MANAGEMENT OF ADVERSE REACTIONS TO ALEMTUZUMAB INFUSION

2015 ◽  
Vol 86 (11) ◽  
pp. e4.23-e4 ◽  
Author(s):  
Basil Sharrack ◽  
Lori Mayer ◽  
Alasdair Coles ◽  
Hans-Peter Hartung ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Symptomatic Treatment ◽  
Phase 3 ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE-MS studies of alemtuzumab in patients with relapsing-remitting multiple sclerosis, infusion-associated reactions (IARs) were the most common adverse events. Here we report on IARs during 4-year follow-up. Patients who were treatment-naive (CARE-MS I; NCT00530348) or with inadequate efficacy response to prior therapy (CARE-MS II; NCT00548405) received 2 annual courses of alemtuzumab 12 mg, and as-needed retreatment in an extension study (NCT00930553). Patients received methylprednisolone on the first 3 days of each course. IARs were any adverse event occurring between start of infusion and within 24 hours after end of infusion. 742/811 alemtuzumab-treated patients entered extension. Over 4 years, 70.4% received only 2 initial treatment courses; 22.6% and 6.1% received 3 and 4 courses, respectively. IARs were most frequent in Course 1 (84.7%) versus Courses 2 (68.5%), 3 (65.7%), and 4 (71.1%); frequency decreased on infusion Days 2 and 3 versus Day 1. IARs were predominantly mild to moderate; none led to study withdrawal or death. Serious IAR incidence was 3.1%. Most common IARs were skin disorders (predominantly rash), headache, pyrexia, and nausea. One confirmed anaphylaxis and one non-anaphylactoid hypotension event resolved with treatment. Effective IAR management included premedication, infusion monitoring, symptomatic treatment, and infusion interruption/adjustment.

ALEMTUZUMAB IMPROVES 3-YEAR QUALITY OF LIFE IN CARE-MS II

2015 ◽  
Vol 86 (11) ◽  
pp. e4.9-e4
Author(s):  
Alasdair Coles ◽  
Gavin Giovannoni ◽  
Thibault Moreau ◽  
Eva Havrdova ◽  
David Margolin ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Short Form ◽  
Extension Study ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Emotional Aspects ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE–MS II study (NCT00548405) of relapsing-remitting multiple sclerosis (RRMS) patients with inadequate efficacy response to prior therapy, alemtuzumab demonstrated superior efficacy and quality-of-life (QoL) improvements versus subcutaneous interferon beta-1a, with manageable safety. Here, QoL outcomes are examined in alemtuzumab-treated patients at Year 3 in an ongoing extension study (NCT00930553). 393 of 435 alemtuzumab 12 mg-treated patients entered the extension study; 80 received as-needed alemtuzumab retreatment during Year 3. Mean Functional Assessment of multiple sclerosis total score (scale 0–176) improved from baseline to year 3 (119.1 vs 124.8; P<0.0001), with 5 of 6 subscales significantly improved. Mean Short-Form 36–Item survey physical and mental component summary scores (scale 1–100) rose from baseline to Year 3 (42.7 vs 44.7; P<0.0001, and 44.9 vs 46.5; P=0.042, respectively), with 6 of 8 subscales improved, and 82% and 73% of patients, respectively, having a stable or improved score at Year 3. EuroQol 5–dimensional visual analogue scale score improved from baseline to Year 3 (70.1 vs 73.0; P=0.0045). Overall sustained improvement in physical, mental, and emotional aspects of QoL were observed through 3 years in this population of alemtuzumab-treated RRMS patients, even though most patients received only 2 alemtuzumab treatment courses.

scholarly journals Interferon beta-1b in treatment-naïve paediatric patients with relapsing–remitting multiple sclerosis: Two-year results from the BETAPAEDIC study

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774762 ◽  
Author(s):  
Jutta Gärtner ◽  
Wolfgang Brück ◽  
Almuth Weddige ◽  
Hannah Hummel ◽  
Christiane Norenberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Standard Deviation ◽  
Interferon Beta ◽  
Expanded Disability Status Scale ◽  
Paediatric Patients ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

Background and objective Study evaluating Betaferon(R)'s safety and tolerability in paediatric patients with multiple sclerosis (BETAPAEDIC) is a prospective, open-label observational multicentre study to assess the safety and effectiveness of interferon beta-1b in paediatric patients with relapsing–remitting multiple sclerosis. Methods Treatment-naïve patients (12–16 years) scheduled to start interferon beta-1b were enrolled with follow-up visits every six months for two years. Effectiveness was evaluated by annualised relapse rate, Expanded Disability Status Scale progression, cranial magnetic resonance imaging and cognitive testing. Fatigue was assessed by the Fatigue Severity Scale. Results Sixty-eight patients were screened and 67 enrolled, with mean (standard deviation) age 14.2 (1.3) years ( n=65 in the effectiveness analysis). Mean disease duration was 11 months before study enrolment; at baseline, mean (standard deviation) Expanded Disability Status Scale was 0.6 (1.0); T2 lesion number 18.3 (15.1). Mean annualised relapse rate during the study was 0.7 ( n=57), 28/57 patients (49.1%) had no relapses and for 40/52 (76.9%) no Expanded Disability Status Scale progression was observed; 23/56 (41.1%) were relapse- and progression-free to last follow-up. Neuropsychological test and fatigue scores were within normal ranges (baseline and last follow-up). Eighteen patients had fatigue at some point. New T2 and gadolinium-enhancing (Gd+) lesions were seen in 43/55 (66.2%) and 29/55 (52.7%) patients respectively. Most frequent adverse events were influenza-like illness, headache, injection-site reactions and elevated liver enzymes. Conclusion Interferon beta-1b is an effective treatment with a favourable safety profile for paediatric patients.

Comparison of the EDSS, Timed 25-Foot Walk, and the 9-Hole Peg Test as Clinical Trial Outcomes in Relapsing-Remitting Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012690
Author(s):  
Marcus W. Koch ◽  
Jop P. Mostert ◽  
Jerry S. Wolinsky ◽  
Fred D. Lublin ◽  
Bernard Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Cross Sectional ◽  
Link Type ◽  
Kaplan Meier ◽  
Relapsing Remitting ◽  
Disability Outcome ◽  
Remitting Multiple Sclerosis ◽  
Presentation Methods ◽  
Relapsing Remitting Multiple Sclerosis

Background:Clinical trials in relapsing-remitting multiple sclerosis (RRMS) usually use the Expanded Disability Status Scale (EDSS) as their primary disability outcome measure, while the more recently developed outcomes timed 25 foot walk (T25FW) and nine hole peg test (NHPT) may be more useful and patient-relevant.Objective:To compare the EDSS to the T25FW and NHPT in a large RRMS randomized controlled trial (RCT) dataset.Methods:We used the dataset from CombiRx (clinicaltrials.gov identifier NCT00211887), a large phase 3 RCT, to compare the EDSS to the alternative outcomes T25FW and NHPT. We investigated disability worsening versus similarly defined improvement, unconfirmed versus confirmed and sustained disability change, and the presentation methods cumulative Kaplan-Meier survival curves versus cross-sectional disability worsening.Results:CombiRx included 1,008 participants. A comparison of confirmed versus sustained worsening events showed that throughout the trial, there were substantially fewer sustained than confirmed events, with a positive predictive value of confirmed for sustained worsening at 24 months of 0.73 for the EDSS, 0.73 for the T25FW, and 0.8 for the NHPT. More concerning was the finding that worsening on the EDSS occurred as frequently as similarly defined improvement throughout the three years of follow up, and that improvement rates increased in parallel with worsening rates. The T25FW showed low improvement rates of below 10% throughout the trial. We also found that Kaplan-Meier survival analysis, the standard presentation and analysis method in modern RRMS trials, yields exaggerated estimates of disability worsening. Using the Kaplan-Meier method, the proportion of patients with worsening events steadily increases, until it reaches several fold the number of events seen with more conservative analysis methods. For 3 month CDW at 36 months the ‘Kaplan-Meier’ method yields 2.6 fold higher estimates for the EDSS, 2.9 fold higher estimates for the T25FW and 5.1 fold higher estimates for the NHPT compared to a more conservative presentation of the same data.Discussion:Our analyses raise concerns about using the EDSS as the standard disability outcome in RRMS trials, and suggest that the T25FW may be a more useful measure. These findings are relevant for the design and critical appraisal of RCTs.

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