Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: A report from a single Italian center.

BACKGROUND: Alemtuzumab, is a compound approved for highly active MS, and, in Europe, employed after the use of other disease-modifying treatments (DMTs) with an escalation approach or used as a first therapeutic option. The occurrence of secondary autoimmune adverse events and or infections can differ depending on the employed approach. OBJECTIVE: To evaluate the efficacy and safety of alemtuzumab in real-world MS population that encompassed patients previously treated with other DMTs. METHODS: 35 patients, treated with alemtuzumab in a single MS Center, were followed for at least 36 months. The study investigated the prevalence of patients reaching the phase of the non-active disease (NEDA-3). All the adverse events were also reported, and correlations assessed. RESULTS: At the 36-month follow-up, 66,7% of patients achieved the NEDA-3 status, 90,5% of the patients were relapse-free, 85,7% showed no signs of disability progression, nor signs of MRI activity. Adverse events were observed in 45,7% of the patients and ranked as severe in 23% of them. Cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E, and noninfectious meningo-encephalomyelitis were found and reported. For these complications, the post hoc analysis showed possible interactive factors and causality related to previous DMT treatments. CONCLUSIONS: In a real-world MS population like the one investigated in our study, alemtuzumab was found to be an effective treatment when employed as an escalation or rescue therapy. The compound exhibits a variable safety profile and frequent adverse events that are likely depending on previous treatments and their impact on the immune system.

"Nail loss after teriflunomide treatment: A new potential adverse event".

Nail loss might represent a new, reversible, adverse event associated with teriflunomide treatment. It shares close analogies with hair loss and thinning, known adverse events of teriflunomide. MS specialists should be aware of this possibility and evaluate treatment discontinuation.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

CD1A and CD1E gene polymorphisms are associated with susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is thought to be an autoimmune T-cell-mediated disease directed at myelin antigens of the central nervous system. Besides myelin proteins, lipid components of CNS are supposed to play a role as antigens for T cells in MS. CD1 is a family of MHC-like glycoproteins specialized in capturing and presenting a variety of microbial and self lipids and glycolipids to antigen-specific T cells. CD1-restricted T cells specific for gangliosides and sulfatide have been isolated from subjects with MS and in mice with experimental allergic encephalopathy. We genotyped exon 2 of CD1A and CD1E in 205 MS patients and 223 unrelated healthy controls and determined their association with the presence of anti-ganglioside and anti-sulfatide antibodies. CD1E 01-01 is associated with a reduced risk of MS (OR 0.54, p=0.001); CD1A 02-02 (OR 1.99, p=0.012) or CD1E 02-02 (OR 2.45, p=0.000) with an increased risk. The combination of the genotypes CD1A 02-02 and CD1E 02-02 is present in 90.7% of patients but in only 9.4% controls (OR 94.16, p= 0.000). CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to MS. The functional effects of CD1 polymorphisms are unknown, however changes in CD1 alleles may affect numerous immunological functions.

Pregnancy and fetal outcomes after interferon-ß exposure in multiple sclerosis.

OBJECTIVE: To assess pregnancy and fetal outcomes after in utero exposure to interferon-ß (IFNß) in all pregnancies occurring in women with multiple sclerosis (MS) during the study period, with a specific focus on the risk of spontaneous abortion. METHODS: In this cohort study, data were gathered through a standardized, semi-structured interview. Patients who discontinued IFNß less than 4 weeks from conception (exposed) were compared with those who had discontinued the drug at least 4 weeks from conception or who were never treated (not exposed). Possible confounders were handled through multivariate analyses adjusted for propensity score (PS). RESULTS: We collected data on 396 pregnancies in 388 women, 88 classified as exposed (mean exposure 4.6 ± 5.8 weeks). IFNß exposure was not associated with an increased risk of spontaneous abortion (PS-adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.4 to 2.9, p = 0.88), although it was associated with both lower baby weight (PS-adjusted ß -113.8, p < 0.0001) and length (PS-adjusted ß -1.102, p < 0.0001). Proportion of spontaneous abortion in exposed patients fell within the range expected for the Italian population in the same period. IFNß exposure (PS-adjusted OR 2.11, 95% CI 1.18 to 3.78, p = 0.012) and cesarean delivery were the only predictors of preterm delivery. In the exposed group, we did not observe any significant fetal complications, malformations, or developmental abnormalities over a median follow-up of 2.1 years. CONCLUSIONS: Our findings point to the relative safety of IFNß exposure times of up to 4 weeks and can assist neurologists facing therapeutic decisions in women with MS with a pregnancy plan.

Tratamiento ambulatorio de infecciones severas (TAIS). Una nueva modalidad de atención infectológica / Out patient treatment of severe infections. A new modality of patient care

En los últimos años se han desarrollado nuevas modalidades en atención de los pacientes con infecciones severas. Dentro de éstas se encuentran el tratamiento domiciliario y los centros de atención ambulatoria. Desde diciembre de 1995 se ha creado en el Hospital Garrahan un programa denomiando Tratamiento Ambulatorio de Infecciones Severas (TAIS) bajo la segunda modalidad de atención. Durante los primeros 6 meses de trabajo hemos atendido 99 pacientes con infecciones severas. La media de edad fue de 68 meses. La procedencia fue: Gran Buenos Aires 47 pacientes, Capital Federal: 26 e interior: 26 (24 con residencia transitoria en Capital Federal y 2 en Gran Buenos). La media en Km. de distancia al hospital de los pacientes del Gran Buenos Aires fue de 20 Km. El medio de transporte fue el 54,5 por ciento de los pacientes el colectivo, taxi o remise en el 7,1 por ciento, transporte propio en el 24,2 por ciento, transporte de la obra social en 5.1 por ciento y no requirieron transporte 5.1 por ciento. Los diagnósticos más frecuentes fueron: neutropénicos febriles (29 pacientes),infecciones asociadas a catéteres implantables (11), celulitis periorbitarias (8) bacteriemias (8) meningitis bacteriana (6). En el 47 por ciento de las infecciones se documentó el microorganismo responsable. Tenían enfermedad de base el 64.6 por ciento de los pacientes, siendo las leucemias y los tumores sólidos las más comunes. Se obtuvo éxito terapéutico en todos los niños; sólo en 3 se interrumpió el tratamiento ambulatorio por causa no relacionada con la infección tratada. Se ahorraron 374 días/camas, lo que significa una media de liberación de 3.86 camas/días. La implementación de programas como el TAIS es posible y brind amúlples beneficios para el paciente, el hospital y la sociedad.