Discontinuation Of Fingolimod Research Articles

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity. To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET. This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022. Natalizumab, fingolimod, rituximab, and ocrelizumab. Time to first relapse. Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy. As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Multiple Sclerosis Disease Activity and Disability Following Cessation of Fingolimod for Pregnancy.

Discontinuation of fingolimod ≥2 months before pregnancy is recommended to minimize potential teratogenicity. The magnitude of MS pregnancy relapse risk, particularly severe relapses, after fingolimod cessation is unclear, as is whether this risk is reduced by pregnancy or modifiable factors. Pregnancies who stopped fingolimod treatment within 1 year before or during pregnancy were identified from the German MS and Pregnancy Registry. Data were collected through structured telephone-administered questionnaires and neurologists' notes. Severe relapses were defined as a ≥2.0 increase in Expanded Disability Status Scale (EDSS) or new or worsening relapse-related ambulatory impairment. Women who continued to meet this definition 1 year postpartum were classified as reaching the Severe Relapse Disability Composite Score (SRDCS). Multivariable models accounting for measures of disease severity and repeated events were used. Of the 213 pregnancies among 201 women (mean age at pregnancy onset 32 years) identified, 56.81% (n = 121) discontinued fingolimod after conception. Relapses during pregnancy (31.46%) and the postpartum year (44.60%) were common. Nine pregnancies had a severe relapse during pregnancy and additional 3 during the postpartum year. One year postpartum, 11 of these (6.32% of n = 174 with complete EDSS information) reached the SRDCS. Adjusted relapse rates during pregnancy were slightly higher compared with the year before pregnancy (relapse rate ratio = 1.24, 95% CI 0.91-1.68). Neither exclusive breastfeeding nor resuming fingolimod within 4 weeks of delivery were associated with a reduced risk of postpartum relapses. Most pregnancies relapsed during the first 3 months postpartum (n = 55/204, 26.96%). Relapses during pregnancy after fingolimod cessation are common. Approximately 6% of women will retain clinically meaningful disability from these pregnancy-related, fingolimod cessation relapses 1 year postpartum. This information should be shared with women on fingolimod desiring pregnancy, and optimizing MS treatment with nonteratogenic approaches should be discussed.

Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis.

Clinical and radiological signs of recurring disease activity (RDA) have been described in patients with multiple sclerosis (pwMS) after discontinuation of fingolimod (FGL). To describe frequency, severity and potential risk factors for RDA after FGL discontinuation in a large real-world cohort of pwMS. Post-FGL RDA was defined as evidence of clinical and/or radiological activity within 6 months after FGL discontinuation. Relapses with Expanded Disability Status Scale increase ⩾2 points and/or magnetic resonance imaging (MRI) activity with at least five cerebral gadolinium-enhancing lesions and/or ⩾6 cerebral new T2 lesions were defined as severe recurring disease activity (sRDA). Using a multivariate logistic model, we explored the influence of age, disease duration, sex, clinical, and MRI activity under FGL on the occurrence of RDA. We identified 110 pwMS who discontinued FGL. Thirty-seven (33.6%) developed post-FGL RDA and 13 (11.8%) also fulfilled criteria for sRDA. Younger age at diagnosis [odds ratio (OR) = 1.10, p < 0.01], shorter disease duration (OR = 1.17, p < 0.01), and MRI activity under FGL (OR = 2.92, p = 0.046) were independent risk factors for the occurrence of post-FGL RDA. Individual risk assessment and optimal treatment sequencing can help to minimize the risk of post-FGL RDA. Early switch to highly effective disease-modifying therapy might reduce occurrence of post-FGL RDA.

Progressive multifocal leukoencephalopathy or immune reconstitution inflammatory syndrome after fingolimod cessation? A case report

BackgroundFingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML); however, its discontinuation may cause severe immune reconstitution inflammatory syndrome (IRIS). As both of these conditions (especially fingolimod induced PML) are rarely described in medical case reports distinguishing between PML-IRIS and MS-IRIS may be diagnostically challenging.Case presentationWe report a patient with severe clinical decline (Expanded Disability Status Scale (EDSS) increasing from 3.5 to 7.5) and multiple, large, contrast-enhancing lesions on brain magnetic resonance imaging (MRI) a few months after fingolimod withdrawal. The diagnostic possibilities included IRIS due to fingolimod withdrawal versus PML-IRIS. The JC virus (JCV) antibody index was positive (2.56); however, cerebrospinal fluid (CSF) JCV real-time polymerase chain reaction (JCV-PCR) was negative and brain biopsy was not performed. After a long course of aggressive treatment (several pulsed methylprednisolone infusions, plasmapheresis, intravenous dexamethasone, oral mirtazapine) the patient gradually recovered (EDSS 2.5) and MRI lesions decreased.ConclusionsThis case report demonstrates the importance of monitoring patients carefully after the discontinuation of fingolimod for PML-IRIS and rebound MS with IRIS as these conditions may manifest similarly.

Diagnosis and Management of Fingolimod-Associated Macular Edema.

ObjectiveTo investigate the clinical features, treatment, and prognosis of fingolimod-associated macular edema (FAME) and to provide a reference for its rational management.MethodsFAME-related case reports were included in a pooled analysis by searching Chinese and English databases from 2010 to November 31, 2021.ResultsThe median age of 41 patients was 50 years (range, 21, 67 years), of whom 32 were women. The median time to onset of FAME was 3 m (range.03, 120), and blurred vision (17 cases) and decreased vision (13 cases) were the most common complaints. A total of 55 eyes were involved in FAME, including the left eye (14 cases), right eye (10 cases), and both eyes (15 cases), of which 46 eyes had best-corrected visual acuity close to normal (20/12-20/60) and 8 eyes had moderate to severe visual impairment (20/80-20/500). Fundus examination in 23 patients showed macular edema (11 cases). Optical coherence tomography (OCT) in 39 patients mainly showed perifoveal cysts (24 cases), ME (23 cases), and foveal thickening (19 cases). Fundus fluorescein angiography (FFA) in 18 patients showed vascular leakage (11 cases). Complete resolution of ME occurred in 50 eyes and recovery of visual acuity occurred in 45 eyes at a median time of 2 m (range 0.25, 24) after discontinuation of fingolimod or administration of topical therapy.ConclusionsMacular edema is a known complication of fingolimod. All patients using fingolimod require regular eye exams, especially those with a history of diabetes and uveitis and those undergoing cataract surgery.

Molluscum contagiosum in the setting of Fingolimod: The experience at one institution

Fingolimod treatment has been associated with opportunistic infections, most notably PML and cryptococcal meningitis. There are rare reports of other infections like molluscum contagiosum which are typically associated with impaired cellular immunity as seen in AIDS. Upon review of our multiple sclerosis patient database, we identified eight patients undergoing fingolimod treatment who developed molluscum contagiosum infections. We suspect that this association is a class effect and may also be observed with other S1P receptor modulators. While molluscum contagiosum infection is not life-threatening, it can be extremely distressing for patients, and resolution may require discontinuation of fingolimod.

What happens after fingolimod discontinuation? A multicentre real-life experience.

To analyse the course of multiple sclerosis (MS) after fingolimod withdrawal in a multicentre cohort. Patients who discontinued fingolimod were included. Relapses, Expanded Disability Status Scale (EDSS), and new/gadolinium-enhancing lesions on magnetic resonance imaging (MRI) were assessed during the last year on fingolimod, and in the year after discontinuation. Wilcoxon test was used to analyse the difference in EDSS and relapses between the two periods, and to compare lymphocyte counts at discontinuation and 3months later. Demographic and clinical variables were evaluated using univariable and multivariable logistic regression analyses. Patients were 230 (females 66.1%; mean age 38years; median EDSS 3). Fingolimod was discontinued due to inefficacy in 57%, and 87.4% started another treatment. Relapse was observed in 33% of the patients in the year after discontinuation. Severe reactivation was observed in 15%. During the first 6months after discontinuation, new/enhancing lesions were seen in 62/116 patients. Higher age at the fingolimod discontinuation was found to be associated with a lower probability of inflammatory activity (p = 0.001) and severe reactivation (p = 0.007) during the year after discontinuation. Lower lymphocyte count was a risk factor for clinical, radiological, and severe activity (p = 0.02, p = 0.002, p = 0.01, respectively). The main reason for the discontinuation of fingolimod was inefficacy. One-third of the patients had a relapse during the year after discontinuation, 15% experienced a severe reactivation, and approximately 50% of patients with available MRI scan had new/enhancing lesions. The risk factors for disease activity after discontinuation were low lymphocyte count and younger age.

Lymphocyte recovery after fingolimod discontinuation in patients with MS.

ObjectiveTo investigate the dynamics of immune cells recovery after treatment discontinuation of fingolimod in real-life clinical practice, we analyzed the course of lymphocyte reconstitution and its potential influencing factors in patients with multiple sclerosis (MS).MethodsWe analyzed leukocyte, lymphocyte, and granulocyte counts of 58 patients at 3, 6, and 12 months after fingolimod cessation and the following parameters as potential risk factors for a prolonged lymphopenia up to 12 months: age; sex; Expanded Disability Status Scale, and disease duration at the time of fingolimod start; type and number of previous immunomodulatory treatments; fingolimod treatment duration; lymphocyte count at baseline before fingolimod, at fingolimod stop, and at the time of therapy switch; time interval between fingolimod cessation and new treatment initiation; type of the follow-up immunomodulatory treatment; and corticosteroid administration after fingolimod cessation.ResultsAll patients showed a drop of the lymphocyte count under fingolimod with no relevant leukopenia or neutropenia. One year after discontinuation, still 22% of the patients were lymphopenic and 54% of them did not reach 80% of the baseline lymphocyte value. Low lymphocyte counts before fingolimod start, under fingolimod, and at therapy switch, successive treatment with rituximab, and pretreatment with mitoxantrone were significantly associated with a prolonged immune cell recovery.ConclusionsProlonged lymphopenia after fingolimod cessation exists in a subgroup of patients with MS and should be considered in clinical practice, particularly when changing treatment regimens.

Tumefactive multiple sclerosis in association with fingolimod initiation and discontinuation

Background: Tumefactive multiple sclerosis (TMS) is a rare multiple sclerosis (MS) form that usually manifests as the initial presentation or in the early stages of MS. Objective: The aim of this study is to evaluate reports of TMS associated with fingolimod use. Methods: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the medical literature were searched for cases of TMS occurring during or after fingolimod treatment. Results: We identified 29 TMS cases, 19 following fingolimod initiation and 10 following fingolimod discontinuation. In these cases, a TMS diagnosis occurred at a median of 7 years after MS diagnosis, and a median of 7 and 3 months following initiation and discontinuation of fingolimod, respectively. Twenty-two cases were assessed as possible and seven as probable from a causal association perspective. A much larger crude number of TMS reports was observed for fingolimod compared to other disease-modifying therapies. Conclusion: TMS should be considered when a severe or atypical MS relapse occurs shortly after fingolimod initiation or discontinuation, and should prompt imaging evaluation and appropriate treatment initiation. Prescribers’ awareness of the association between TMS and fingolimod may avoid unnecessary diagnostic procedures. In light of our findings, fingolimod (Gilenya) prescribing information was amended to include TMS in the Warnings and Precautions section.

Fingolimod-associated macular edema controlled with nepafenac non-steroidal anti-inflammatory opthalmologic applications

BackgroundFingolimod, an immunomodulatory agent, is used for the treatment of relapsing–remitting multiple sclerosis (RRMS). Fingolimod-associated macular edema (FAME) is a known complication with an incidence of 0.4%. The current recommendation for treatment of FAME is cessation of fingolimod. There are few case reports with management of FAME with steroid eye drops.Case presentationA 38-year-old Caucasian female patient with history of relapsing–remitting multiple sclerosis (RRMS) and treated with fingolimod developed Fingolimod-associated macular edema (FAME). Nevertheless, FAME was successfully treated with nonsteroidal anti-inflammatory eye drops without discontinuation of fingolimod.ConclusionFAME may be managed with non-steroidal eye drops without discontinuation of fingolimod in appropriate patient monitored with close follow up.

Comparative discontinuation, effectiveness, and switching practices of dimethyl fumarate and fingolimod at 36-month follow-up

BackgroundDimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMTs) for relapsing multiple sclerosis (MS). There are currently no known head-to-head studies comparing DMF and FTY over 36 months, which leaves their relative effectiveness unknown. ObjectiveTo assess real-world discontinuation, effectiveness, and switching practices of DMF and FTY over 36 months along with disease activity after switching DMT. MethodsPatients prescribed DMF (n = 737) and FTY (n = 535) from two academic MS centers were retrospectively reviewed. Discontinuation and effectiveness outcomes were assessed using propensity score (PS) weighting. PS model covariates included sociodemographics and clinical and MRI characteristics. ResultsDiscontinuation was more common in DMF (58.3%) versus FTY (45.2%) over 36 months [OR = 1.81, 95% CI (1.41–2.31), p < .001], largely driven by intolerance [OR = 1.63, 95% CI (1.18–1.73), p < .001]. There were no differences in clinical relapses [OR = 1.27, 95% CI (0.90–1.79), p = .17], gadolinium-enhancing (GdE) lesions [OR = 1.25, 95% CI (0.85–1.84), p = .26], or new T2-hyperintense lesions [OR = 0.99, 95% CI (0.74–1.32), p = .93]. Within 12 months of DMF/FTY discontinuation, switchers to highly effective therapy (HET) versus other DMTs (injectables/orals) had fewer relapses (DMF/HET, 5.9% versus DMF/Other, 14.2%, p = .03; FTY/HET, 11.6% versus FTY/Other, 18.0%, p = .04) and fewer GdE lesions post-FTY (DMF/HET, 10.3% versus DMF/Other, 14.3%, p = .36; FTY/HET, 11.9% versus FTY/Other, 21.5%, p = .04). ConclusionThis combined analysis showed similar effectiveness for DMF and FTY over 36 months with higher DMF discontinuations. Disease activity was lower in switchers to HET versus injectable/oral therapies after DMF/FTY cessation.

Extensive immune reconstitution inflammatory syndrome in Fingolimod-associated PML: a case report with 7 Tesla MRI data

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare complication of patients treated with fingolimod.Case presentationRoutine MRI eventually led to diagnosis of asymptomatic early PML that remained stable after discontinuation of fingolimod. As blood lymphocyte counts normalized, signs of immune reconstitution inflammatory syndrome (IRIS) and renewed MS activity developed. Both, advanced laboratory and ultrahigh field MRI findings elucidated differences between PML and MS.ConclusionsIn our case, early discontinuation of fingolimod yielded a good outcome, lymphocyte counts reflected immune system activity, and paraclinical findings helped to differentiate between PML-IRIS and MS.

Severe Exacerbation of Multiple Sclerosis Following Withdrawal of Fingolimod.

Fingolimod is an effective therapy for multiple sclerosis (MS). Isolated reports of very aggressive MS rebound after discontinuation of fingolimod are drawing neurologists' attention to this potentially severe complication of the drug. Our objective was to collect literature data on cases of MS rebound following fingolimod withdrawal. In addition, we report six new cases of this adverse event in Brazil. We carried out a systematic review of published data on cases of MS rebound after fingolimod was discontinued. In addition, the study reports a retrospective data series of Brazilian patients presenting this rebound reaction. Twenty papers have been published reporting on 52 patients with severe MS rebound after fingolimod withdrawal. Six new patients are included in the present paper, all of them with aggressive rebound and accumulated disability sequelae. We recommend gradual discontinuation of fingolimod with replacement by other treatment. The washout period should not exceed 4weeks.

Discontinuation and Comparative Effectiveness of Dimethyl Fumarate and Fingolimod in Two Large Academic Medical Centers at 36-month Follow-Up (P3.2-065)

Discontinuation and Comparative Effectiveness of Dimethyl Fumarate and Fingolimod in Two Large Academic Medical Centers at 36-month Follow-Up (P3.2-065)

Natalizumab versus fingolimod and dimethyl fumarate in multiple sclerosis treatment.

ObjectiveTo compare 2‐year effectiveness and discontinuation of natalizumab (NTZ) versus fingolimod (FTY) and dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS).MethodsPatients prescribed NTZ, FTY, or DMF at the Rocky Mountain MS Center at University of Colorado were identified. Clinician‐reported data were retrospectively collected. Outcomes include a composite effectiveness measure consisting of new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse, individual effectiveness outcomes and discontinuation over 2 years. Logistic regression was used for data analysis on patients matched by propensity scores and using ATT doubly robust weighting estimator.ResultsA total of 451, 271, and 342 patients were evaluated on NTZ, FTY, and DMF over 2 years, respectively. Patients had a mean age of 39.8 (NTZ), 42.5(FTY), and 45.8 (DMF) years; were predominantly female (76.7% NTZ; 72.0% FTY; 69.6% DMF); and had a mean MS disease duration of 11–12 years for all groups. At ≤24 months, 22.2%, 34.7%, and 33.6% experienced a new T2 lesion, gadolinium‐enhancing lesion, and/or clinical relapse on NTZ, FTY, and DMF, respectively. Using ATT doubly robust weighting estimator, FTY versus NTZ and DMF versus NTZ had an odds ratio of 2.00 (95%CI:[1.41–2.85], P < 0.001) and 2.38 [95% CI: 1.68–3.37], P < 0.001) respectively, for experiencing a new T2 lesion, gadolinium enhancing lesion, and/or clinical relapse. At ≤24 months, 32.6%, 34.3%, and 47.1% discontinued NTZ, FTY, and DMF, respectively. The majority of discontinuations were due to becoming JCV positive(12.6%) for NTZ and due to adverse events for both FTY(17%) and DMF(24.0%).Interpretation NTZ appears to be more effective and tolerable than FTY and DMF.

Discontinuation and comparative effectiveness of dimethyl fumarate and fingolimod in 2 centers.

BackgroundDimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease-modifying therapies for relapsing multiple sclerosis (MS). Observational studies are valuable when randomized clinical trials cannot be done due to ethical or practical reasons. Two-site studies allow investigators to further ascertain external validity of previously examined treatment effect differences. Limited head-to-head 2-site studies exist comparing DMF and FTY.MethodsPatients prescribed DMF (n = 737) and FTY (n = 535) from 2 academic multiple sclerosis (MS) centers (Cleveland Clinic and University of Colorado) were identified. Discontinuation and disease activity endpoints were assessed using propensity score (PS) weighting. Covariates used in the PS model included demographics and clinical and MRI characteristics.ResultsPS weighting demonstrated excellent covariate balance. Discontinuation was more common in DMF (44.2%) compared to FTY (34.8%) over 24 months (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.21–1.99, p < 0.001). The leading cause for discontinuation was intolerability for both DMF (56.1% of DMF discontinuations) and FTY (46.2% of FTY discontinuations) (OR 1.65, 95% CI 1.21–2.25, p = 0.002). The proportion of patients with clinical relapses was low for both medications (DMF, 15.1%; FTY, 13.1%). There was no difference in the proportion of patients with relapses (OR 1.27, 95% CI 0.90–1.80, p = 0.174), gadolinium-enhancing lesions (OR 1.42, 95% CI 0.92–2.20, p = 0.114), or new T2 lesions on brain MRI (OR 1.13, 95% CI 0.83–1.55, p = 0.433).ConclusionsThis combined analysis suggests DMF and FTY have similar effectiveness in a large, 2-site clinical population over 24 months. Discontinuation of both DMTs was common and occurred more frequently with DMF, largely driven by intolerability.

Clinical activity after fingolimod cessation: disease reactivation or rebound?

There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

Comparative Effectiveness and Discontinuation of Dimethyl Fumarate and Fingolimod in Two Large Academic Medical Centers at 24-Month Follow-Up: Sub-Group Analyses (P1.363)

Comparative Effectiveness and Discontinuation of Dimethyl Fumarate and Fingolimod in Two Large Academic Medical Centers at 24-Month Follow-Up: Sub-Group Analyses (P1.363)

A Case of Immune Reconstitution Inflammatory‐like Syndrome in a Patient with Multiple Sclerosis Secondary to Discontinuation of Fingolimod

A Case of Immune Reconstitution Inflammatory‐like Syndrome in a Patient with Multiple Sclerosis Secondary to Discontinuation of Fingolimod

Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis

Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking. To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab. This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county-based community samples of patients with RRMS. Patients with RRMS who received diagnoses from January 1, 2012, to October 31, 2015, who resided in Stockholm or Västerbotten Counties were identified from a Swedish multiple sclerosis registry. All reasons for drug discontinuation of initial treatment choice (main outcome) and specific reasons for switching (secondary outcomes) were analyzed with multivariable Cox regression, including propensity scores. Among 494 patients (median [interquartile range] age, 34.4 [27.4-43.4] years; 158 men [32.0%]), 215 received an injectable DMT (43.5%); 86 (17.4%), dimethyl fumarate; 17 (3.4%), fingolimod; 50 (10.1%), natalizumab; 120 (24.3%), rituximab; and 6 (1.2%), other DMT. Regional preferences were pronounced, with 42 of 52 (81%) and 78 of 442 (18%) receiving rituximab in Västerbotten and Stockholm, respectively. The annual discontinuation rate for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab were 0.03, 0.53, 0.32, 0.38, and 0.29, respectively. Continued disease activity was the main reason for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod; positive John Cunningham virus serology results were the main reason for discontinuation of natalizumab. Rate of clinical relapses and/or neuroradiologic disease activity were significantly lower for rituximab compared with injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates also compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Västerbotten compared with Stockholm (0.09 and 0.37, respectively). Rituximab was superior to all other DMT in terms of drug discontinuation and displayed better clinical efficacy compared with injectable DMTs and dimethyl fumarate with borderline significance compared with natalizumab and fingolimod. The county where rituximab constituted the main initial treatment choice displayed better outcomes in most measured variables. Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS.