Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.Peer reviewe

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.</p

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Momentum-sijoitusstrategia Suomen osakemarkkinoilla : suoriutuminen aikavälillä 1999–2021

Momentum-ilmiöllä tarkoitetaan osakemarkkinoiden anomaliaa, jonka mukaan historiassa hyvin tuottaneilla osakkeilla on taipumusta jatkaa hyvää kehitystä myös tulevaisuudessa ja huonosti tuottaneilla osakkeilla vastaavasti taipumusta jatkaa huonoa kehitystä. Momentum-ilmiötä koskevissa tutkimuksissa on onnistuttu luomaan ilmiöön perustuvia sijoitusstrategioita osakemarkkinoille. Hyvän sijoitusstrategian tavoitteena on tuottaa markkinoiden keskimääräistä tuottoa paremmin. Tutkijat ovat havainneet momentum-ilmiötä hyödyntävän sijoitusstrategian toimivuuden useilla eri markkinoilla. Tässä tutkielmassa mukaillaan Narasimhan Jegadeesh ja Sheridan Titmanin vuosien 1993 ja 2001 tutkimuksia momentum-ilmiön hyödyntämisestä osakemarkkinoilla. Tutkielmassa muodostetaan 16 momentum-strategiaa eri pituisilla tarkastelu- ja pitoajanjaksoilla. Strategioiden kehitystä tarkastellaan aikavälillä 1999–2021. Valitsemalla edellä mainitulla aikavälillä parhaiten Suomen osakemarkkinoilla suoriutuva momentum-strategia ja tarkastelemalla sitä suhteessa OMX Helsinki Cap-kasvuindeksiin voidaan vastata tutkimusongelmaan. Laadukkaampien tulosten saamiseksi tutkimuksessa tarkastellaan myös momentum-strategian suoriutumista erilaisissa markkinatilanteissa. Tutkimustuloksissa havaittiin yhdeksän kuukauden tarkkailuajalla ja kolmen kuukauden pitoajalla muodostetun momentum-strategian tuottaneen eniten tutkimuksen tarkasteluaikavälillä. Voittaja- ja häviäjäportfolioiden ero tuotoissa oli tilastollisesti merkitsevä, joten momentum-ilmiön esiintymistä Suomen osakemarkkinoilla ei voida kiistää. Parhaiten tuottaneen strategian tarkempi tarkastelu erilaisissa markkinatilanteissa antoi ristiriitaisia tuloksia, eikä niistä voitu tehdä yleistyksiä. Pitkällä aikavälillä momentum-strategia tuotti kumulatiivisesti laskettuna 108,89 % enemmän kuin OMX Helsinki Cap-kasvuindeksi. Momentum-strategian volatiliteetti oli suurempi kuin vertailuindeksillä, mutta sen riskin ja tuoton suhdetta kuvaava Sharpen-luku oli parempi, joten momentum-strategiaa voidaan pitää sijoittajan kannalta parempana valintana kuin OMX Helsinki Cap-kasvuindeksiä