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- Alping, P., et al.
(author)
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Effectiveness of initial MS treatments in the COMBAT-MS trial : injectables, dimethyl fumarate, natalizumab and rituximab
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 21-22
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Journal article (other academic/artistic)abstract
- Introduction: Direct comparisons across multiple disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) are valuable in clinical decision making. COMBAT-MS (NCT03193866) is an observational drug trial capturing data on clinical relapses, lesions on magnetic resonance imaging (MRI), Expanded Disability Status Scale (EDSS), and drug survival, at all Swedish university clinics.Objective: Compare the effectiveness of the most common initial MS therapies in Sweden.Methods: All first-ever MS treatments with injectables (INJ, interferon-β/glatiramer acetate), dimethyl fumarate (DMF), natalizumab (NTZ), and rituximab (RTX), started 2011-01-01 to 2020-12-14, were identified with prospectively recorded outcome data in the Swedish MS Register. Follow-up continued even if the therapy ended. Missing data were imputed using multiple imputation and potential confounding was adjusted for using stabilized inverse probability of treatment weighting with baseline variables: age, sex, MS duration, geographical region, EDSS, and relapses. All comparisons are made against RTX.Results: We included 1936 first-ever therapy episodes: 856 INJ, 341 DMF, 270 NTZ, and 469 RTX. Baseline characteristics differed by DMT, with natalizumab having the youngest patients, shortest MS duration, and the most previous relapses.After adjustment, the hazard ratio (HR) for first relapse vs RTX was for INJ 5.9 (95% confidence interval 3.7; 9.5), DMF 2.8 (1.7; 4.8), and NTZ 1.8 (1.0; 3.3). Similarly, the relative three-year lesion rate was for INJ 6.06 (3.75; 9.80), DMF 3.52 (2.01; 6.17), and NTZ 2.03 (1.14; 3.64). EDSS differences at three years were only marginally different: INJ 0.25 (0.06; 0.44), DMF 0.05 (-0.16; 0.26), and NTZ 0.00 (-0.23; 0.24). In contrast, HR for treatment discontinuation was marked: INJ 32.5 (19.0; 55.7), DMF 20.2 (11.5; 35.4), and NTZ 16.2 (8.9; 29.5).Conclusions: In treatment-naïve patients, RTX was associated with the lowest risk of relapses and MRI lesions, and by far the lowest probability of switching to a second therapy. In contrast, EDSS at 3 years was similar for RTX, DMF, and NTZ, and only slightly higher for INJ. The apparent difference in effectiveness between NTZ and RTX could possibly be explained by the vulnerable period after switching from NTZ, mainly due to JC virus positivity. These findings underscore the importance of tracking long-term outcomes from first DMT start, while considering subsequent therapy switches.
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| 6. |
- Ekström, E., et al.
(author)
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A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 616-617
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Journal article (other academic/artistic)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 where ALZ was 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 in the nationwide Swedish Neuro Registry (NeuroReg).IMSE 3 includes 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). The Wilcoxon signed-rank test was used to assess changes in effectiveness.Results: 118 patients (59% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2021. Mean age at treatment start was 34 years. At cut-off date 85 patients had been treated with ALZ with at least 48 months of follow-up. Mean values at baseline compared to 48 months showed significant improvements for MSSS and SDMT while EQ-5D, EDSS, MSIS-29 and VAS scores showed tendencies of improvement.The largest proportion of the entire cohort switched from natalizumab (39%) or were treatment naïve (14%) prior ALZ. The number of relapses per 1,000 patient years decreased from 441 before ALZ initiation to 84 during ALZ treatment (16% missing data). 36 adverse events (AEs) were reported to the Swedish Medical Products Agency. 23 were classified as serious and the most common AEs categories were infections and infestations and blood and lymphatic system disorders (23% respectively). For non-serious events endocrine disorders (43%) was the most common category. Two patients died during ALZ treatment, one of which was associated to ALZ treatment, and died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.Conclusions: Patients treated with ALZ for at least 48 months improved or remained stable across all effectiveness measures. Continued follow-up is needed to evaluate the real-world effectiveness and safety of ALZ.
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- Ekström, E., et al.
(author)
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Real-world longitudinal data of peginterferon beta-1a from the Swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 626-627
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Journal article (other academic/artistic)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.
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- Ekström, E., et al.
(author)
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The long-term safety and effectiveness of natalizumab (IMSE 1) - Real-world data from a Swedish nationwide pharmaco-epidemiological study
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 618-619
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Journal article (other academic/artistic)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.
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- Rosengren, V., et al.
(author)
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Clinical effectiveness and safety of cladribine tablets for patients treated at least 12 months in the swedish post-market surveillance study "immunomodulation and multiple sclerosis epidemiology 10" (IMSE 10)
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 623-624
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Journal article (other academic/artistic)abstract
- Background: Cladribine is a deoxyadenosine analogue prodrug that selectively induces immune reconstitution by targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CladT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).Objective: To assess the safety and effectiveness of CladT with focus on patients treated at least 12 months.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), relapses and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and relapse rates were tested using the paired samples T-test.Results: 140 patients were included in the IMSE 10 study since the Swedish market launch in April 2018 with a one year drug survival rate of 96.5%. 6 patients discontinued treatment, of which 2 later restarted. 18 AEs were reported of which 5 were serious. The most common AE reported were infection and infestation (8 reports). 22% of the patients was treated with CladT as their first MS drug. 18% were treated with natalizumab and 11% with dimethyl fumarate prior to CladT.83 patients were treated for at least 12 months. Relapse data was available for 47 of 83 patients in the 12-month cohort. The number of relapses decreased significantly from 249.6 per 1,000 patient years before treatment start to 53.5 during treatment. Only 5 patients in this cohort experienced a relapse during treatment.Significant improvements in mean values at 12 months of treatment compared to baseline were noted for MSSS (p=0.007) and VAS (p=0.029) for the 12-month cohort. All other tests remained stable but significantly unchanged after one year of treatment.Lymphocyte levels decreased from a mean of 1.8 x 109/L at treatment start (n=39) to 1.1 x 109/L after 12 months of treatment (n=37).Conclusions: CladT treatment demonstrates clinical stability in patients treated ⩾ 12 months. However, continued follow-up is needed to assess the effectiveness and safety of CladT over a longer time to assess if these results sustain after the final treatment course has been administered.
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