Progressiivinen multifokaalinen leukoenkefalopatia natalitsumabihoidon komplikaationa

Natalitsumabia käytetään yksinään taudinkulkua muuttavana lääkityksenä erittäin aktiivisen aaltomaisen MS-taudin hoitoon. Natalitsumabihoitoon liittyy riski sairastua progressiiviseen multifokaaliseen leukoenkefalopatiaan (PML). Nykyisin PML-taudin riski natalitsumabihoidon yhteydessä MS-potilailla on 2,77/1 000. Varmistettuja PML-tapauksia natalitsumabihoidon yhteydessä on todettu joulukuuhun 2012 mennessä 312, ja natalitsumabihoitoa on saanut 108 300 MS-potilasta. Suomessa on 350, Ruotsissa 1 871, Norjassa 700 ja Tanskassa 750 natalitsumabihoitoa saavaa MS-potilasta. PML-tapauksia on todettu Suomessa kaksi, Ruotsissa seitsemän, Norjassa yksi ja Tanskassa kolme. Kuvaamme ensimmäisen suomalaisen natalitsumabihoidon komplikaationa PML-tautiin sairastuneen MS-potilaan

MS-taudin diagnoosi, lääkehoito ja kuntoutus

Mitä uutta päivityksessä? MS-taudin lääkehoito aloitetaan heti McDonaldin diagnostisten kriteereiden täytyttyä. Henkilöitä, joilla todetaan kliinisesti eriytynyt oireyhtymä (KEO) ja suurentunut riski saada MS-tauti (MS-tautiin sopivia muutoksia magneettikuvauksissa (MK) ja selkäydinnesteessä), seurataan MK:lla 3-6 kuukauden välein vuoden ajan ensimmäisestä kuvauksesta. Akuutti pahenemisvaihe hoidetaan suonensisäisellä tai suun kautta otettavalla jättiannoksisella kortikosteroidilla. Ensisijainen lääkehoito on beetainterferoni tai glatirameeriasetaatti. Beetainterferonihoidossa olevilta mitataan 12 ja 24 kuukauden kuluttua hoidon aloituksesta MxA-vaste. Jos vaste puuttuu toistetuissa määrityksissä, hoitoa on vaihdettava, ja mikäli vaste on vähäinen, mittaus toistetaan. Beetainterferoni- tai glatirameeriasetaattihoidosta huolimatta aktiivisen MS-taudin toissijainen lääkehoito on natalitsumabi. Immunomoduloiva hoito lopetetaan, mikäli tauti muuttuu toissijaisesti eteneväksi eikä ole enää immunologisesti aktiivinen. English summary: Update on Current Care guidelines: Diagnostics, treatment and rehabilitation of multiple sclerosis Treatment is initiated when the McDonald criteria for relapsing-remitting multiple sclerosis (RRMS) are fulfilled. High-risk patients with clinically isolated syndrome are followed using magnetic resonance imaging for one year after the first imaging. Interferon-β or glatiramer acetate are the first-line immunomodulating drugs (IMD) for RRMS. MxA protein is measured 12 and 24 months after initiation of Interferon-β to evaluate possible development of neutralizing antibodies. If MxA protein may not be detected repeatedly interferon-β treatment is discontinued. If the disease is active in spite of treatment with first-line IMD, natalizumab may be considered as a second-line therapy. IMD is stopped when the transition to secondary progressive phase has occurred (or upon transition to secondary progressive phase)

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Progressiivinen multifokaalinen leukoenkefalopatia natalitsumabihoidon komplikaationa

Natalitsumabia käytetään yksinään taudinkulkua muuttavana lääkityksenä erittäin aktiivisen aaltomaisen MS-taudin hoitoon. Natalitsumabihoitoon liittyy riski sairastua progressiiviseen multifokaaliseen leukoenkefalopatiaan (PML). Nykyisin PML-taudin riski natalitsumabihoidon yhteydessä MS-potilailla on 2,77/1 000. Varmistettuja PML-tapauksia natalitsumabihoidon yhteydessä on todettu joulukuuhun 2012 mennessä 312, ja natalitsumabihoitoa on saanut 108 300 MS-potilasta. Suomessa on 350, Ruotsissa 1 871, Norjassa 700 ja Tanskassa 750 natalitsumabihoitoa saavaa MS-potilasta. PML-tapauksia on todettu Suomessa kaksi, Ruotsissa seitsemän, Norjassa yksi ja Tanskassa kolme. Kuvaamme ensimmäisen suomalaisen natalitsumabihoidon komplikaationa PML-tautiin sairastuneen MS-potilaan

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study

Introduction/Aims Individuals with refractory generalized myasthenia gravis (gMG) who have a history of rituximab use and experience persistent symptoms represent a population with unmet treatment needs. The aim of this analysis was to evaluate the efficacy and safety of eculizumab in patients with refractory anti‐acetylcholine receptor antibody‐positive (AChR+) gMG previously treated with rituximab. Methods This post hoc subgroup analysis of the phase 3 REGAIN study (NCT01997229) and its open‐label extension (OLE; NCT02301624) compared baseline characteristics, safety, and response to eculizumab in participants who had previously received rituximab with those who had not. Rituximab use was not permitted within the 6 months before screening or during REGAIN/OLE. Results Of 125 REGAIN participants, 14 had received rituximab previously (7 received placebo and 7 received eculizumab). In the previous‐rituximab group, 57% had used at least four other immunosuppressants compared with 16% in the no‐previous‐rituximab group. Myasthenia Gravis Activities of Daily Living total scores from eculizumab baseline to week 130 of eculizumab treatment improved in both the previous‐rituximab and no‐previous‐rituximab groups (least‐squares mean −4.4, standard error of the mean [SEM] 1.0 [n = 9] and least‐squares mean −4.6, SEM 0.3 [n = 67], respectively; difference = 0.2, 95% confidence interval −1.88 to 2.22). In addition, in both groups, most patients who were treated with eculizumab for 130 weeks achieved a Myasthenia Gravis Foundation of America post‐intervention status of minimal manifestations (66.7% and 65.0%, respectively). The eculizumab safety profile was similar between groups and consistent with its established profile. Discussion Eculizumab is an effective therapy for patients with refractory AChR+ gMG, irrespective of whether they had received rituximab treatment previously