Interferon β-1a subcutaneously 3 times/week clinical outcome in relapsing multiple sclerosis in Finland

Prognostic factors and long-term treatment response of interferon beta-1a s.c tiw has not been studied in a real-life clinical cohort in Finland. The aim of the paper was to evaluate long-term treatment response, prognostic clinical factors and adherence among interferon beta-1a s.c tiw treated patients in Finland. A retrospective review of medical records was performed. Confirmed relapsing multiple sclerosis patients treated with interferon beta-1a s.c tiw 22 mu g or 44 mu g as their first treatment, from 1996 to 2010 in Western Finland, were included. Longitudinal generalized linear regression models were applied to assess risk of disability progression, using Expanded Disability Status Scale (EDSS), during the treatment period. Odd's ratios with 95% confidence intervals (95% CI) were calculated for risk factors: gender, age at diagnosis, treatment delay, dose, baseline EDSS and EDSS change in one year. Kaplan-Meier was applied to study median time to discontinuation. Mean duration of treatment in 293 cases was 2.9 years (min 0.04, max 13.5). EDSS increase vs. no increase in one-year carried a significant risk for long-term disability progression (1.20, 1.08-1.33). Older age, defined by a 10-year increase in age at diagnosis (1.43, 1.07-1.91) and one-year delay to treatment start showed an increased risk for disability progression (1.05, 0.99-1.11), but gender (0.66, 0.38-1.15) or initial dose (1.00, 0.45-2.25) showed no risk. Treatment was stopped in 37% due to disease activation at median of 1.7 years, and in 25% due to side effects at 9.3 months. Our results show that young age, a short delay to treatment start and slower disability progression were identified as factors for better outcome among cases with interferon beta-1a s.c tiw as their first disease modifying treatment.Peer reviewe

Vaikeahoitoisen migreenin estohoito CGRP-reitin monoklonaalisilla vasta-aineilla

Vertaisarvioitu.Vaikeahoitoisen migreenin estohoidon uusin lääkeryhmä ovat monoklonaaliset vasta-aineet. Näiden biologisten estolääkkeiden vaikutus migreenissä perustuu trigeminovaskulaarisessa järjestelmässä vapautuvan kalsitoniinigeeniin liittyvän peptidin (CGRP) estoon (fremanetsumabi, galkanetsumabi, eptinetsumabi) tai sen reseptorin aktivoitumisen estoon (erenumabi). Valmisteet ovat osoittautuneet tehokkaiksi. Ne ovat hyvin siedettyjä, eikä merkittäviä vasta-aiheita tai yhteisvaikutuksia muiden lääkkeiden kanssa ole todettu. Valmisteiden Kelan erityiskorvattavuuden perusteena on päänsäryn hoitoon perehtyneen lääkärin lausunto, jossa osoitetaan taajaan esiintyvät migreenikohtaukset ja hoitokokeilu vähintään kahdella eri estolääkeryhmän valmisteella. Jatkokorvattavuuden perusteena on migreenitaajuuden puolittuminen. Migreenin biologisten estolääkkeiden pitkäaikaiskäytöstä saadaan tarpeellista kokemusta ja lisätutkimustietoa lähivuosina.Peer reviewe

Vaikeahoitoisen migreenin estohoito CGRP-reitin monoklonaalisilla vasta-aineilla

publishedVersionPeer reviewe

Temporal variability of serum miR-191, miR-223, miR-128, and miR-24 in multiple sclerosis : A 4-year follow-up study

Background: Circulating microRNAs (miRNA) are suggested to be a promising biomarker for multiple sclerosis (MS). Previously, miR-128-3p, miR-24-3p, miR-191-5p and miR-223-3p have been reported to associate with MS pathology. However, their longitudinal changes and association with the disease activity have not been studied. Objectives: To evaluate the serum temporal variability of miR-128-3p, miR-191-5p, miR-24-3p, and miR-223-3p and their association with disability and disease activity in MS. Methods: The expression of four miRNAs in serum was studied in 57 MS patients, 18 clinically isolated syndrome patients, and 32 healthy controls over the four-year follow-up. Results: At the baseline, miR-191-5p was overexpressed in RRMS in comparison to controls, and its levels correlated positively with EDSS and progression index (PI) in RRMS. Increased levels of miR-128-3p were detected in PPMS in comparison to controls, and increased levels correlated with EDSS and PI in RRMS. The expression of miR-24-3p and miR-223-3p did not differ between the subtypes, but miR-223-3p correlated negatively with T1 lesions volumes in SPMS and PPMS. Over the four-years follow-up period, the expression of miR-128-3p and miR-24-3p was stable longitudinally, while temporal changes of miR-191-5p and miR-223-3p were observed in MS. Temporal changes in miR-191-5p were observed to be associated with an increase of EDSS or MRI activity, while the variability of miR-223-3p was associated with relapses. Conclusion: Temporal variability of miR-191-5p and miR-223-3p are associated with changes in disability accumulation and disease activity. While, miR-128-3p was stably expressed and associated with the PPMS subtype and correlated with disability accumulation.publishedVersionPeer reviewe

Cost Assessment Modelling of Treatments for Highly Active Relapsing Multiple Sclerosis

Introduction Cost assessment modelling (CAM) of treatments in highly active relapsing multiple sclerosis was conducted. Methods The CAM was developed using the R programming language. The PICOSTEPS health technology assessment framework was applied in the CAM. Modelled patients were 280 adults with highly active relapsing multiple sclerosis eligible for disease-modifying treatment. Intervention was cladribine tablets, a new and reimbursed oral treatment for highly active relapsing multiple sclerosis in Finland. Comparators included fingolimod, the most used oral reimbursed treatment for the highly active disease, and natalizumab, the most used intravenous treatment, and a treatment mix (80% use fingolimod, 20% use natalizumab) in Finland. Outcomes presented expected annual and cumulative drug-associated costs in the overall population and per patient. Setting was modelled public specialist care in Finland. Time was set to 4 years, without discounting. Effects covered expected drug-associated costs (screening, acquisition, administration, monitoring, adverse events, travelling, productivity). Perspective was a limited societal perspective. Sensitivity analyses regarding all PICOSTEPS components were conducted. Results Cladribine tablets were projected to be cost saving in comparison to fingolimod, natalizumab and treatment mix. The respective modelled savings were euro4,598,742, euro16,249,701 and euro6,928,934 in the overall population, and euro16,424, euro58,035 and euro24,746 per patient, respectively, during the 4 years. The most important cost driver was drug costs, representing 96.3%, 96.0% and 83.4% of modelled costs associated with cladribine tablets, fingolimod and natalizumab, respectively. Cladribine tablets sustained their affordability in the sensitivity analyses. From the perspective of health care payer, cladribine tablets' savings were projected to be euro4,514,509, euro15,145,366 and euro6,640,680 in the overall population, and euro16,123, euro54,091 and euro23,717 per patient in comparison to fingolimod, natalizumab and treatment mix, respectively. Conclusion Based on the CAM, cladribine tablets were projected to robustly save modelled drug-associated costs in comparison to fingolimod, natalizumab and their mix in Finland.Peer reviewe

Miksi MS-tauti yleistyy?

MS-taudin esiintyvyys lisääntyy maailmanlaajuisesti, ja tauti on yleistynyt Suomessakin tasaisesti 1960-luvulta lähtien. Potilaiden eliniän pidentyminen selittää osin esiintyvyyden lisääntymistä, mutta myös taudin ilmaantuvuuden lisääntymisestä Suomessa on havaintoja 30 viime vuoden ajalta. Tätä selittää taudin aiempaa varhaisempi toteaminen diagnostiikan kehittymisen myötä. Myös lääkehoitojen kehitys on korostanut varhaisen diagnoosin merkitystä. Muiden Pohjoismaiden tavoin MS-taudin riski on Suomessa suuri, mutta tutkimusten mukaan sairaus on aina ollut yleisempi Suomen länsi- ja lounaisosissa kuin muualla Suomessa. Esiintyvyyden alueelliset erot liittyvät mahdollisesti eroihin ympäristö- ja perinnöllisyystekijöissä sekä väestörakenteessa, ja niiden tarkempi tutkiminen saattaisi edistää tautimekanismien tuntemusta

Menopausal symptoms and hormone therapy in women with multiple sclerosis : A baseline-controlled study

Background: Depression, sleep disturbances, and cognitive difficulties impair the quality of life in people with multiple sclerosis (MS). Similar symptoms are also frequent during the menopausal transition. In clinical practice, it is important to consider the multifactorial causes of these overlapping symptoms and the potential benefits of menopausal hormone therapy (MHT). The objective of this study was to evaluate vasomotor symptoms (VMS), mood, sleep, and cognition of menopausal women with and without MS at baseline and during one year of MHT. Methods: In this prospective baseline-controlled study, peri- and early postmenopausal participants with (n=14) and without (n=13) MS received MHT containing 1 or 2 mg of estradiol and cyclical 10 mg dydrogesterone for one year. VMS frequency, depressive symptoms (measured by Beck Depression Inventory), insomnia severity (Insomnia Severity Index), and cognitive performance (Paced Auditory Serial Addition Test; PASAT, Symbol Digit Modalities Test; SDMT) were evaluated at baseline and at 3 and 12 months of treatment. Differences in the outcome measures between groups at baseline were assessed using the Mann-Whitney U test. Changes during follow-up compared to baseline within groups were evaluated by Wilcoxon Signed Ranks Test. P < 0.05 was considered for statistical significance. MS activity was monitored by clinical assessment and brain MRI at baseline and at 12 months. Results: Depressive symptoms were more common in MS group, while vasomotor and insomnia symptoms were equally common. During follow-up with MHT, VMS frequency decreased in both groups. Depressive symptoms decreased at 3 months (p = 0.031 with MS; p = 0.024 without MS) and the reduction was sustained at 12 months (p = 0.017; p = 0.042, respectively). Alleviation in insomnia symptoms was seen in participants without MS at 3 months (p = 0.029) and in those participants with MS suffering insomnia at baseline (p = 0.016 at 3 months; p = 0.047 at 12 months). Both groups improved their performance in PASAT, but no significant change was observed in SDMT. MS activity at baseline was mainly stable, and no increase in activity was detected during MHT. Conclusion: Improvements in vasomotor, depressive, and insomnia symptoms observed during one year of MHT are encouraging and suggest that larger placebo-controlled studies of MHT in women with MS are warranted. Cognitive implications were inconclusive because the findings in PASAT likely result from practice effect. MHT did not show any adverse effect on MS activity and increasing safety data will hopefully facilitate patient recruitment for future studies.publishedVersionPeer reviewe

Miksi MS-tauti yleistyy?

MS-taudin esiintyvyys lisääntyy maailmanlaajuisesti, ja tauti on yleistynyt Suomessakin tasaisesti 1960-luvulta lähtien. Potilaiden eliniän pidentyminen selittää osin esiintyvyyden lisääntymistä, mutta myös taudin ilmaantuvuuden lisääntymisestä Suomessa on havaintoja 30 viime vuoden ajalta. Tätä selittää taudin aiempaa varhaisempi toteaminen diagnostiikan kehittymisen myötä. Myös lääkehoitojen kehitys on korostanut varhaisen diagnoosin merkitystä. Muiden Pohjoismaiden tavoin MS-taudin riski on Suomessa suuri, mutta tutkimusten mukaan sairaus on aina ollut yleisempi Suomen länsi- ja lounaisosissa kuin muualla Suomessa. Esiintyvyyden alueelliset erot liittyvät mahdollisesti eroihin ympäristö- ja perinnöllisyystekijöissä sekä väestörakenteessa, ja niiden tarkempi tutkiminen saattaisi edistää tautimekanismien tuntemusta.publishedVersionPeer reviewe