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Transitioning From S1P Receptor Modulators to B Cell-Depleting Therapies in Multiple Sclerosis: Clinical,
William M Rowles1, Wan-Yu Hsu1, Kira McPolin1
1From the UCSF Weill Institute for Neurosciences (W.M.R., W.-Y.H., K.M., A.L., C.-Y.G., A.J.G., J.M.G., R.M.B.), Division of Neuroimmunology and Glial Biology, Department of Neurology, Department of Clinical Pharmacy (S.M.), and UCSF Department of Ophthalmology (A.J.G.), University of California, San Francisco.
Background And Objectives:
Patients 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.
Methods:
Medical 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.
Results:
Transition 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.
Discussion:
Delaying 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.
Insights
Transitioning from sphingosine-1-receptor (S1P) modulators to anti-CD20 therapies in multiple sclerosis (MS) patients may not require a long interval for immune reconstitution. Shorter intervals between treatments appear safe and may reduce relapse risk.
Area of Science:
- Neurology
- Immunology
- Pharmacology
Background:
- Patients with multiple sclerosis (MS) often switch from oral sphingosine-1-receptor (S1P) modulators to anti-CD20 therapies.
- The optimal timing for this transition is unclear, balancing rebound disease activity and immune reconstitution.
- This study investigates inflammatory activity during the transition from fingolimod to anti-CD20 treatments in a real-world MS cohort.
Purpose of the Study:
- To evaluate the relationship between inflammatory activity and the transition period from fingolimod to anti-CD20 therapies.
- To assess relapse rates, MRI activity, lymphocyte count recovery, and infections in MS patients undergoing this switch.
- To inform clinical practice regarding the timing of switching disease-modifying therapies in MS.
Main Methods:
- Retrospective review of medical records for 108 MS patients transitioning from fingolimod to rituximab or ocrelizumab (2010-2020).
- Analysis of time intervals between fingolimod discontinuation and anti-CD20 initiation.
- Primary outcome: clinical relapses; secondary outcomes: MRI activity, absolute lymphocyte count (ALC) recovery, and infections.
Main Results:
- A median interval of 28 days was observed between fingolimod and anti-CD20 therapy.
- Six of 51 patients (11.8%) with intervals >1 month relapsed within 6 months of discontinuation; none with shorter intervals did.
- Relapses post-anti-CD20 initiation were infrequent (3.7%), and ALC normalized in most patients (89/92) regardless of the treatment interval.
Conclusions:
- Delaying anti-CD20 therapy to monitor ALC after S1P modulator discontinuation may not be necessary and could increase rebound risk.
- A rapid switch to anti-CD20 treatment is feasible and potentially safer.
- ALC monitoring could be performed after initiating anti-CD20 therapy instead of delaying treatment.
