| 1. |
- 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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| 2. |
- Demirbüker, S. Safer, et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 922-923
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Teriflunomid (TFM) 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 4” (IMSE 4) in order to surveille and determine the long-term safety and effectiveness in a real-world setting.Objectives: To follow-up the long-term safety and effectiveness of TFM in a real-world setting.Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. 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: 481 TFM-treated patients have been included in the IMSE 4 study between March 2014 and April 2018. 70 % were female and the mean age at treatment start was 45.8 years. The mean treatment duration was 20.5 months. 89 % of the patients had RRMS with 3 % missing data on MS phenotype. Most patients switched from interferon and glatimer acetat (37 %) and 14 % of the patients were treatment naïve before starting TFM. The overall one year drug survival rate was 81 % and the overall two year drug survival rate was 41 %. 168 (35 %) patients terminated their treatment at some point, of which 33 % started rituximab treatment and 22 % have no new treatment registered. The most common reasons for discontinuation were AEs (49 %) and lack of effect (40 %). 318 patients have been continuously treated with TFM for ≥12 months and mean baseline values compared to val-ues at 12 months have been noted for EDSS (2.0 ± 1.5 to 2.2 ± 1.5, n=141); MSSS (2.6 ± 2.2 to 2.9 ± 2.3, n=126); SDMT (50.8 ± 10.5 to 50.8 ± 10.7, n=165); MSIS-29 Physiological subscale (20.2 ± 19.3 to 19.7 ± 20.0, n=181); MSIS-29 Psychological subscale (28.1 ± 22.2 to 23.7 ± 21.7, n=181); EQ-5D (0.74 ± 0.24 to 0.73 ± 0.26, n=154); and VAS (70.0 ± 20.8 to 70.8 ± 19.6, n=150).Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. However, a longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.
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| 3. |
- Forsberg, L., et al.
(författare)
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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
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 316-316
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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.
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| 4. |
- 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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| 5. |
- Fält, A., et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 706-707
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014).Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting.Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes patients starting ALZ treatment. Adverse events (AEs) and clinical meas-ures; 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 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS) are obtained from NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness.Results: 110 patients (60% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2018. Mean age at treatment start was 34 years and mean treatment duration was 28 months. Most patients (40%) switched from natalizumab and 14% were treatment naïve. 103 patients were currently treated with ALZ at cut-off date and 97 patients had been treated for at least 12 months. Seven patients had discontinued ALZ treatment, of which five patients switched to another disease modifying therapy, one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis and one patient had no treatment registered after ALZ discontinuation. In total, 20 AEs were reported to the Swedish Medical Products Agency; 13 events were classified as non-serious. In patients treated at least 12 months significant improvements were seen for EDSS (2.0±1.4 to 1.6±1.3, n=67), MSSS (3.4±2.6 to 2.6±2.3, n=58), MSIS-29 Physical (22.9±21.0 to 17.5±18.0, n=83), VAS (66.9±22.0 to 73.7±18.5, n=68) and EQ-5D (0.7±0.3 to 0.8±0.3, n=74). MSIS-29 Psychological and SDMT did not improve significantly.Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to evaluate the real-world effectiveness and safety of ALZ.
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| 6. |
- Fält, A., et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)
- 2018
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 24:Suppl. 2, s. 696-697
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Fingolimod (FGL) is an oral therapy for patients with relapsing-remitting multiple sclerosis (RRMS) and the efficacy has been shown in phase II and III studies. However; long-term surveillance and safety is important, therefore FGL is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 2” (IMSE 2).Objective: To follow up the effectiveness and long-term safety of FGL in a real-world setting.Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes data of adverse events (AEs) and 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 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS), obtained from NeuroReg.Results: From September 2011 until April 2018, 1617 patients (67% female; 91% RRMS) were included in IMSE 2. At treatment start 38 patients were ≤20 years (yr), 308 aged 21-30 yr and 1271 aged >30 yr. Mean treatment duration was 34 months. 852 patients were currently treated with FGL at cut-off date and 1230 patients had been treated for at least 12 months. In total, 39% switched treatment from interferons or glatiramer acetate, 26% from natalizumab and 5% from dimethyl fumarate or teriflunomide. 803 patients have discontinued FGL at some point, mainly due to lack of effect (43%) or AEs (34%), most patients switched to rituximab after FGL discontinuation. Relapses were reduced from 281 to 87/1000 patient years (PY) when comparing before and during FGL treatment. In patients aged ≤20 yr, 21-30 yr and >30 yr relapses were reduced from 694 to 144/1000 PY, 455 to 129/1000 PY and 258 to 77/1000 PY, respectively. After 12 months significant improvements were seen in EQ-5D (0.7 to 0.8, n=752), MSSS (3.1 to 2.9, n=410), MSIS-29 Physical (21.1 to 20.0 n=812), MSIS-29 Psychological (29.2 to 24.9, n=812), SDMT (54.3 to 57.0, n=751) and VAS (70.9 to 72.8, n=692). When analysing age groups separately significant improvements were seen in MSSS, SDMT, and MSIS-29 Psychological in patients aged 21-30 yr and >30 yr. EQ-5D, VAS and MSIS-29 Physical significantly improved in patients aged >30 yr.Conclusions: FGL is a generally well-tolerated drug that reduces the clinical activity in MS patients. NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and AEs.
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| 7. |
- Fält, A., et al.
(författare)
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A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 327-328
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Alemtuzumab (ALZ) is an approved disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014).Objective: To track effectiveness and long-term safety of ALZ in a real-world setting.Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; 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 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS).Results: A total of 118 MS patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and April 2019. 95 patients had started ALZ >24 months ago (63% female; 98% RRMS) at cut-off date (31st of Mars 2019), where only 3 patients had switched to another DMT. Mean age at treatment start for patients treated at least 24 months was 34 years and mean treatment duration was 42 months. Mean number of drugs prior ALZ initiation was 2.3. Most patients (41/95) switched to ALZ from natalizumab, while 14/95 patients were treatment naïve with ALZ. The number of relapses per 1,000 patient years decreased from 471 before ALZ initiation to 65 during ALZ treatment (n=83, missing data; n=12). In patients treated ⩾ 24 months significant improvements in mean were seen for EDSS (1.9 ± 1.4 to 1.6 ± 1.3, n=57), MSSS (3.3 ± 2.6 to 2.4 ± 2.1, n=48) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=53), while MSIS-29, SDMT and VAS scores remained stable. A total of 28 adverse events were reported to the Swedish Medical Products Agency, 12 events were classified as serious and 16 events as non-serious. Two patients died during ALZ treatment, of which one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.Conclusions: Patients treated with ALZ for at least 24 months improved or remained stable across all effectiveness measures. Only a very small percentage of patients switched to other DMTs. Continued follow-up is needed to address long term effectiveness and safety of ALZ.
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| 8. |
- Fält, A., et al.
(författare)
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A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 536-537
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) introduced in Sweden 2011. Already from launch FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.Objective: To track the effectiveness and long-term safety of FGL in a real-world setting.Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes patients starting FGL treatment and clinical and demographic data are collected from the NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness measures.Results: From September 2011 until April 2019, 1652 MS patients (67% female; 90% RRMS) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 39 months. 608 patients (64% female; 91% RRMS) had been treated with FGL for at least 48 months with a mean age at treatment start of 40 years and a mean treatment duration of 70 months. A majority (330/608) switched to FGL from interferons/glatiramer acetate, while 194/608 switched from natalizumab. 105/608 patients had discontinued FGL at some point, mainly due to lack of effect (31%) and adverse events (31%). Most patients (57/105) switched to rituximab after FGL discontinuation. The number of relapses per 1,000 patient years were reduced from 275 before FGL initiation to 40 during FGL treatment (27% missing data). In patients treated with FGL at least 48 months significant changes (mean) were seen in Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Visual Analogue Scale (VAS). 80/184 patients had a 4-point or 10% increase in SDMT score between baseline and 48 months. In total 167 adverse events were reported to the Swedish Medical Products Agency of which 77 events were classified as serious.Conclusions: FGL displays a relatively high degree of drug persistence and clinical effectiveness is retained over time with significant improvements in MSSS, SDMT and VAS in patients treated at least 48 months. Furthermore, NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and safety.
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| 9. |
- 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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| 10. |
- 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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