| 1. |
|
|
| 2. |
- Forsberg, L., et al.
(författare)
-
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
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 316-317
-
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.
|
|
| 3. |
|
|
| 4. |
- Kågström, S., et al.
(författare)
-
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
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 763-764
-
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.
|
|
| 5. |
- Ekström, E., et al.
(författare)
-
Real-world longitudinal data of peginterferon beta-1a from the Swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile
- 2021
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 626-627
-
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 disability progression. PegIFN were included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6) due to the importance of studying the long-term safety and effectiveness.Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.Methods: Data was obtained from the Swedish Neuro Registry (NeuroReg). All clinical measures; 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) were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.Results: 393 patients (78% female; 86% RRMS) were included in IMSE 6 between June 2015 and April 2021. Mean age at treatment start was 42 years, mean treatment duration was 23 months. 25% were treatment naïve and 47% switched from other injectables prior PegIFN. The one- and two-year drug survival rate was 58% and 41% respectively, and 31% overall. In total, 271 patients discontinued their PegIFN treatment at some time point, mainly due to adverse events (51%) and lack of effect (26%). Most patients switched to rituximab (37%). During the entire treatment period 54% were relapse-free and 8% had only one relapse (36% missing data). In patients treated at least 24 months tendencies of improve-ments were seen for SDMT and EQ-5D. MSIS-PSYCH showed significantly worsened results (21.2 ± 18.6 to 24.3 ± 19.3, n=46). EDSS, MSSS, MSIS-PHYS and VAS scores remained stable. 25 adverse events (AEs) have been reported to Swedish Medical Product Agency (MPA). 6 of these were classified as serious where general disorders and administration site, and skin (33% respectively) were the most common categories. General disorders and administration site were also the most common for non-serious AEs (68%).Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform. All clinical effectiveness measures, except MSIS-PHYS, remained stable in patients treated for at least 24 months in this nationwide population-based real-world study. Longer follow up is needed to address the long-term effectiveness.
|
|
| 6. |
- Ekström, E., et al.
(författare)
-
The long-term safety and effectiveness of natalizumab (IMSE 1) - Real-world data from a Swedish nationwide pharmaco-epidemiological study
- 2021
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 618-619
-
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. The “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006).Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.Methods: IMSE 1 includes patients starting NTZ treatment. Data is collected from the nationwide Swedish Neuroregistry. Adverse events (AEs), JC-virus status (JCV) and 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) are registered prospectively.Results: 3476 patients (75% female; 81% RRMS) were included from August 2006 until April 2021. Mean age at treatment start was 36 years and mean treatment duration was 51.3 months. 1190 patients were currently treated with NTZ at cut-off and 13% of these were JCV positive (JCV+) with a mean JCV index at 1.07 ± 0.97. 2470 patients (71%) discontinued their NTZ treatment at some time point where the main reason was JCV+ (40%). Most of these patients switched to rituximab (39%). The number of relapses per 1,000 patient years were reduced from 380 before treatment start to 73 during treatment (25% missing data). 61% were relapse-free and 12% had only one relapse during the entire treatment period. All clinical measures showed improvement in mean between baseline and 132 months. Improvements on MSSS, MSIS-29 and SDMT were statistically significant. 117 Serious AEs had been reported to the Swedish Medical Product Agency and included nine cases (2 fatal) of progressive multifocal leukoencephalopathy (PML). Eight of these nine cases had been reported between year 2008 and 2012, and one in 2018. 17 patients died within 6 months of last NTZ infusion. The most common category for non-serious AEs was infections and infestations (21%). For serious AEs neoplasms benign, malignant and unspecified were the most common (16%).Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding clinical cognitive, physical and psychological measures.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Forsberg, L., et al.
(författare)
-
A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)
- 2019
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 316-316
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Teriflunomid (TFM) is a newly approved oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE) in order to track the long-term safety and effectiveness in a real-world setting.Objectives: To track the long-term safety and effectiveness of TFM in a real-world setting.Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 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.Results: A total of 559 TFM-treated patients had been included in the IMSE 4 study from March 2014 to March 2019. 71 % were female and the mean age at treatment start was 46 years. The mean treatment duration was 23 months and 89 % of the patients had RRMS (9 % missing data on MS phenotype). Most patients switched from interferon/glatiramer acetate (36 %) and 16 % of the patients were treatment naïve before starting TFM. The overall one-year drug survival rate was 74 % and the overall two-year drug survival rate was 58 %. 232 (42 %) patients had terminated their treatment at some point, of which 46 % started rituximab treatment and 12 % had no new treatment registered. The most common reasons for discontinuation were AEs (41 %) and lack of effect (39 %). 229 patients had been continuously treated with TFM for ⩾24 months and significant changes in mean baseline values compared to values at 24 months were noted for EDSS (1.9 ± 1.5 to 2.1 ± 1.6, n=66) and SDMT (50.3 ± 10.5 to 52.3 ± 13.0, n=88). A total of 34 AEs were reported to the Swedish Medical Products Agency of which 9 events were classified as serious, none fatal.Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. Patients starting TMF are older at treat-ment start than most other DMTs, which may explain the lack of improvement in EDSS scores. Still, a relatively high proportion switched due to lack of effect. A longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.
|
|
| 10. |
- Forsberg, L., et al.
(författare)
-
A swedish post-market surveillance study : long-term effectiveness and safety of dimethyl fumarate (imse 5) for patients treated at least 36 months: on-demand eposters p0001-p0286
- 2020
-
Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 26:3 Suppl., s. 254-255
-
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).Objectives: 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: 2349 DMF-treated patients were included between March 2014 and June 2020 with an overall drug survival rate of 45%. The main reasons for discontinuation were AEs (50%) and lack of effect (30%). 186 AEs were reported to the Swedish Medical Products Agency, of which 59 were serious. A total of 8 patients have died during DMF treatment or within 6 months of treatment discontinuation. 36 month cohort: 940 patients had con-tinuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 56 months. The majority (50%) had switched from interferon or glatiramer ace-tate, and (24%) were treatment naïve (TN). Significant improve-ments in mean values at 36 months of treatment compared to baseline for the 36-month cohort were noted for MSSS, SDMT, MSIS-29 Psychological, EQ-5D and VAS. When TN patients were solely assessed (n=230) improvements were noted for all above mentioned measures as well as MSIS-29 Psychological. The remaining patients in the cohort; treatment experienced patients (n=710) displayed significant improvements only for MSSS, MSIS-29 Psychological and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 5 months com-pared to 91 months for the remaining cohort. TN were also younger than the remaining cohort (37 years vs 43 years).Conclusions: DMF demonstrates clinical improvements in patients treated 36 months, more pronounced in TN patients. However; due to the high discontinuation rate there is an unavoidable selection bias. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.
|
|
