Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies.

BACKGROUND: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses. OBJECTIVE: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) studies and their extensions. METHODS: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course. RESULTS: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses. CONCLUSION: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown.

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

BACKGROUND: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk. OBJECTIVE: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials. METHODS: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion. RESULTS: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials. CONCLUSION: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.

Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis.

BACKGROUND: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. OBJECTIVE: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. METHODS: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. RESULTS: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. CONCLUSION: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.

Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy.

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs). RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined. CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses. CLINICALTRIALSGOV IDENTIFIER: NCT00530348; NCT00930553. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

Clinical outcomes of the REALIZE adjustable gastric band-C at one year in a U.S. population.

BACKGROUND: In 2008, the REALIZE Band (RB) adopted a precurved design (RB-C). The present study is the first multi-institutional report of RB-C outcomes. Our objective was to analyze the 1-year weight loss and safety data from adult RB-C patients treated at multiple U.S. centers (7 typical U.S. bariatric practices, including academic, nonacademic, public, and private practice). METHODS: Patients implanted with the RB-C (preoperative body mass index ≥ 40 kg/m(2) or >35 kg/m(2) with co-morbidity) were recruited. The exclusion criteria included the RB-C label contraindications for use. The outcomes parameters were the percentage of excess weight loss (%EWL), change in body mass index, number and volume of band adjustments, and incidence of complications. RESULTS: Of the 239 patients enrolled in the 2-year study, 158 had 1-year data available for analysis in November 2010. The mean %EWL was 39.2% ± 20.5% (range -7.7 to -116.8, P < .0001). The body mass index decreased from 44.4 ± 5.5 kg/m(2) to 36.4 ± 5.8 kg/m(2) (P < .0001). The variability in the %EWL was significant among the study centers (P < .0001). The average band fill volume at 1 year was 8.0 ± 2.0 mL (range .0-11.1). The total fill volume was >11 mL in 1 patient. No band erosions/migrations, explants, or deaths occurred. CONCLUSION: RB-C appears to be as safe and effective as the first-generation RB. The near 40% EWL at 1 year was consistent with other high-quality publications of the RB. Good weight loss results are achievable, despite the varying postoperative management practices. The low morbidity and the absence of mortality at 12 months reflect positively on the RB-C characteristics. Our findings suggest that the learning curve, related to the postoperative management of the RB-C, might vary by practice and that a greater frequency and smaller band fills might result in better weight loss at 12 months.

Electromagnetic absorption in the head of adults and children due to mobile phone operation close to the head.

The Specific Absorption Rate (SAR) produced by mobile phones in the head of adults and children is simulated using an algorithm based on the Finite Difference Time Domain (FDTD) method. Realistic models of the child and adult head are used. The electromagnetic parameters are fitted to these models. Comparison also are made with the SAR calculated in the children model when using adult human electromagnetic parameters values. Microstrip (or patch) antennas and quarter wavelength monopole antennas are used in the simulations. The frequencies used to feed the antennas are 1850 MHz and 850 MHz. The SAR results are compared with the available international recommendations. It is shown that under similar conditions, the 1g-SAR calculated for children is higher than that for the adults. When using the 10-year old child model, SAR values higher than 60% than those for adults are obtained.