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- Alping, P., et al.
(författare)
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Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 950-958
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Tidskriftsartikel (refereegranskat)abstract
- 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%; Umea, 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.
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| 4. |
- 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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| 5. |
- Boremalm, Malin, et al.
(författare)
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Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis
- 2019
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:8, s. 1060-1067
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. Methods Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. Results A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. Conclusions In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
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| 6. |
- Granberg Sandlund, Mikael, et al.
(författare)
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Effectiveness of care in acute dizziness presentations
- 2019
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer. - 0937-4477 .- 1434-4726. ; 276:9, s. 2389-2396
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aims to evaluate whether a management algorithm has improved the effectiveness of care for dizzy patients at Umea University Hospital.Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012-2014) and after (period 2, 2016-2017) the implementation of a management algorithm. Outcomes were changes in a set of pre-defined effectiveness markers and health economic effects.Results: Total n = 2126 and n = 1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% [95% confidence interval (CI) 18.8-23.0%] vs. 37.7% (95% CI 35.2-40.2%), as did BPPV diagnoses, 7.6% (95% CI 6.6-8.8%) vs. 15.3% (95% CI 13.6-17.3%). Hospitalization became less common, 61.5% (95% CI 59.4-63.6%) vs. 47.6% (95% CI 45.1-50.2%). The proportion undergoing any neuroradiological investigation decreased, 44.8% (95% CI 42.7-47.0%) vs. 36.3% (95% CI 33.8-38.7%) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.Conclusions: This study shows that the implementation of a management algorithm for dizzy patients was associated with improved effectiveness of care.
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| 7. |
- Granberg Sandlund, M., et al.
(författare)
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Quality of care in acute dizziness presentations
- 2019
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 26:S1, s. 926-926
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Dizziness is a common symptom at emergency departments. Studies have shown poor quality of care in acute dizziness presentations, including the overuse of computed tomography (CT) and failure to detect benign causes. This study aims to evaluate whether a management algorithm has improved the quality of care for dizzy patients at Umeå University Hospital, Sweden.Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012–2014) and after (period 2, 2016-2017) the implementation of a management algorithm (see figure). Outcomes were changes in a set of pre-defined quality markers and health economic effects.Results: Total n=2126 and n=1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% vs. 37.7%, (p<0.01), as did BPPV diagnoses, 7.6% vs. 15.3%, (p<0.01). Hospitalization became less common, 61.5% vs. 47.6% (p<0.01). The proportion undergoing any neuroradiological investigation decreased, 44.8% vs. 36.3% (p<0.01) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.Conclusion: This study shows how the implementation of a management algorithm for dizzy patients can improve the quality of care and lower the expenses, without an increased number of missed stroke cases.
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| 8. |
- Granqvist, Mathias, et al.
(författare)
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Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking.OBJECTIVE 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.DESIGN, SETTING, AND PATIENTS 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 Vasterbotten Counties were identified from a Swedish multiple sclerosis registry.MAIN OUTCOMES AND MEASURES 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.RESULTS 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 Vasterbotten 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 Vasterbotten compared with Stockholm (0.09 and 0.37, respectively).CONCLUSIONS AND RELEVANCE 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.
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