OBJECTIVE: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. METHODS: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. RESULTS: Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0-24 was 0.21 (0.16-0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. CONCLUSIONS: The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered on January 15, 2010.

• MeSH
• daklizumab * škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky MeSH
• imunoglobulin G MeSH
• imunosupresiva * škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH

BACKGROUND: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study. METHODS: An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study. RESULTS: The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%). CONCLUSIONS: The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered January 15, 2010.

• MeSH
• alanintransaminasa účinky léků   MeSH
• analýza podle původního léčebného záměru MeSH
• aspartátaminotransferasy účinky léků   MeSH
• bezpečnost MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunoglobulin G aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• infekce dýchací soustavy chemicky indukované   MeSH
• infekce močového ústrojí chemicky indukované   MeSH
• injekce subkutánní MeSH
• kohortové studie MeSH
• léková dermatitida etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mozek účinky léků   MeSH
• následné studie MeSH
• nazofaryngitida chemicky indukované   MeSH
• pneumonie chemicky indukované   MeSH
• receptor interleukinu-2 - alfa-podjednotka aplikace a dávkování   terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• ulcerózní kolitida chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: In the SELECT trial, disease activity was reduced in patients with multiple sclerosis who received daclizumab high-yield process (HYP) for 52 weeks. The primary aim of the SELECTION extension study was to assess the safety and immunogenicity of extended treatment with daclizumab HYP. METHODS: A multicentre, randomised, double-blind, 52-week extension trial was done in 74 centres in the Czech Republic, Germany, Hungary, India, Poland, Russia, Ukraine, and the UK between Feb 13, 2009, and Oct 3, 2012. Eligible patients were aged 18-55 years, had relapsing-remitting multiple sclerosis, and had completed the SELECT study. Patients who received placebo in SELECT were randomly assigned (1:1) to receive 150 mg or 300 mg subcutaneous daclizumab HYP every 4 weeks for 52 weeks (treatment initiation group); those who had received daclizumab HYP were randomly assigned (1:1) to continue their present dose with (washout and re-initiation group) or without (continuous treatment group) a washout period of 20 weeks. All randomisation was done with a centralised, interactive voice-response system. Patients and personnel were masked to treatment assignment, except for the site pharmacist who prepared the study drug but had no interaction with patients. The primary endpoints were the safety and immunogenicity of daclizumab HYP. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00870740. FINDINGS: 517 (91%) of 567 patients who completed the SELECT trial entered SELECTION, of whom 170 were in the treatment initiation group, 173 in the continuous treatment group, and 174 in the washout and re-initiation group. 11 patients in the treatment initiation group (6%), 13 in the continuous treatment group (8%), and ten in the washout and re-initiation group (6%) had any serious adverse event other than relapse of multiple sclerosis. One patient in the washout and re-initiation group (300 mg daclizumab HYP) died because of autoimmune hepatitis; a contributory role of daclizumab HYP could not be excluded. Seven patients tested positive for neutralising antidrug antibodies: one (1%) of 128 for whom data were available in the continuous treatment group (this patient also tested positive at SELECTION baseline), four (2%) in the treatment initiation group, and two (2%) of 129 in the washout and re-initiation group. INTERPRETATION: Adverse events and immunogenicity were not increased in the second year of continuous treatment with daclizumab HYP or during treatment washout and re-initiation. These results support further assessment of daclizumab HYP for relapsing-remitting multiple sclerosis. FUNDING: Biogen Idec and AbbVie Biotherapeutics.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoglobulin G terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• následné studie MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   patologie   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Daclizumab high-yield process (DAC HYP) is a humanized anti-CD25 monoclonal antibody that inhibits high-affinity interleukin-2 receptor signaling. OBJECTIVE: The objective of this paper is to assess the proportion of DAC HYP- versus placebo-treated patients who were free from disease activity. METHODS: SELECT was a randomized, double-blind, multicenter study of DAC HYP 150 mg or 300 mg, or placebo, administered subcutaneously every four weeks for 52 weeks. In this post-hoc analysis of the SELECT trial, 'disease-activity free' was defined as completion through week 52 without relapses or confirmed three-month disability progression (clinical), with no new/newly enlarging T2-hyperintense lesions and no new gadolinium-enhancing lesions at the week 52 scan (radiological). Primary analyses were based on logistic regression controlling for baseline characteristics. RESULTS: More DAC HYP-treated (39%, n = 156) versus placebo-treated patients (11%, n = 22) were disease-activity free (odds ratio (95% confidence interval), 6.18 (3.71-10.32); p < 0.0001). Furthermore, 77% and 48% of DAC HYP-treated patients were free from clinical or radiological disease activity, respectively, compared with 60% and 18% of placebo-treated patients. CONCLUSION: At one year, DAC HYP resulted in a meaningful increase in the proportion of relapsing-remitting MS patients who were disease-activity free versus placebo.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunoglobulin G terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• progrese nemoci MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Multiple sclerosis (MS) shares many pathologic features with other immune-mediated inflammatory diseases, such as rheumatoid arthritis, Crohn disease, and psoriasis. The development of effective biologic agents for rheumatoid arthritis has resulted in a treatment paradigm shift such that disease remission is now an explicit goal. EXPERT CLINICAL OPINION: The traditional immunomodulatory disease-modifying therapies for MS (interferon beta and glatiramer acetate) delay disease progression and reduce activity on brain MRI to varying degrees; however, they have not been demonstrated to induce disease remission. Therefore, the concept of disease remission or freedom from disease activity in MS has received little attention from the neurology community. We discuss some potential definitions of disease remission in MS and whether freedom from disease activity can become an increasingly useful measure of therapeutic response. FUTURE DIRECTIONS: Future research should be directed at determining the long-term significance of freedom from disease activity during a short-term clinical trial in relapsing-remitting MS.

• MeSH
• antirevmatika terapeutické užití   MeSH
• humanizované monoklonální protilátky MeSH
• imunologické faktory terapeutické užití   MeSH
• indukce remise MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• revmatoidní artritida farmakoterapie   patofyziologie   MeSH
• roztroušená skleróza farmakoterapie   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• znalecký posudek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The efficacy of natalizumab on clinical and radiological measures in the phase III Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study has prompted the investigation of whether natalizumab can increase the proportion of patients with relapsing-remitting multiple sclerosis who do not have disease activity. METHODS: Post-hoc analyses of data from the AFFIRM study were done to determine the effects of natalizumab compared with placebo on the proportion of patients who were free of disease activity over 2 years. Absence of disease activity was defined as no activity on clinical measures (no relapses and no sustained disability progression), radiological measures (no gadolinium-enhancing lesions and no new or enlarging T2-hyperintense lesions on cranial MRI), or a composite of the two. FINDINGS: 383 (64%) of 596 patients taking natalizumab and 117 (39%) of 301 taking placebo were free of clinical disease activity (absolute difference 25.4%, 95% CI 18.7-32.1%, p<0.0001); 342 (58%) of 593 and 42 (14%) of 296 were free of radiological disease activity (43.5%, 37.9-49.1%, p<0.0001); and 220 (37%) of 600 and 22 (7%) of 304 were free of combined activity (29.5%, 24.7-34.3%, p<0.0001) over 2 years. The effect of natalizumab versus placebo was consistent across subgroups of patients with highly active or non-highly active disease at baseline.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• gadolinium diagnostické užití   MeSH
• humanizované monoklonální protilátky MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky terapeutické užití   MeSH
• odds ratio MeSH
• posuzování pracovní neschopnosti MeSH
• přežití po terapii bez příznaků nemoci MeSH
• relabující-remitující roztroušená skleróza patologie   terapie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH