with multiple sclerosis

International audienceBackground: Rituximab’s originator MabThera ® or Rituxan ® has demonstrated high efficacy in multiple sclerosis (MS). Because of the patent expiration, rituximab biosimilars have been developed. However, because a biosimilar is not the exact copy of the originator, the efficacy and safety of a biosimilar may significantly differ. Objectives: To compare the efficacy and safety of the biosimilar Truxima ® and the originator MabThera ® in MS. Methods: Consecutive MS patients receiving MabThera ® or Truxima ® were prospectively followed during 1 year after treatment introduction. Allocation to each treatment depended on the period of introduction and not the physician’s choice. Lymphocyte count, clinical and magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS), and adverse events were compared. Results: In total, 105 and 40 patients received MabThera ® and Truxima ® , respectively. The two groups did not differ in baseline characteristics. Effect on CD19+ lymphocytes and disease activity were similar during follow-up. EDSS remained stable, with no difference between groups. Adverse events were similar between groups. Conclusion: The efficacy and safety of the rituximab biosimilar Truxima ® seem equivalent to the originator MabThera ® in MS patients. Truxima ® could represent a relatively cheap and safe therapeutic alternative to MabThera ® and could improve access to highly efficient therapy for MS in low- or middle-income countries

Comparison of the Response to Rituximab between Myelin Oligodendrocyte Glycoprotein and Aquaporin‐4 Antibody Diseases

International audienceObjective To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies. Methods We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes. Results In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range = 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001). Interpretation In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant, because one-third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody-associated disorder. ANN NEUROL 201

Improvement of spasticity following intermittent theta burst stimulation in multiple sclerosis is associated with modulation of resting-state functional connectivity of the primary motor cortices

International audienceBACKGROUND: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. OBJECTIVE: To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. METHODS: A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. RESULTS: At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group (p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex (p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). CONCLUSION: This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS

Efficacy of rituximab in refractory RRMS

International audienceObjective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT).Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts.Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001).Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT

Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

International audienceBackground: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk.Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS).Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal.Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations.Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS

sj-docx-2-msj-10.1177_13524585231223880 – Supplemental material for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

Supplemental material, sj-docx-2-msj-10.1177_13524585231223880 for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society by Nicolas Collongues, Françoise Durand-Dubief, Christine Lebrun-Frenay, Bertrand Audoin, Xavier Ayrignac, Caroline Bensa, Kévin Bigaut, Bertrand Bourre, Clarisse Carra-Dallière, Jonathan Ciron, Gilles Defer, Arnaud Kwiatkowski, Emmanuelle Leray, Elisabeth Maillart, Romain Marignier, Guillaume Mathey, Nathalie Morel, Eric Thouvenot, Hélène Zèphir, Julie Boucher, Clémence Boutière, Pierre Branger, Angélique Da Silva, Sarah Demortière, Maxime Guillaume, Benjamin Hebant, Edouard Januel, Anne Kerbrat, Eric Manchon, Xavier Moisset, Alexis Montcuquet, Chloé Pierret, Julie Pique, Julien Poupart, Chloé Prunis, Thomas Roux, Perrine Schmitt, Géraldine Androdias and Mikael Cohen in Multiple Sclerosis Journal</p

sj-docx-3-msj-10.1177_13524585231223880 – Supplemental material for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

Supplemental material, sj-docx-3-msj-10.1177_13524585231223880 for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society by Nicolas Collongues, Françoise Durand-Dubief, Christine Lebrun-Frenay, Bertrand Audoin, Xavier Ayrignac, Caroline Bensa, Kévin Bigaut, Bertrand Bourre, Clarisse Carra-Dallière, Jonathan Ciron, Gilles Defer, Arnaud Kwiatkowski, Emmanuelle Leray, Elisabeth Maillart, Romain Marignier, Guillaume Mathey, Nathalie Morel, Eric Thouvenot, Hélène Zèphir, Julie Boucher, Clémence Boutière, Pierre Branger, Angélique Da Silva, Sarah Demortière, Maxime Guillaume, Benjamin Hebant, Edouard Januel, Anne Kerbrat, Eric Manchon, Xavier Moisset, Alexis Montcuquet, Chloé Pierret, Julie Pique, Julien Poupart, Chloé Prunis, Thomas Roux, Perrine Schmitt, Géraldine Androdias and Mikael Cohen in Multiple Sclerosis Journal</p

sj-docx-4-msj-10.1177_13524585231223880 – Supplemental material for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

Supplemental material, sj-docx-4-msj-10.1177_13524585231223880 for Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society by Nicolas Collongues, Françoise Durand-Dubief, Christine Lebrun-Frenay, Bertrand Audoin, Xavier Ayrignac, Caroline Bensa, Kévin Bigaut, Bertrand Bourre, Clarisse Carra-Dallière, Jonathan Ciron, Gilles Defer, Arnaud Kwiatkowski, Emmanuelle Leray, Elisabeth Maillart, Romain Marignier, Guillaume Mathey, Nathalie Morel, Eric Thouvenot, Hélène Zèphir, Julie Boucher, Clémence Boutière, Pierre Branger, Angélique Da Silva, Sarah Demortière, Maxime Guillaume, Benjamin Hebant, Edouard Januel, Anne Kerbrat, Eric Manchon, Xavier Moisset, Alexis Montcuquet, Chloé Pierret, Julie Pique, Julien Poupart, Chloé Prunis, Thomas Roux, Perrine Schmitt, Géraldine Androdias and Mikael Cohen in Multiple Sclerosis Journal</p