| 1. |
- Alping, Peter, et al.
(författare)
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Cancer Risk for Fingolimod, Natalizumab, and Rituximab in Multiple Sclerosis Patients
- 2020
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:5, s. 688-699
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Alping, Peter, et al.
(författare)
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Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations
- 2019
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 30:2, s. 230-233
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Bedri, Sahl Khalid, et al.
(författare)
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Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.
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| 4. |
- Breu, Markus, et al.
(författare)
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Rituximab treatment in pediatric-onset multiple sclerosis
- 2024
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Ingår i: EUROPEAN JOURNAL OF NEUROLOGY. - : John Wiley & Sons. - 1351-5101 .- 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Rituximab (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. Methods: In 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. Results: Sixty-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. Conclusion: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.
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| 5. |
- Bronge, Mattias, et al.
(författare)
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Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:17
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-gamma responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4(+) and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.
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| 6. |
- Conradsson, David Moulaee, et al.
(författare)
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Employment status of people with multiple sclerosis in relation to 10-year changes in functioning and perceived impact of the disease
- 2020
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Ingår i: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although it is well known that people with multiple sclerosis (PwMS) retire from work early, little is known about how long-term changes in functioning and perceived impact of multiple sclerosis (MS) interact with sustainability of employment.Objective: To explore changes in functioning and in perceived impact of MS over 10 years, in relation to employment status of PwMS.Methods: In order to measure functioning, data on activities (walking ability, fine hand use, personal activities in daily living); participation in activities of everyday life (domestic, outdoor and leisure activities); body functions (cognitive function, fatigue, depressive symptoms); and perceived impact of MS were collected in 116 PwMS at baseline and at a 10-year follow-up. Ten-year changes were explored with the participants divided into four subgroups based on employment status at the follow-up: 1) full-time work at the 10-year follow-up; 2) part-time work at the 10-year follow-up; 3) declined from working at baseline to not working at the 10-year follow-up; and 4) not working at baseline nor at the 10-year follow-up.Results: Patterns of change in functioning for PwMS who worked showed a more apparent deterioration over 10 years among those working part-time with regard to walking ability, fatigue and depressive symptoms. Members of the subgroups who declined from working at baseline to not working at the 10-year follow-up or who were working neither at baseline nor at the follow-up deteriorated the most in functioning. The subgroup whose employment status declined from baseline to follow-up showed a significant decrease in cognitive function and an increase in perceived physical impact of the disease. All subgroups experienced a deterioration in walking ability over the 10-year span, and in all subgroups a majority had limited fine hand use over the span of the study period.Conclusion: The deterioration in functioning was most apparent in those PwMS whose employment status declined from working at baseline to not working at the 10-year follow-up. Close monitoring of work situation and frequency of activities and participation in everyday activities, as well as recurrent training of functioning, are suggested for maintaining a high level of functioning and work status, or for supporting transition to an appropriate number of working hours.
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| 7. |
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| 8. |
- Englund, Simon, et al.
(författare)
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Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.METHODS: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.RESULTS: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).CONCLUSION: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.
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| 9. |
- Hallberg, Susanna, et al.
(författare)
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Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis : a Swedish cohort study
- 2024
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood.Methods: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated.Results: The mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated.Conclusions: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.
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| 10. |
- Larsson, Veronica, et al.
(författare)
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CLADCOMS- CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 968-969
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report two year prospectively obtained data on the first 100 patients included in the study until April 2021.Objectives/Aims: To investigate number of patients free of disease activity until April 2023 among the first 100 RMS patients included.Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics of Sweden starting Cladribine treatment after 23rd of March 2018. Data was prospectively registered in the Swedish Neuroregistry using highly structured yearly follow-up routines. Descriptive data on relapses, MRI activity, and Patient Reported Outcome Measures from the first 100 patient included in the study were obtained from the registry.Results: By April 2023, 206 patients were included in the CLADCOMS study. In April 2021 the first 100 patients had entered the study including 30% treatment naïve, 26% switched from natalizumab, 10% from dimethyl fumarate and 7% from rituximab. After the first two years after treatment initiation 87% were relapse free. MRI-activity during the first two years after treatment initiation will be analyzed.Analysis of CD19+ B-cells counts over time showed a significant drop from baseline before first dose (0.38x109/L ±0.68) to year one (0.15x109/L ±0.12) and year two (0.13x109/L ±0.09). The proportion of memory B-cells dropped from 11.8% ±9.33% at baseline to 3.0% ±2.8% after the first year and to 2.6% ±2.4% after the second year of treatment. The proportions of naïve B-cells raised over time from 61% ±18.3% at baseline to 76.8% ±18.7 year one and 78.6% ±12.3 after two years of treatment.Conclusion: CladT treatment demonstrates clinical stability during the first two years after treatment initiation. The unique immune depletion helps to explain the durability of effects of Cladribine. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine to investigate time to disease re-activation after full treatment.
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