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- Demirbüker, S. Safer, et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 701-702
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 5” (IMSE 5) in order to monitor and determine the long-term safety and effectiveness in a real-world setting.Objectives: To follow-up the long-term safety and effectiveness of DMF in a real-world setting.Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. The IMSE 5 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve and effectiveness measures were assessed using the Wilcoxon Signed Rank Test.Results: 2010 DMF-treated patients have been included in the IMSE 5 study between March 2014 and April 2018. 73 % were female and the mean age at treatment start was 40.6 years. The mean treatment duration was 22.3 months. 92 % of the patients had RRMS with 2 % missing data on MS phenotype. Most patients switched from interferon and glaimer acetat (41 %) and 24 % of the patients were treatment naïve (13 % were missing data on prior treatment). The overall one year drug survival was 74 % and 889 patients terminated their treatment at some point. Most patients (39 %) switched to rituximab (15 % have no new treatment registered). The most common reason for discontinuation was AEs (53 %) and lack of effect (29 %). 227 (11 %) patients have continued treatment for ≥36 months. In patients treated with DMF continuously for ≥24 months (n=918), significant improvements in mean values at 24 months of treatment compared to mean baseline values have been noted for EDSS (1.9 ± 1.6 to 1.6 ± 1.6, n=196); MSSS (2.5 ± 2.4 to 2.0 ± 2.0, n=145); SDMT (52.6 ± 11.0 to 53.8 ± 11.7, n=315); MSIS-29 Psychological Subscale (26.3 ± 22.8 to 21.8 ± 20.6, n=337); and EQ-5D (0.76 ± 0.23 to 0.81 ± 0.20, n=284).Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to assess the real-world effectiveness and safety of DMF.
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- Forsberg, L., et al.
(författare)
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Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 316-317
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).Objective: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study.Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.Results: 2229 DMF-treated patients were included since March 2014 with a one- and two-year drug survival rate of 73% and 59%. The main reasons for discontinuation were AEs (51%) and lack of effect (29%). 77 AEs were reported to the Swedish Medical Products Agency of which 20 were serious. There were 6 fatal cases of which 4 were confirmed as unrelated to DMF and 2 were still under investigation.865 patients had continuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 44 months. The majority had switched from interferon and glatiramer acetate (IFN&GA) (50%) or were treatment naïve (TN) (22%). Significant improvements in mean values at 36 months of treatment compared to baseline were noted for EDSS, MSSS, SDMT, MSIS-29 Psychological and EQ-5D. When TN patients were solely assessed improvements were noted for EDSS, MSSS, SDMT, MSIS-29 Physical and Psychological and EQ-5D. Treatment experienced patients displayed significant improvements only for MSSS and EQ-5D. Patients previously treated with IFN&GA also improved only in MSSS and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 6 months compared to 83 months for IFN&GA patients and 105 months for the remaining cohort.Conclusions: DMF demonstrates clinical improvements in patients treated ⩾ 36 months, most pronounced in TN patients. However; the tolerability of DMF was reduced since 41% interrupted treatment during the first 24 months of therapy. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.
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- Kågström, S., et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 699-700
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study 1” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).Objective: To follow-up the long-term safety and effectiveness of NTZ in a real-world setting.Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures are registered prospectively.Results: 3052 patients (72% female; 82% RRMS; mean age at treatment start 36 years; mean treatment duration 45.9 months) have been included in IMSE 1 from August 2006 until April 2018. A total of 1234 RRMS patients where included year ≥2011 (JCV test introduction) and had information on JCV (482 anti-JCV anti-bodies (JCV+), 752 JCV negative (JCV-)). 691 of these patients were currently treated with NZT at cutoff date, 88 (13%) of which were JCV+ with a mean JCV index at 1.1±1.1. A total of 612/1234 (49%) discontinued NTZ treatment at some time point of which 266/403 (66%) JCV+ discontinued due to JCV+. JCV- patients mainly discontinued due to pregnancy/planning pregnancy (78/209, 37%) and other reasons (57/209, 27%). The one and two-year drug survival rate was 79% and 45% for JCV+ and 90% and 82% for JCV-. The overall drug survival rate was 16% for JCV+ and 72% for JCV-. In patients with continuous NTZ treatment for ≥2 years (n=738), long lasting stabilization of disease activity was observed. From year 2006 until cutoff, 96 Serious AEs had been reported to the Swedish MPA and included 8 cases (1 fatal) of progressive multifocal leukoencephalopathy (PML), reported between 2008 and 2012. A total of 14 patients have died during or within 6 months after NTZ discontinuation, as reported in NeuroReg. None were reported to be associated to NTZ.Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing long-term data on drug effects and AEs. NTZ is generally well tolerated with sustained effective-ness. The introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a reduced incidence of PML.
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- Kågström, S., et al.
(författare)
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Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1)
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 763-764
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effec-tiveness measures are registered prospectively.Results: A total of 3141 patients were included in the IMSE 1 study from August 2006 until April 2019 (72% female; men age 35 years; 79% RRMS; mean treatment duration 50 months) and 288 had been treated for at least 96 months. 71% of these 288 patients (71% female; men age 37 years; 82% RRMS; mean treatment duration 118 months) were treated with interferons and glatiramer acetate prior NTZ. At some point of time, 31% (90/288) discontin-ued NTZ treatment of which 41% discontinued due to JCV posi-tive (JCV+). In total, 30% (86/288) of these patients were JCV+with a mean JCV index of 1.2±1.0 (6% missing data). Relapses before treatment were reduced from 388/1000 patient years to 54 during treatment, 62% were relapse-free and 17% had 1 relapse during the entire treatment period (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed statistically significant improvement between baseline and 96 months. Over the entire observation time, 104 Serious AEs had been reported to the Swedish MPA and included 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 between 2008 and 2012, and 1in 2018. 16 patients died during or within 6 months of last NTZ infusion. None were judged to be directly associated with NTZ.Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a drastic drop in the incidence of PML.
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- Kågström, S., et al.
(författare)
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Real-world longitudinal data of peginterferon beta-1a from a Swedish national post-marketing surveillance study (IMSE 6) - efficacy and safety profile
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 927-928
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and reduces the tendency to deteriorate disabilities. However, the long-term safety is important, therefore PegINF is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 6” (IMSE 6). Which characterizes the real-world profile of PegIFN, including efficacy, safety, tolerability and patient outcome parameters.Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.Methods: Approximately 60 collaborating neurology clinics continuously recruited PegIFN patients and documented clinical and demographic data in the nationwide Swedish Neuro Registry (NeuroReg). Data were obtained from NeuroReg between June 2015 and April 2018 for the IMSE 6 study.Results: A total of 324 patients (78% female; 88% RRMS; mean age at treatments start 43 years) were followed up to 34 months (mean 15 months) with 26% treatment naïve and 49% switched from other injectables. Mean duration from initial symptom(s) to treatment start was 114 months, and 69 months from MS diagnosis to treatment start. In total, 169 patients discontinued for vari-ous reasons (60% adverse events, 24% lack of effect) and switched mainly to rituximab (63 patients, 37%). The discontinuation rate at 12 months was 42.6%. Relapses before treatment were reduced from 207 to 130/1000 patient years during treatment. With 55% having no relapse and 9% having 1 relapse during treatment period (35% missing data). After 12 months, all clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5-Dimension test (EQ-5D), Visual Analogue Score (VAS), and the mean Symbol Digit Modalities Test (SDMT)) remained stable. A total number of 9 adverse events (6 serious: 1 gastrointestinal disorder, 2 general disorder and administrations site, 2 skin, 1 reproductive) were reported to Swedish Medical Product Agency (MPA).Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. This real-world study presentation from IMSE 6 shows a stable efficacy and safety profile in long-term clinical use.
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