Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

BACKGROUND: Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNß-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab. METHODS: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H1 and/or H2 antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion. RESULTS: Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab. CONCLUSION: Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study's prophylaxis regimen.

[The fibroid as clinical problem]. / El mioma como problema clínico.

Uterine fibroids are the most common benign tumours that affect women of reproductive age and they represent the main indication for surgery for benign uterine pathology. In 25% of cases, they become clinically apparent, causing heavy menstrual bleeding, pelvic pain and/or infertility. Therefore, fibroids have a notable impact on the economic costs for the health system and also on the quality of life of the women they afflict. Although MRI is the most precise technique to diagnose fibroids, ultrasound remains the most cost-effective method. Surgery has been the treatment of choice for years, and several minimally invasive procedures have recently been developed. There are a wide variety of conservative medical treatment options, which are continually expanding. Research on the biology of these tumours can lead to new therapeutic options for the management of fibroids as we better understand the role that growth factors and genetic mutations play in them.

El mioma como problema clínico / The fibroid as clinical problem

Los miomas uterinos son los tumores benignos más frecuentes en la mujer en edad reproductiva y constituyen la principal indicación de cirugía por patología uterina benigna. En el 25% de los casos se manifiestan clínicamente, causando sangrado menstrual abundante, dolor pélvico y/o infertilidad. Tienen, por lo tanto, un impacto notable en el coste económico que supone su seguimiento y tratamiento para el sistema sanitario por un lado y, por otro, influyen sustancialmente en la calidad de vida de las mujeres que los padecen. A pesar de que la resonancia magnética es la técnica más precisa para su diagnóstico, la ecografía sigue siendo la técnica de elección por ser la más coste-efectiva. La cirugía ha sido, durante años, el tratamiento de elección. En los últimos años se han desarrollado técnicas quirúrgicas mínimamente invasivas para su tratamiento. Sin embargo hay un amplio abanico de posibilidades terapéuticas conservadoras que, día a día, se va ampliando. La investigación de la biología de estos tumores puede proporcionar nuevas opciones terapéuticas, puesto que conocemos mejor el papel que ejercen los factores de crecimiento y las mutaciones genéticas en ellos (AU)

Uterine fibroids are the most common benign tumours that affect women of reproductive age and they represent the main indication for surgery for benign uterine pathology. In 25% of cases, they become clinically apparent, causing heavy menstrual bleeding, pelvic pain and/or infertility. Therefore, fibroids have a notable impact on the economic costs for the health system and also on the quality of life of the women they afflict. Although MRI is the most precise technique to diagnose fibroids, ultrasound remains the most cost-effective method. Surgery has been the treatment of choice for years, and several minimally invasive procedures have recently been developed. There are a wide variety of conservative medical treatment options, which are continually expanding. Research on the biology of these tumours can lead to new therapeutic options for the management of fibroids as we better understand the role that growth factors and genetic mutations play in them (AU)