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BACKGROUND: Alemtuzumab efficacy and safety were established in phase 3 randomized trials. We characterize vital signs during and after the first alemtuzumab infusion course. METHODS: Patients with relapsing-remitting multiple sclerosis commercially prescribed alemtuzumab 12 mg/day on 5 consecutive days (initial course) were enrolled in this prospective, observational study. Preinfusion medications included methylprednisolone, antihistamine, and antipyretics. Primary end point: change from precourse baseline in vital signs during and 2 hours after each alemtuzumab infusion. Secondary end points: infusion duration and serious adverse events (AEs) starting within 24 hours and within 7 days after infusion (AEs collected up to 15 days after treatment). Potentially clinically significant vital sign abnormalities were based on predefined thresholds from literature review. RESULTS: In the 304 patients treated, minimal increases in mean systolic (≤8 mm Hg) and diastolic (≤3 mm Hg) blood pressures from precourse baseline were observed on infusion days 3 to 5. An increase in mean heart rate (20 beats per minute) during the first infusion day normalized by day 2, and smaller increases (5 beats per minute) occurred during subsequent infusions. Serious AEs occurred in two patients (0.7%) during or within 24 hours after infusion and in three patients (1.0%) within 7 days. Mean/median infusion duration was 4 hours. Vital sign abnormalities with potential clinical significance occurred in 62.5% of patients. CONCLUSIONS: Although most patients had potentially clinically significant vital sign abnormalities, mean changes from baseline during and after infusion of the first alemtuzumab course were clinically insignificant. No new safety signals were detected.
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INTRODUCTION: In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were analyzed in patients with or without thyroid AEs (nonserious or serious). A subset of patients with thyroid AEs was analyzed to assess HRQL before and during the onset of thyroid AEs. RESULTS: A total of 811 CARE-MS patients were treated with alemtuzumab. Of these, 342 (42%) patients experienced thyroid AEs over 6 years; serious thyroid AEs occurred in 44 (5%) patients. At year 6, HRQL outcomes generally remained slightly improved or similar to core study baseline in alemtuzumab-treated patients with or without thyroid AEs: FAMS (least-squares mean change from baseline without thyroid AEs, 0.7; with nonserious thyroid AEs, 5.1; with serious thyroid AEs, - 5.3), EQ-5D VAS (2.0; 3.0; - 6.8), SF-36 mental component summary (MCS [0.6; 1.6; - 2.8]), SF-36 physical component summary (PCS [0.8; 1.0; 1.1]). Over 6 years, 63-82% of patients in each group had improved/stable SF-36 MCS and PCS scores. Among patients with thyroid AE onset in year 3 (peak incidence), there were minimal differences between HRQL outcomes before onset (year 2) and after onset (year 3). CONCLUSION: Autoimmune thyroid AEs (serious and nonserious) had minimal impact on HRQL in alemtuzumab-treated patients. These data may aid therapeutic decisions in patients with relapsing MS.
This study looked at alemtuzumab, an approved treatment for multiple sclerosis (MS). People who receive alemtuzumab may develop thyroid problems. The researchers wanted to know whether people who developed thyroid problems with alemtuzumab had a worse quality of life compared with those who did not. The researchers measured quality of life using a questionnaire. The questionnaire looked at people's physical, social, and psychological well-being over 6 years. A total of 811 people with MS treated with alemtuzumab took part in this study. Of these, 469 people (58%) did not develop thyroid problems and 342 people (42%) developed thyroid problems. The thyroid problems were serious in 44 people. The researchers observed that thyroid problems during alemtuzumab treatment did not make quality of life worse in most people. Some people with serious thyroid problems had worsened quality of life; this was mostly among people who required certain treatments for their thyroid problems. Quality of life did not change much in people while the thyroid problems were ongoing. This study shows that thyroid problems after alemtuzumab treatment for MS have little negative impact on quality of life for most people. These findings may help healthcare providers make decisions about MS treatment.