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The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data. [ABSTRACT FROM AUTHOR]

Few controlled trials of disease-modifying therapies (DMTs) have been conducted on the pediatric-onset multiple sclerosis (PoMS) population, leading to extensive off-label use of therapies approved only for adults. This highlights the need for real-world evidence to guide clinical practice. Clinical registries can offer high-quality data, but limitations such as missing and erroneous information must be considered. This validation study compared Swedish Multiple Sclerosis registry data from 122 PoMS patients to medical records. Generally (≥89%), data were confirmed. However, missing data exceeded 30% for rituximab infusions, magnetic resonance imaging, and relapses. Overall, the registry provides valid, real-world data on DMT use in PoMS., (© The Author(s), 2025.)

Objective: To assess comparative effectiveness, safety, and tolerability of off-label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS)., Methods: A Swedish cohort study of persons with relapsing-remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low-dose rituximab was compared with MS-approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale-29 (MSIS-29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention-to-treat approach and were adjusted for demographics, MS features, and health characteristics., Results: We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS-approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS-29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease-modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital-treated infections was higher with rituximab after a therapy switch, but not as a first therapy., Interpretation: This population-based real-world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS-approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024;96:678-693., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA)., Methods: This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity., Results: Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50-2.90 and HR, 1.37; 95% CI, 1.13-1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12-0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing-remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59-2.53), but not in those treated with rituximab., Interpretation: Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing-remitting MS. Infection risk should be considered to improve long term outcomes. ANN NEUROL 2024;96:694-703., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known., Methods: We evaluated the relative cost-effectiveness of rituximab and MS-approved DMTs in a register-based cohort study of Swedish residents with relapsing-remitting MS, aged 18-65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population-based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment-weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS-related clinical characteristics., Results: Off-label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000-$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12-0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost-savings being the price of the index drug itself., Interpretation: The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings. ANN NEUROL 2024;95:1099-1111., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Treatment for multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, has changed drastically in the last 30 years. Several different disease-modifying therapies are now available, with off-label use of the B-cell-depleting antibody rituximab becoming an increasingly popular choice, as more and more studies report on its effectiveness., Objectives: The objective of this study was to summarize the current state of evidence for rituximab as a treatment for relapsing-remitting MS (RRMS)., Methods: A structured literature search was conducted in PubMed, focusing on peer-reviewed studies of adult populations with RRMS. Ongoing trials with rituximab in MS were identified through Clinicaltrials.gov and additional references were identified through review articles., Findings: Despite promising results for rituximab as a treatment of MS, the market-authorization holder switched focus from rituximab and discontinued the industry-sponsored trials programme. However, several observational studies, smaller clinical trials and one large investigator-initiated randomized-controlled trial have continued to report fewer clinical relapses, fewer contrast-enhancing lesions on magnetic resonance imaging and better drug survival with rituximab, compared with MS-approved alternatives., Conclusions: Rituximab should be considered as both a first- and second-line therapy option for most MS patients with active, non-progressive disease. However, as an off-label therapy for MS, regulatory approval remains a barrier for wider adoption in many countries., (© 2023 The Author. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: There is a paucity of information on maternal multiple sclerosis (MS) and risk of adverse pregnancy and perinatal outcomes., Objective: The aim of this study was to determine the association between MS and risks of adverse pregnancy and perinatal outcomes in women with MS. In women with MS, the influence of exposure to disease-modifying therapy (DMT) was also investigated., Methods: Population-based retrospective cohort study on singleton births to mothers with MS and matched MS-free mothers from the general population in Sweden between 2006 and 2020. Women with MS were identified through Swedish health care registries, with MS onset before child's birth., Results: Of 29,568 births included, 3418 births were to 2310 mothers with MS. Compared with MS-free controls, maternal MS was associated with increased risks of elective caesarean sections, instrumental delivery, maternal infection and antepartum haemorrhage/ placental abruption. Compared with offspring of MS-free women, neonates of mothers with MS were at increased risks of medically indicated preterm birth and being born small for gestational age. DMT exposure was not associated with increased risks of malformations., Conclusions: While maternal MS was associated with a small increased risk of few adverse pregnancy and neonatal outcomes, DMT exposure close to pregnancy was not associated with major adverse outcomes.

Objective: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking., Methods: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national health care and census registers. We included 4,187 first-ever initiations of rituximab, 1,620 of fingolimod, and 1,670 of natalizumab in 6,136 MS patients matched for age, sex, and location to 37,801 non-MS general population subjects. Primary outcome was time to first invasive cancer., Results: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate [IR] per 10,000 person-years = 34.4, 95% confidence interval [CI] = 23.7-48.3), fingolimod 28 (IR = 44.0, 95% CI = 29.2-63.5), and natalizumab 17 (IR = 26.0, 95% CI = 15.1-41.6). The general population IR was 31.0 (95% CI = 27.8-34.4). Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population but a possibly higher risk with fingolimod compared to the general population (hazard ratio [HR] = 1.53, 95% CI = 0.98-2.38) and rituximab (HR = 1.68, 95% CI = 1.00-2.84)., Interpretation: In this first large comparative study of 3 highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer, and further studies are warranted to validate these findings. ANN NEUROL 2020;87:688-699., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy., Methods: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umeå, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%)., Results: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center)., Interpretation: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns. Ann Neurol 2016;79:950-958., (© 2016 American Neurological Association.)