Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden.
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ABSTRACT:
SUBMITTER: McKay KA
PROVIDER: S-EPMC8637249 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden.
McKay Kyla A KA Piehl Fredrik F Englund Simon S He Anna A Langer-Gould Annette A Hillert Jan J Frisell Thomas T
JAMA network open 20211201 12
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Project description: Not available
| S-EPMC8574640 | biostudies-literature
Project description:We conducted a retrospective cohort study in Kaiser Permanente Southern California from 1 January 2020 to 30 September 2020. We found that rituximab-treated persons with multiple sclerosis (pwMS, n = 1895) were more likely be hospitalized (n = 8, 33.3%), but not die (n = 0) from COVID-19, compared to the 4.81 million non-MS population (5.8% and 1.4%, respectively). Time in months (adjusted OR = 0.32, 95% CI = 0.15-0.69, p = 0.0033) and receiving 1000 mg compared to lower doses at last infusion (adjusted OR = 6.28, 95% CI = 1.38-28.5, p = 0.0173) were independent predictors of COVID-19 severity. Rituximab-treated pwMS should be counseled to take extra precautions in the 5 months following each infusion. Using extended dosing intervals and lower doses could be considered.
| S-EPMC8045943 | biostudies-literature
Project description:ImportanceRituximab and other B-cell-depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear.ObjectivesTo examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2-vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk.Design, setting, and participantsThis retrospective cohort study used Kaiser Permanente Southern California's electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2.ExposuresRituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion.Main outcomes and measuresThe main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record.ResultsAmong 3974 SARS-CoV-2-vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49).Conclusions and relevanceThis cohort study's findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.
| S-EPMC9857265 | biostudies-literature
Project description:Background and purposeRituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.MethodsIn this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed.ResultsSixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38-0.92) to 0.03 (95% CI 0.02-0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70-2.48) to 0.08 (95% CI 0.03-0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30-3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events.ConclusionOur study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.
| S-EPMC11235651 | biostudies-literature
Project description: Not available
| S-EPMC6927430 | biostudies-literature
Project description:Over recent years increased MS incidence, primarily in women, has been reported. We recently reported an unexpectedly high MS prevalence of 189/100,000 in Sweden. In the present study we estimated the nationwide age- and gender-specific MS incidence and the sex ratio in Sweden between 2001 and 2008. MS patients were identified by linking two nationwide health data registers, and the Swedish population register. The earliest registered date of MS diagnosis was determined. By logistic regression, the probability of the date of MS diagnosis being within the incidence period, depending on age and time was estimated for a subset of patients and applied to other patients. By Poisson regression, the hazard functions for the incidence of MS diagnosis were estimated. The expected number of MS patients was 7,361.4. The incidence in the average population of 9,054,658 was 10.2 per 100,000 person-years, and 6.2 and 14.0 per 100,000 person-years for men and women, respectively. The crude female to male ratio was 2.26. No increase of incidence or change of sex ratio was observed from 2001 to 2008. In conclusion, the average MS incidence in Sweden from 2001 to 2008 was 10.2 per 100.000, which was considerably higher than previous regional Swedish estimates of 4.3-6.4. No increase of female to male ratio of MS during the study period was observed. We provide supplementary data that can be used as tools for examining excess MS risk in different study materials.
| S-EPMC4180935 | biostudies-literature
Project description:Multiple sclerosis (MS) is a chronic neurological disease that may cause several different symptoms, some which may entail the need for help in daily life. The aim of this study was to explore the association between sociodemographic background factors and the use of personal assistance and home help services (home help) among persons with MS in Sweden. The study was based on cross-sectional survey data merged with register data and included 3,863 persons with MS aged 20-51. Binary logistic regression analyses were performed to identify factors associated with the use of personal assistance and home help. The central finding of this study was that grade of impairment, as determined by the Expanded Disability Status Scale for Multiple Sclerosis (EDSS), was the most important variable associated with the use of both personal assistance (p < 0.001, OR 18.83) and home help (p < 0.001, OR 6.83). Living alone and receiving sickness benefit were also both associated with the use of personal assistance (p < 0.001, OR 3.32; p 0.001, OR 3.32) and home help (p 0.004, OR 2.56; p 0.011, OR 2.56). Stating a visible symptom of MS as being the most limiting factor of the disease (p 0.001, OR 2.73) and having a disposable income below the limit for poverty risk (p 0.02, OR 2.16) was associated with the use of personal assistance. Receiving informal, meaning unpaid, help (p 0.049, OR 1.89) was associated with the use of home help. Several background factors were controlled for but were not related to differences in the usage of formal help. The results indicated no significant differences in demographic characteristics that could be linked to unequal distribution. However, differences were found between those using personal assistance and home help. The latter were mainly affected by invisible symptoms, suggesting a plausible influencing factor in the chances of obtaining more comprehensive help in the form of personal assistance. Users of home help were also more likely to receive informal help than users of personal assistance, which may suggest that home help is not sufficient.
| S-EPMC10194947 | biostudies-literature
Project description:In the last decades, evidence suggesting the direct or indirect involvement of B cells on multiple sclerosis (MS) pathogenesis has accumulated. The increased amount of data on the efficacy and safety of B-cell-depleting therapies from several studies has suggested the addition of these drugs as treatment options to the current armamentarium of disease modifying therapies (DMTs) for MS. Particularly, rituximab (RTX), a chimeric monoclonal antibody directed at CD20 positive B lymphocytes resulting in cell-mediated apoptosis, has been demonstrated to reduce inflammatory activity, incidence of relapses and new brain lesions on magnetic resonance imaging (MRI) in patients with relapsing-remitting MS (RRMS). Additional evidence also demonstrated that patients with progressive MS (PMS) may benefit from RTX, which also showed to be well tolerated, with acceptable safety risks and favorable cost-effectiveness profile.Despite these encouraging results, RTX is currently approved for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, several forms of vasculitis and rheumatoid arthritis, while it can only be administered off-label for MS treatment. Between Northern European countries exist different rules for using not licensed drug for treating MS. The Sweden MS register reports a high rate (53.5%) of off-label RTX prescriptions in relation to other annually started DMTs to treat MS patients, while Danish and Norwegian neurologists have to use other anti-CD20 drugs, as ocrelizumab, in most of the cases.In this paper, we review the pharmacokinetics, pharmacodynamics, clinical efficacy, safety profile and cost effectiveness aspects of RTX for the treatment of MS. Particularly, with the approval of new anti-CD20 DMTs, the recent worldwide COVID-19 emergency and the possible increased risk of infection with this class of drugs, this review sheds light on the use of RTX as an alternative treatment option for MS management, while commenting the gaps of knowledge regarding this drug.
| S-EPMC7790722 | biostudies-literature
Project description:B cell-depleting therapies such as ocrelizumab (OCR) are highly effective in people with multiple sclerosis (MS). Especially at treatment start and initial infusion, infusion-related reactions (IRR) are a common adverse event. The relevance of acute changes of cell-depleting therapies on peripheral immune compartments and routine lab testing is important for clinical practice. We systematically analyzed routine blood parameters, detailed blood immunophenotyping and serum cytokine profiles in 45 MS patients starting on OCR. Blood samples were collected before and after corticosteroid premedication and directly after each OCR infusion of the first three ocrelizumab infusions. Blood B cells were rapidly depleted and accompanied only by a mild cytokine release at the first OCR infusion. Cytokine release was not significantly detectable from a third application in line with decreasing IRRs. B cell depletion was accompanied by short-lived changes in other immune cell populations in number, activation and cytokine secretion after each OCR infusion. Standard lab parameters did not show any clinically relevant changes. Our data demonstrate only mild changes during the first OCR infusion, which are not present any more during long-term treatment.
| S-EPMC9696175 | biostudies-literature
Project description:This article addresses the concern regarding late-onset dose-limiting toxicities (DLT), moderate toxicities below the threshold of a DLT and cumulative toxicities that may lead to a DLT, which are mostly disregarded or handled in an ad hoc manner when determining the maximum tolerated dose (MTD) in dose-finding cancer clinical trials. An extension of the Time-to-Event Continual Reassessment Method (TITE-CRM) which allows for the specification of toxicity constraints on both DLT and moderate toxicities, and can account for partial information is proposed. The method is illustrated in the context of an Erlotinib dose-finding trial with low DLT rates, but a significant number of moderate toxicities leading to treatment discontinuation in later cycles. Based on simulations, our method performs well at selecting the dose level that satisfies both the DLT and moderate-toxicity constraints. Moreover, it has similar probability of correct selection compared to the TITE-CRM when the true MTD based on DLT only and the true MTD based on grade 2 or higher toxicities alone coincide, but reduces the probability of recommending a dose above the MTD.
| S-EPMC6296314 | biostudies-literature