Transitioning From S1P Receptor Modulators to B Cell–Depleting Therapies in Multiple Sclerosis

Abstract

Background and ObjectivesPatients with multiple sclerosis (MS) transition from oral sphingosine-1-receptor (S1P) modulators to anti-CD20 therapies for several circumstances. Optimal timing of this transition is uncertain, given competing concerns of rebound disease activity and ensuring immune reconstitution. The objective of this study was to evaluate the relationship between inflammatory activity and the transition period from fingolimod to anti-CD20 therapies in a real-world MS cohort.MethodsMedical records were reviewed for all patients at our center transitioning from fingolimod to rituximab or ocrelizumab between 2010 and October 2020. Time periods reviewed were the following: before fingolimod discontinuation, interval between fingolimod and anti-CD20 treatments, and after the first anti-CD20 infusion. The primary outcome was clinical relapses; MRI activity, time to absolute lymphocyte count (ALC) recovery, and infections were secondary. Clinical and demographic factors significant in univariable analyses were included in multivariable analyses.ResultsTransition data were available for 108 patients (68.5% women, 68.5% relapsing-remitting MS, mean age 44.6 years). The median (interquartile range) interval between fingolimod and anti-CD20 therapy was 28 (1–115.2) days. Six of 51 patients (11.8%) with intervals >1 month and 0/57 patients with shorter intervals experienced a relapse (MRI confirmed) within 6 months of fingolimod discontinuation. In the year following anti-CD20 initiation, 4/108 patients (3.7%) experienced a relapse (median 214.5 days after infusion). An additional 7% of those undergoing contrast-enhanced MRIs developed Gd+ lesions. ALC normalized following treatment switch in 89/92; the interval between treatments was unrelated to ALC recovery or infection.DiscussionDelaying anti-CD20 start to monitor ALC after S1P modulator discontinuation may not be necessary and could increase rebound risk. ALC monitoring could instead occur after a rapid switch to anti-CD20 treatment.

Effect of Prior Treatment With Fingolimod on Early and Late Response to Rituximab/Ocrelizumab in Patients With Multiple Sclerosis

“…Rowles et al described evolution of patients switching from fingolimod to BCDT with a shorter washout period (median 28 days) and evidenced no relapse within the first 6 months of treatment in patients with a washout period <1 month. 17 We evidenced very similar results in this study in a group of patients with a short washout duration. We also compared here the potential risk of reactivation between fingolimod and another prior DMT.…”

“…Previous studies clearly demonstrated that MS disease reactivation is frequent and could be acute after fingolimod withdrawal. 14 - 16 Recent studies specifically assessed the switch from fingolimod to BCDT 4 - 6 , 17 and found a long washout period in patients switching from fingolimod to BCDT associated with risk of relapse. Zhong et al 6 reported a higher risk of relapse within the first 3 months of OCR for patients switching from fingolimod with a mean washout period of 48.5 days than for patients who previously received another DMT.…”

“…Importantly, no patients with a washout period <25 days experienced relapse within the first 6 months of RTX/OCR as previously evidenced. 17 Hence, the risk of early disease reactivation after switching from fingolimod to BCDT may be driven by only the washout period duration and not a potential inherent effect of fingolimod on the future response to BCDT.…”

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

“…MS is an autoimmune demyelinating and neurodegenerative disease associated with derailments of the innate and adaptive immune system. While its entire immunopathogenesis is not fully clear, current notions posit that T and B cells, macrophages, monocytes, and microglia (endogenous phagocytes of the CNS) are involved, [19][20][21][22][23][24][25][26][27] (Figure 1).…”

High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis

“…Rebound activity has been reported following discontinuation of sequestering therapies, such as fingolimod [98][99][100] and natalizumab [101][102][103]. However, rapid switch to an anti-CD20 treatment, such as ocrelizumab, may reduce this rebound risk [104].…”