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1. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry

Author

Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., Trojano M., Iaffaldano, P, Lucisano, G, Guerra, T, Patti, F, Cocco, E, De Luca, G, Brescia Morra, V, Pozzilli, C, Zaffaroni, M, Ferraro, D, Gasperini, C, Salemi, G, Bergamaschi, R, Lus, G, Inglese, M, Romano, S, Bellantonio, P, Di Monte, E, Maniscalco, G, Conte, A, Lugaresi, A, Vianello, M, Torri Clerici, V, Di Sapio, A, Pesci, I, Granella, F, Totaro, R, Marfia, G, Danni, M, Cavalla, P, Valentino, P, Aguglia, U, Montepietra, S, Ferraro, E, Protti, A, Spitaleri, D, Avolio, C, De Riz, M, Maimone, D, Cavaletti, G, Gazzola, P, Tedeschi, G, Sessa, M, Rovaris, M, Di Palma, F, Gatto, M, Cargnelutti, D, De Robertis̄, F, Logullo, F, Rini, A, Meucci, G, Ardito, B, Banfi, P, Nasuelli, D, Paolicelli, D, Rocca, M, Portaccio, E, Chisari, C, Fenu, G, Onofrj, M, Carotenuto, A, Ruggieri, S, Tortorella, C, Ragonese, P, Nica, M, Amato, M, Filippi, M, Trojano, M, Iaffaldano P., Lucisano G., Guerra T., Patti F., Cocco E., De Luca G., Brescia Morra V., Pozzilli C., Zaffaroni M., Ferraro D., Gasperini C., Salemi G., Bergamaschi R., Lus G., Inglese M., Romano S., Bellantonio P., Di Monte E., Maniscalco G. T., Conte A., Lugaresi A., Vianello M., Torri Clerici V. L. A., Di Sapio A., Pesci I., Granella F., Totaro R., Marfia G. A., Danni M. C., Cavalla P., Valentino P., Aguglia U., Montepietra S., Ferraro E., Protti A., Spitaleri D., Avolio C., De Riz M., Maimone D., Cavaletti G., Gazzola P., Tedeschi G., Sessa M., Rovaris M., Di Palma F., Gatto M., Cargnelutti D., De Robertis̄ F., Logullo F. O., Rini A., Meucci G., Ardito B., Banfi P., Nasuelli D., Paolicelli D., Rocca M. A., Portaccio E., Chisari C. G., Fenu G., Onofrj M., Carotenuto A., Ruggieri S., Tortorella C., Ragonese P., Nica M., Amato M. P., Filippi M., and Trojano M.

Abstract

Background: Active relapsing–remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as “relapsing MS” (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD). Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT’s class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]. Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02–0.37), Natalizumab (0.48, 0.30–0.76), Ocrelizumab (0.1, 0.02–0.45) and Rituximab (0.23, 0.06–0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31–0.59), especially anti-CD20 drugs (0.14, 0.05–0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs. Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch.

Published
2023

2. 138P Activity and efficacy of neoadjuvant chemotherapy (NACT) in luminal-HER2-negative early breast cancer (EBC) according to HER2 score (low vs score 0): A retrospective study

Author

Garufi, G., primary, Carbognin, L., additional, Mastrantoni, L., additional, Maliziola, N., additional, Di Monte, E., additional, Arcuri, G., additional, Frescura, V., additional, Rotondi, A., additional, Fabi, A., additional, Paris, I., additional, Marazzi, F., additional, Franco, A., additional, Mulè, A., additional, Franceschini, G., additional, Orlandi, A., additional, Palazzo, A., additional, Scambia, G., additional, Tortora, G., additional, and Bria, E., additional

Published
2023
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3. 276P Development and external validation of an artificial intelligence (AI)-based machine learning model (ML) for predicting pathological complete response (pCR) in hormone-receptor (HoR)-positive/HER2-negative early breast cancer (EBC) undergoing neoadjuvant chemotherapy (NCT)

Author

Mastrantoni, L., Garufi, G., Di Monte, E., Arcuri, G., Frescura, V., Maliziola, N., Rotondi, A., Giordano, G., Carbognin, L., Fabi, A., Paris, I., Franceschini, G., Orlandi, A., Palazzo, A., Puglisi, F., Dieci, M.V., Milella, M., Scambia, G., Tortora, G., and Bria, E.

Published
2023
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4. 478P Germline BRCA1/2 pathogenetic variants (gBRCA1/2 PV) affect outcome of hormone (HR)-positive HER2-negative metastatic breast cancer (MBC) patients (pts) treated with cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) plus endocrine therapy (ET): The BREAK study

Author

Palazzo, A., Toss, A., Graffeo, R., Fontana, A., Lambertini, M., Pantaleo, F., Perachino, M., Nerone, M., Bianco, N., Vici, P., de Marchis, L., Staropoli, N., Rinaldi, L., Lai, A., Spinelli, G.P., Di Monte, E., Giotta, F., Gennari, A., Cortesi, L., and Bria, E.

Published
2023
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9. Quality of life, depression and fatigue in mildly disabled patients with relapsing–remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study

Author

Patti, F., Lo Fermo, S., Maimone, D., Messina, S., D'Amico, E., Cimino, V., Gasperini, C., Galgani, S., Orefice, V., Brescia Morra, V., Florio, C., Amato, M., Goretti, B., Portaccio, E., Zipoli, V., Bertolotto, A., Bramanti, P., Sessa, E., Centonze, D., Cottone, S., Salemi, G., Falcini, M., Gallo, P., Perini, P., Gigli, G., Giuliani, G., Pucci, S., Grimaldi, L., Murri, L., Lugaresi, A., Monaco, F., Montanari, E., Motti, L., Neri, S., Paciello, M., Provinciali, L., Ragno, M., Rosati, G., Ruggieri, S., Bell'Antonio, P., Tola, M., Caniatti, L., Tonali, P., Batocchi, A., Trojano, M., Di Monte, E., De Caro, M., Ghezzi, A., Zaffaroni, M., Zolo, P., Zorzon, M., Signorino, M., Scarpini, E., Durelli, L., Carolei, A., Todaro, M., Todaro, R., Spitaleri, D., Tartaglione, A., Patti, F, Amato, Mp, Trojano, M, Bastianello, S, Tola, Mr, Picconi, O, Cilia, S, Cottone, S, Centonze, D, Gasperini, C, BRESCIA MORRA, Vincenzo, Lo Fermo, S, Maimone, D, Messina, S, D'Amico, E, Cimino, V, Galgani, S, Orefice, V, Brescia Morra, V, Florio, C, Amato, MP, Goretti, B, Portaccio, E, Zipoli, V, Bertolotto, A, Bramanti, P, Sessa, E, Salemi, G, Falcini, M, Gallo, P, Perini, P, Gigli, GL, Giuliani, G, Pucci, S, Grimaldi, LM, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, S, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Bell'antonio, P, Tola, MR, Caniatti, L, Tonali, P, Batocchi, AP, Di Monte, E, De Caro, MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Signorino, M, Scarpini, E, Durelli, L, Carolei, A, Todaro, M, Todaro, R, Spitaleri, D, Tartaglione, A, Patti F, Amato MP, Trojano M, Bastianello S, Tola MR, Picconi O, Cilia S, Cottone S, Centonze D, Gasperini C, COGIMUS Study Group, and Lugaresi A

Subjects
Adult, Male, Quality of life, Longitudinal study, medicine.medical_specialty, Injections, Subcutaneous, multiple sclerosis, Relapsing-Remitting Multiple Sclerosis, Interferon beta 1a, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Internal medicine, medicine, Humans, Young adult, Fatigue, Depression (differential diagnoses), Aged, Depression, business.industry, Cognitive function, Multiple sclerosis, Cognitive disorder, Interferon beta-1a, Interferon-beta, Middle Aged, medicine.disease, Clinical trial, Neurology, Physical therapy, multiple sclerosis, cognition, interferon beta, Female, Settore MED/26 - Neurologia, Neurology (clinical), Cognition Disorders, business, medicine.drug
Abstract

Background: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. Objective: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. Methods: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing–remitting MS treated with subcutaneous interferon beta-1a. Results: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low ( Conclusion: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.

Published
2011

10. Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study

Author

Patti, F, Amato, Mp, Trojano, M, Bastianello, S, Tola, Mr, Goretti, B, Caniatti, L, DI MONTE, E, Ferrazza, P, BRESCIA MORRA, V, LO FERMO, S, Picconi, O, Luccichenti, G, Vecchio, R, Maimone, D, Messina, S, Gasperini, C, Orefice, V, Florio, C, Portaccio, E, Zipoli, V, Bertolotto, A, Bramant, P, Sessa, E, Centonze, D, Cottone, S, Salemi, G, Falcini, M, Gallo, P, Perini, P, Gigli, Gian Luigi, Giuliani, G, Grimald, Lm, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, S, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Tonali, P, Batocchi, Ap, DE CARO MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Signorino, M, Scarpini, E, Durelli, L, Carolei, A, Todaro, M, Spitaleri, D, Tartaglione, A., Patti, F, Amato, Mp, Trojano, M, Bastianello, S, Tola, Mr, Goretti, B, Caniatti, L, Di Monte, E, Ferrazza, P, BRESCIA MORRA, Vincenzo, Lo Fermo, S, Picconi, O, Luccichenti, G, COGIMUS Study, Group, Vecchio, R, Maimone, D, Messina, S, Gasperini, C, Orefice, V, Brescia Morra, V, Florio, C, Amato, MP, Portaccio, E, Zipoli, V, Bertolotto, A, Bramanti, P, Sessa, E, Centonze, D, Cottone, S, Salemi, G, Falcini, M, Gallo, P, Perini, P, Gigli, GL, Giuliani, G, Grimaldi, LM, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, S, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Tola, MR, Tonali, P, Batocchi, AP, De Caro, MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Signorino, M, Scarpini, E, Durelli, L, Carolei, A, Todaro, M, Spitaleri, D, Tartaglione, A, DI MONTE, E, BRESCIA MORRA, V, LO FERMO, S, and Zorzon, Marino

Subjects
Male, Pediatrics, Intelligence, Relapsing-Remitting, Neuropsychological Tests, Severity of Illness Index, Disability Evaluation, Cognition, Risk Factors, Odds Ratio, Prevalence, Neuropsychological assessment, Prospective Studies, Neurologic Examination, medicine.diagnostic_test, Cognitive impairmet. Cognitive function. Multiple Sclerosis. Neuropsychological assessment, Cognitive disorder, Neuropsychology, Age Factors, Middle Aged, Magnetic Resonance Imaging, Cognitive test, Treatment Outcome, Neurology, Italy, Female, Settore MED/26 - Neurologia, Psychology, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Neurological examination, Risk Assessment, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Predictive Value of Tests, Immunologic Factors, Humans, Interferon-beta, Cognition Disorders, Cross-Sectional Studies, medicine, Expanded Disability Status Scale, Multiple sclerosis, McDonald criteria, medicine.disease, Physical therapy, Neurology (clinical)
Abstract

Background Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing–remitting (RR) MS is unclear. Objectives To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS. Methods Patients aged 18–50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score ≤4.0, who were enrolled in the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study, underwent baseline standardized MRI complete neurological examination and neuropsychological testing. Results A total of 550 patients were enrolled, 327 of whom underwent MRI assessments. Cognitive impairment (impaired performance in ≥3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao’s battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests. Conclusions Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

Published
2009

11. The Italian Multiple Sclerosis Database Network (MSDN): The risk of worsening according to IFNβ exposure in multiple sclerosis

Author

Trojano, M, Russo, P, Fuiani, A, Paolicelli, D, DI MONTE, E, Granieri, Enrico Gavino Giuseppe, Rosati, G, Savettieri, G, Comi, G, Livrea, P, MSDN STUDY GROUP, TROJANO M, RUSSO P, FUIANI A, PAOLICELLI D, DI MONTE E, GRANIERI E, ROSATI G, SAVETTIERI G, COMI G, LIVREA P, MSDN STUDY GROUP, Trojano, M, Russo, P, Fuiani, A, Paolicelli, D, DI MONTE, E, Granirei, E, Rosati, G, Savettieri, G, Comi, Giancarlo, Livrea, P, and MSDN STUDY, Group

Subjects
Adult, Male, Time Factors, computer.software_genre, Central nervous system disease, Cohort Studies, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Adjuvants, Immunologic, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Risk factor, MULTIPLE SCLEROSIS, Demography, Proportional Hazards Models, RISK, Analysis of Variance, Database, business.industry, Proportional hazards model, Multiple sclerosis, Interferon-beta, IFNP, Long term effectiveness, Observational studies, Middle Aged, medicine.disease, Treatment Outcome, Neurology, Databases as Topic, Italy, Propensity score matching, Disease Progression, Regression Analysis, Observational study, Female, Neurology (clinical), Analysis of variance, business, computer, 030217 neurology & neurosurgery, Cohort study
Abstract

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNβ)ina large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44-140 patient-visits with a follow-up of 22-143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNβ for up to 2 years, 39% for 2- 4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR=0.23; 95% CI: 0.17 - 0.30) and worsening of relapse rate (HR=0.19; 95% CI: 0.14 - 0.27) were reduced by about 4- 5- fold in patients exposed to IFNβ for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNβ treatment was lower ( P

Published
2006

12. Subcutaneous interferon β-1a may protect against cognitive impairment in patients with relapsing-remitting multiple sclerosis: 5-year follow-up of the COGIMUS study

Author

Patti, F, Lo, S, Messina, S, Vecchio, R, Maimone, D, Gasperini, C, Orefice, G, Brescia Morra, V, Florio, C, Amato, Mp, Goretti, B, Portaccio, E, Zipoli, V, Bertolotto, A, Bramanti, P, Sessa, E, Centonze, D, Cottone, S, Salemi, G, Falcini, M, Gallo, Paolo, Perini, Paola, Gigli, Gl, Giuliani, G, Grimaldi, Lm, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, G, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Tola, Mr, Caniatti, L, Tonali, P, Batocchi, Ap, Trojano, M, Di Monte, E, De Caro MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Scarpini, E, Durelli, L, Carolei, A, Totaro, R, Spitaleri, D, Tartaglione, A., Patti, F, Lo, S, Messina, S, Vecchio, R, Maimone, D, Gasperini, C, Orefice, G, Brescia-Morra, V, Florio, C, Amato, MP, Goretti, B, Portaccio, E, Zipoli, V, Bertolotto, A, Bramanti, P, Sessa, E, Centonze, D, Cottone, S, Salemi, G, Falcini, M, Gallo, P, Perini, P, Gigli, GL, Giuliani, G, Grimaldi, LM, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, G, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Tola, MR, Caniatti, L, Tonali, P, Batocchi, AP, Trojano, M, Di Monte, E, De Caro, MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Scarpini, E, Durelli, L, Carolei, A, Totaro, R, Spitaleri, D, Tartaglione, A, BRESCIA MORRA, Vincenzo, Amato, Mp, Bastianello, S, Tola, Mr, Plant, A, Orefice, Giuseppe, and G.

Subjects
Adult, Male, medicine.medical_specialty, 5 year follow up, Multiple Sclerosis, Adolescent, Science, Injections, Subcutaneous, Brain damage, Young Adult, Interferon, Recurrence, Internal medicine, medicine, Humans, In patient, Young adult, Cognitive impairment, Sex Characteristics, Multidisciplinary, medicine.diagnostic_test, business.industry, Multiple sclerosis, Multiple Sclerosis, Subcutaneous interferon β-1a, cognitive impairment, Magnetic resonance imaging, Interferon-beta, medicine.disease, Treatment Outcome, Immunology, Medicine, Female, Settore MED/26 - Neurologia, medicine.symptom, Safety, business, Cognition Disorders, Interferon beta-1a, medicine.drug, Research Article, Follow-Up Studies
Abstract

ObjectiveTo assess the effects of subcutaneous (sc) interferon (IFN) -1a on cognition over 5 years in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS).MethodsPatients aged 18-50 years with RRMS (Expanded Disability Status Scale score ≤4.0) who had completed the 3-year COGIMUS study underwent standardized magnetic resonance imaging, neurological examination, and neuropsychological testing at years 4 and 5. Predictors of cognitive impairment at year 5 were identified using multivariate analysis.ResultsOf 331 patients who completed the 3-year COGIMUS study, 265 participated in the 2-year extension study, 201 of whom (75.8%; sc IFN β-1a three times weekly: 44 µg, n = 108; 22 µg, n = 93) completed 5 years' follow-up. The proportion of patients with cognitive impairment in the study population overall remained stable between baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive impairment also remained stable in both treatment groups between baseline and year 5, and between year 3 and year 5. However, a significantly higher proportion of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046). Treatment with the 22 versus 44 µg dose was predictive of cognitive impairment at year 5 (hazard ratio 0.68; 95% confidence interval 0.48-0.97).ConclusionsThis study suggests that sc IFN β-1a dose-dependently stabilizes or delays cognitive impairment over a 5-year period in most patients with mild RRMS. Women seem to be more protected against developing cognitive impairment, which may indicate greater response to therapy or the inherently better prognosis associated with female sex in MS.

Published
2013

13. Changes in magnetic resonance imaging disease measures over 3 years in mildly disabled patients with relapsing-remitting multiple sclerosis receiving interferon β-1a in the COGnitive Impairment in MUltiple Sclerosis (COGIMUS) study

Author

Patti, F., Lo Fermo, S., Vecchio, R., Maimone, D., Messina, S., Gasperini, C., Orefice, V., Brecia Morra, V., Florio, C., Amato, M., Goretti, B., Portaccio, E., Zipoli, V., Bertolotto, A., Bramanti, P., Sessa, E., Centonze, D., Cottone, S., Salemi, G., Falcini, M., Gallo, P., Perini, P., Gigli, G., Giuliani, G., Grimaldi, L., Murri, L., Lugaresi, A., Monaco, F., Montanari, E., Motti, L., Neri, S., Paciello, M., Provinciali, L., Ragno, M., Rosati, G., Ruggieri, S., Tola, M., Caniatti, L., Tonali, P., Batocchi, A., Trojano, M., Di Monte, E., De Caro, M., Ghezzi, A., Zaffaroni, M., Zolo, P., Zorzon, M., Signorino, M., Scarpini, E., Durelli, L., Carolei, A., Totaro, R., Spitaleri, D., Tartaglione, A., Patti F, Lo Fermo S, Vecchio R, Maimone D, Messina S, Gasperini C, Orefice V, Brecia Morra V, Florio C, Amato MP, Goretti B, Portaccio E, Zipoli V, Bertolotto A, Bramanti P, Sessa E, Centonze, D, Cottone, S, Salemi, G, Falcini, M, Gallo, P, Perini, P, Gigli, GL, Giuliani, G, Grimaldi, LM, Murri, L, Lugaresi, A, Monaco, F, Montanari, E, Motti, L, Neri, S, Paciello, M, Provinciali, L, Ragno, M, Rosati, G, Ruggieri, S, Tola, MR, Caniatti, L, Tonali, P, Batocchi, AP, Trojano, M, Di Monte, E, De Caro, MF, Ghezzi, A, Zaffaroni, M, Zolo, P, Zorzon, M, Signorino, M, Scarpini, E, Durelli, L, Carolei, A, Totaro, R, Spitaleri, D, and Tartaglione, A

Subjects
Male, Pathology, Neurology, Disease, Relapsing-Remitting, Neuropsychological Tests, lcsh:RC346-429, 0302 clinical medicine, Relapsing-Remitting Multiple Sclerosi, 030212 general & internal medicine, 10. No inequality, medicine.diagnostic_test, Brain, General Medicine, Magnetic Resonance Imaging, 3. Good health, Female, Settore MED/26 - Neurologia, Radiology, Neurosurgery, Neuroimaging, Immunologic Factors, Dose-Response Relationship, Drug, Humans, Interferon-beta, Quality of Life, Multiple Sclerosis, Relapsing-Remitting, Cognition Disorders, Adult, Drug, Interferon beta-1a, Research Article, medicine.medical_specialty, Multiple Sclerosis, Clinical Neurology, Dose-Response Relationship, 03 medical and health sciences, medicine, Neurochemistry, lcsh:Neurology. Diseases of the nervous system, business.industry, Multiple sclerosis, Magnetic resonance imaging, Brain Magnetic Resonance Imaging, medicine.disease, Clinical trial, Relapsing-Remitting Multiple Sclerosis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background Conventional magnetic resonance imaging (MRI) has improved the diagnosis and monitoring of multiple sclerosis (MS). In clinical trials, MRI has been found to detect treatment effects with greater sensitivity than clinical measures; however, clinical and MRI outcomes tend to correlate poorly. Methods In this observational study, patients (n = 550; 18-50 years; relapsing-remitting MS [Expanded Disability Status Scale score ≤4.0]) receiving interferon (IFN) β-1a therapy (44 or 22 µg subcutaneously [sc] three times weekly [tiw]) underwent standardized MRI, neuropsychological and quality-of-life (QoL) assessments over 3 years. In this post hoc analysis, MRI outcomes and correlations between MRI parameters and clinical and functional outcomes were analysed. Results MRI data over 3 years were available for 164 patients. T2 lesion and T1 gadolinium-enhancing (Gd+) lesion volumes, but not black hole (BH) volumes, decreased significantly from baseline to Year 3 (P < 0.0001). Percentage decreases (baseline to Year 3) were greater with the 44 μg dose than with the 22 μg dose for T2 lesion volume (-10.2% vs -4.5%, P = 0.025) and T1 BH volumes (-7.8% vs +10.3%, P = 0.002). A decrease in T2 lesion volume over 3 years predicted stable QoL over the same time period. Treatment with IFN β-1a, 44 μg sc tiw, predicted an absence of cognitive impairment at Year 3. Conclusion Subcutaneous IFN β-1a significantly decreased MRI measures of disease, with a significant benefit shown for the 44 µg over the 22 µg dose; higher-dose treatment also predicted better cognitive outcomes over 3 years.

Published
2011

14. Serum and CSF N-acetyl aspartate Levels differ in multiple sclerosis and neuromyelitis optica

Author

Edmondo Ceci, Mariangela Mastrapasqua, Anna Maria Simone, Francesco Patti, Emanuele D'Amico, Pietro Iaffaldano, Maria Trojano, Maria Pia Amato, Patrizia Sola, Alessandra Lugaresi, Direnzo, Paolo Livrea, Antonio Frigeri, A. Ghezzi, De Luca G, Maddalena Ruggieri, Bahia Hakiki, Maria Svelto, Di Monte E, Carla Tortorella, Tortorella C, Ruggieri M, Di Monte E, Ceci E, Iaffaldano P, Direnzo V, Mastrapasqua M, Frigeri A, Amato MP, Hakiki B, Ghezzi A, Lugaresi A, De Luca G, Patti F, D'amico E, Sola P, Simone AM, Svelto M, Livrea P, and Trojano M.

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Adolescent, Axonal pathology, Diagnosis, Differential, Multiple Sclerosis, Relapsing-Remitting, immune system diseases, Neuronal damage, mental disorders, medicine, Humans, Aged, Aspartic Acid, Neuromyelitis optica, business.industry, Multiple sclerosis, Neuromyelitis Optica, Middle Aged, Serum samples, N acetyl aspartate, medicine.disease, Response to treatment, nervous system diseases, Psychiatry and Mental health, nervous system, Case-Control Studies, Surgery, Female, multiple sclerosis,neuromyelitis optica, N-acetyl aspartate, CSF, Neurology (clinical), Differential diagnosis, business, Biomarkers
Abstract

Background The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes. Objective To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO. Design Observational, multicentre, prospective, cross sectional study. Methods Serum samples were collected from 48 relapsingeremitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry. Results MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p

Published
2011

15. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a oncognitive decline in mildly disabled patients with relapsing-remitting multiplesclerosis

Author

Patti F, Amato MP, Bastianello S, Caniatti L, Di Monte E, Ferrazza P, Goretti B, Gallo P, BRESCIA MORRA, VINCENZO, Lo Fermo S, Picconi O, Tola MR, Trojano M, COGIMUS S.t.u.d.y.G.r.o.u.p., Patti, F, Amato, Mp, Bastianello, S, Caniatti, L, Di Monte, E, Ferrazza, P, Goretti, B, Gallo, P, BRESCIA MORRA, Vincenzo, Lo Fermo, S, Picconi, O, Tola, Mr, Trojano, M, and Cogimus, S. t. u. d. y. G. r. o. u. p.

Published
2010

16. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis

Author

Patti, F., Lo Fermo, S., Vecchio, R., Maimone, D., Messina, S., Gasperini, C., Orefice, V., Morra, V., Florio, C., Amato, M., Goretti, B., Portaccio, E., Zipoli, V., Bertolotto, A., Bramanti, P., Sessa, E., Centonze, D., Cottone, S., Salemi, G., Falcini, M., Gallo, P., Perini, P., Gigli, G., Giuliani, G., Grimaldi, L., Murri, L., Lugaresi, A., Monaco, F., Montanari, E., Motti, L., Neri, S., Paciello, M., Provinciali, L., Ragno, M., Rosati, G., Ruggieri, S., Tola, M., Caniatti, L., Tonali, P., Batocchi, A., Trojano, M., Di Monte, E., De Caro MF, Ghezzi, A., Zaffaroni, M., Zolo, P., Zorzon, M., Signorino, M., Scarpini, E., Durelli, L., Carolei, A., Todaro, M., Spitaleri, D., Tartaglione, A., Patti F, Amato MP, Bastianello S, Caniatti L, Di Monte E, Ferrazza P, Goretti B, Gallo P, Morra VB, Lo Fermo S, Picconi O, Tola MR, Trojano M, COGIMUS Study Group, Lugaresi A, Vecchio R, Maimone D, Messina S, Gasperini C, Orefice V, Florio C, Portaccio E, Zipoli V, Bertolotto A, Bramanti P, Sessa E, Centonze D, Cottone S, Salemi G, Falcini M, Perini P, Gigli GL, Giuliani G, Grimaldi LM, Murri L, Monaco F, Montanari E, Motti L, Neri S, Paciello M, Provinciali L, Ragno M, Rosati G, Ruggieri S, Tonali P, Batocchi AP, De Caro MF, Ghezzi A, Zaffaroni M, Zolo P, Zorzon M, Signorino M, Scarpini E, Durelli L, Carolei A, Todaro M, Spitaleri D, and Tartaglione A

Subjects
Male, interferon beta-1a, Kaplan-Meier Estimate, Relapsing-Remitting, Neuropsychological Tests, Cohort Studies, Disability Evaluation, Medicine, Adolescent, Young Adult, Middle Aged, Cognition Disorders, Survival Analysis, Female, Dose-Response Relationship, Drug, Humans, Multiple Sclerosis, Relapsing-Remitting, Prospective Studies, Disease Progression, Interferon-beta, Injections, Subcutaneous, Adult, Immunologic Factors, Endpoint Determination, Prospective cohort study, interferon beta, multiple sclerosis, cognitive impairment, Subcutaneous, Cognitive disorder, Hazard ratio, Settore MED/26 - NEUROLOGIA, Neurology, Settore MED/26 - Neurologia, Drug, medicine.drug, medicine.medical_specialty, Multiple Sclerosis, Lower risk, Injections, Dose-Response Relationship, Internal medicine, cognitive function, cognitive impairment, Expanded Disability Status Scale, business.industry, Interferon beta-1a, McDonald criteria, Odds ratio, medicine.disease, Surgery, disability, Neurology (clinical), business, disease progression, multiple sclerosis
Abstract

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNβ-1a) on cognition in mildly disabled patients with relapsing—remitting multiple sclerosis (RRMS). Patients aged 18—50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score ≤4.0) were assigned IFNβ therapy at the physician’s discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNβ-1a (44 mcg: n = 236; 22 mcg: n = 223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480—0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNβ-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNβ-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P = 0.03), although a trend was also seen at the baseline (P = 0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNβ-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26—0.99) compared with the lower dose of IFNβ-1a. These findings suggest that sc IFNβ-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNβ-1a treatment.

Published
2010

17. Real-life impact of early interferon beta therapy in relapsing multiple sclerosis

Author

Trojano, M., Pellegrini, F., Paolicelli, D., Fuiani, A., Zimatore, G., Tortorella, C., Simone, I., Patti, F., Ghezzi, A., Zipoli, V., Rossi, P., Pozzilli, C., Salemi, G., Lugaresi, A., Bergamaschi, R., Millefiorini, E., Clerico, M., Lus, G., Vianello, M., Avolio, C., Cavalla, P., Lepore, V., Livrea, P., Comi, G., Amato, M., Di Monte, E., Iaffaldano, P., Direnzo, V., D'Onghia, M., Lo Fermo, S., Messina, S., D'Amico, E., Rizzo, A., Zaffaroni, M., Portaccio, E., Martinelli, V., Prosperini, L., Onesti, E., Aridon, P., D'Amelio, M., Ragonese, P., De Luca, G., Farina, D., Di Tommaso, V., Tavazzi, E., Bargiggia, V., Crivelli, P., Cortese, A., Di Rezze, S., Durastanti, V., Alfieri, G., Rosellini, I., Modesto, M., Notariello, M., Tortorella, P., Trojano M, Pellegrini F, Paolicelli D, Fuiani A, Zimatore GB, Tortorella C, Simone IL, Patti F, Ghezzi A, Zipoli V, Rossi P, Pozzilli C, Salemi G, Lugaresi A, Bergamaschi R, Millefiorini E, Clerico M, Lus G, Vianello M, Avolio C, Cavalla P, Lepore V, Livrea P, Comi G, Amato MP, Di Monte E, Iaffaldano P, Direnzo V, D'Onghia M, Lo Fermo S, Messina S, D'Amico E, Rizzo A, Zaffaroni M, Portaccio E, Martinelli V, Prosperini L, Onesti E, Aridon P, D'Amelio M, Ragonese P, De Luca G, Farina D, Di Tommaso V, Tavazzi E, Bargiggia V, Crivelli P, Cortese A, Di Rezze S, Durastanti V, Alfieri G, Rosellini I, Modesto M, Notariello M, Tortorella P, Trojano, M, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Zipoli, V, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, Alessandra, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Lepore, V, Livrea, P, Comi, G, and Amato, Mp

Subjects
Adult, Male, Time Factors, Multiple Sclerosis, Interferon beta, Interferon-beta, Cohort Studies, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, observational study, multiple sclerosis, interferon, treatment, early, Sickness Impact Profile, Multiple Sclerosi, Quality of Life, Humans, Female, Settore MED/26 - Neurologia, Prospective Studies, Follow-Up Studies
Abstract

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

Published
2009

19. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

Author

Ernst Wilhelm, Radue, William, H. Stuart, Peter, A. Calabresi, Christian, Confavreux, Steven, L. Galetta, Richard, A. Rudick, Fred, D. Lublin, Bianca, Weinstock Guttman, Daniel, R. Wynn, Elizabeth, Fisher, Athina, Papadopoulou, Frances, Lynn, Michael, A. Panzara, Alfred, W. Sandrock, For, the SENTINEL Investigators including F. Fazekas, Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, D, Lampaert, J., Bartholome, E., Bier, J., Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Finland:, J. Eralinna, Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, Guttman, Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Israel:, O. Abramsky, Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Switzerland:, L. Kappos, Achtnichts, L., Wilmes, S., Turkey:, R. Karabudak, Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni, G., Lim, E. T., Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O'Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O'Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Neurology, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Relapsing-Remitting, Placebo, Antibodies, Monoclonal, Humanized, Gastroenterology, Antibodies, Central nervous system disease, Pharmacotherapy, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, pathology/therapy, Drug Therapy, Internal medicine, Monoclonal, Medicine, Humans, Immunologic Factors, Humanized, medicine.diagnostic_test, business.industry, Multiple sclerosis, Patient Selection, Interferon beta-1a, Antibodies, Monoclonal, Brain, Magnetic resonance imaging, Interferon-beta, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Surgery, Treatment Outcome, Neurology, therapeutic use, Combination, Drug Therapy, Combination, pathology, Female, Neurology (clinical), Adolescent, Adult, Antibodies, Humanized, Antibodies, therapeutic use, Brain, pathology, Drug Therapy, Combination, Female, Humans, Immunologic Factors, therapeutic use, Interferon-beta, therapeutic use, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, pathology/therapy, Patient Selection, Treatment Outcome, business, medicine.drug
Abstract

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone.

Published
2010

20. Real-life impact of early interferonβ therapy in relapsing multiple sclerosis

Author

Trojano, M1, Pellegrini, F, Paolicelli, D, Fuiani, A, Zimatore, Gb, Tortorella, C, Simone, Il, Patti, F, Ghezzi, A, Zipoli, V, Rossi, P, Pozzilli, C, Salemi, G, Lugaresi, A, Bergamaschi, R, Millefiorini, E, Clerico, M, Lus, G, Vianello, M, Avolio, C, Cavalla, P, Lepore, V, Livrea, P, Comi, G, Amato, Mp, Italian Multiple Sclerosis Database Network (MSDN) Group, Di Monte, E, Iaffaldano, P, Direnzo, V, D'Onghia, M, Lo Fermo, S, Messina, S, D'Amico, E, Rizzo, A, Zaffaroni, M, Portaccio, E, Martinelli, V, Prosperini, L, Onesti, E, Aridon, P, D'Amelio, M, Ragonese, P, De Luca, G, Farina, D, Di Tommaso, V, Tavazzi, E, Bargiggia, V, Crivelli, P, Cortese, A, Di Rezze, S, Durastanti, V, Alfieri, G Rosellini I, Modesto, M, Notariello, M, and Tortorella, P.

Published
2009

23. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Affirm, Investigators, Fazekas, SENTINEL Investigators including: F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher, A., Rothenfusser Körber, E., Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky D. Karusiss, O. Abramsky D. Karusiss, Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fern ez Fern ez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, L., Achtnichts, L., Wilmes, S., Karabudak, R., Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni ET Lim, G. Giovannoni E. T. Lim, Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss V. Gupta, M. Reiss V. Gupta, Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel A. Babu, A. Perel A. Babu, Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor S. Humphries, P. Fodor S. Humphries, Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., S. M, El, Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Kaiser, J. Javerbaum, Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo R. Kishner, B. Steingo R. Kishner, Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan M. Yerby, S. Cohan M. Yerby, Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., KoD Gelber C. Fortin, M. K. o. D. Gelber C. Fortin, Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, J., Nicholas, A., Slaughter, R., Archer, R., Harik, S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Ch ler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., R. T, On, Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Ari, D. B, Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair EW Radue, M. S. i. n. c. l. a. i. r. E. W. Radue, de Vera, A., Bacelar, O., Kuster, P., and Kappos, L. .

Subjects
medicine.medical_specialty, Multiple Sclerosis, Enzyme-Linked Immunosorbent Assay, Relapsing-Remitting, Antibodies, Monoclonal, Humanized, Gastroenterology, Antibodies, law.invention, Disability Evaluation, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, Double-Blind Method, law, Antibody Specificity, Internal medicine, Monoclonal, medicine, Secondary Prevention, Humans, Adverse effect, Antibodies, Blocking, Humanized, Antibodies, Monoclonal, Brain, Flow Cytometry, Interferon-beta, Magnetic Resonance Imaging, Placebo Effect, Treatment Outcome, Neuroscience (all), Expanded Disability Status Scale, business.industry, Multiple sclerosis, Incidence (epidemiology), Interferon beta-1a, medicine.disease, Blocking, Multiple sclerosis functional composite, Immunology, Neurology (clinical), business, medicine.drug
Abstract

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.

Published
2007

24. Health-related quality of life in multiple sclerosis: Effects of natalizumab

Author

Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, : S., Grupe, A., Gutmann, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky, : O., Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, : C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Kragt, J. J., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Visual analogue scale, Health Status, Population, Pain, Comorbidity, Placebo, Antibodies, law.invention, Natalizumab, Randomized controlled trial, Quality of life, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, Monoclonal, medicine, Prevalence, Humans, Longitudinal Studies, education, Humanized, education.field_of_study, Expanded Disability Status Scale, Neuroscience (all), business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Female, Patient Satisfaction, Treatment Outcome, United States, Quality of Life, Multiple sclerosis, medicine.disease, Neurology, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Published
2007

27. The incidence and significance of anti-natalizumab antibodies. Results from the AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Fazekas, The following investigators participated in the SENTINEL study: F., Enzinger, * C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, * E., Egg, R., Deisenhammer, F., Lampaert, D. Decoo* J., Bier, E. Bartholome* J., Stenager, Denmark: E., Rasmussen, * M., Binzer, M., Ravnborg, M., Soelberg Sørensen, * P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, * E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, * J., Soilu Hänninen, M., Reunanen, M., Remes, * A., Keskinarkaus, I., Moreau, T., Noblet, * M., Rouaud, O., Couvreur, G., Edan, G., Lepage, * E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Gout, O., Deschamps, * R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, * J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittion Vouyouvitch, * S., Lacour, J. C., Pelletier, J., Feuillet, * L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, * K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, * D., Renouil Guy, N., Cesaro, P., Degos, * F., Benisty, S., Decavel, L. Rumbach* P., Confavreux, C., Blanc, * S., Aubertin, P., Riche, G., Brochet, B., Ouallet, * J. C., Anne, O., Menck, S., Grupe, * A., Guttman, E., Lensch, E., Fucik, * E., Heitmann, S., Hartung, H. P., Schröter, * M., Kurz, F. M. W., Heidenreich, F., Trebst, * C., Pul, R., Hohlfeld, R., Krumbholz, * M., Pellkofer, H., Haas, J., Segert, * A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, * K., Hoffmann, V., Zettl, U., Steinhagen, * V., Adler, S., Steinbrecher, A., Rothenfusser Körber, * E., Zellner, R., Baum, K., Günther, * A., Bläsing, H., Stoll, G., Gold, * R., Bayas, * A., Kleinschnitz, C., Limmroth, V., Katsarava, * Z., Kastrup, O., Haller, P., Stoeve, * S., Höbel, D., Oschmann, P., Voigt, * K., Burger, C. V., Karusiss, O. Abramsky* D., Achiron, A., Kishner, * I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, * D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, Paolo, Ranzato, * F., Tiberio, M., Perini, P., Laroni, A., Marrosu, M., Marchi, * E. Cocco P., Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, * A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, G., Pizzorno, * M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, * V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, * M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, * E., Tacken, H., Frequin, S. T. F. M., Siegers, * H. P., Mauser, H. W., Fernandez Fernandez, O., León, * A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, * C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, * L., Moral, E., Martinez, S., Kappos, L., Achtnichts, * L., Wilmes, S., Karabudak, R., Kurne, * A., Erdem, S., Siva, A., Saip, * S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, * F., Topcular, B., Lim, G. Giovannoni* E. T., Lava, N., Murnane, * M., Dentinger, M., Zimmerman, E., Gupta, M. Reiss* V., Scott, T., Brillman, * J., Kunschner, L., Wright, D., Babu, A. Perel* A., Rivera, V., Killian, * J., Hutton, G., Lai, E., Picone, Bernard W. M., Cadivid, * D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, * A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, * P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, * M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, * C., Tyler, R., Horvit, A., Humphries, P. Fodor* S., Wynn, D., Nagar, * C., O’Brien, D., Allen, N., Turel, A., Friedenberg, * S., Carlson, J., Hosey, J., Crayton, H., Richert, * J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, * Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, * C., Rorick, M., Reed, R., Elias, S., Feit, * H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, * K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, * C., Fleck, J., Horak, H., Javerbaum, J., Elmore, * R., Garcia, E., Tasch, E., Gruener, G., Celesia, * G., Chawla, J., Miller, A., Drexler, * E., Keilson, M., Wolintz, R., Drasby, E., Muscat, * P., Belden, J., Sullivan, R., Cohen, J., Stone, * L., Marrie, R. A., Fox, R., Hughes, B., Babikian, * P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, * W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, * G., Martin, J., Kaufman, D., Stuart, W., English, * J. B., Stuart, D. S., Gilbert, R. W., Kaufman, MS M., Putman, . *. S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, * E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, * H., Rizo, M., Kitaj, M., Blevins, Neurolo J., Smith, * T., Mcgee, F., Honeycutt, W., Brown, * M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, * J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, * S., Dorn, D., Groeschel, A., Kishner, B. Steingo* R., Cohen, B., Melen, * O., Simuni, T., Zee, P., Yerby, S. Cohan* M., Hendin, B., Levine, * T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, * R., Ferrell, W., Stefoski, D., Stevens, * S., Katsamakis, G., Topel, J., Ko, M., Fortin, D. Gelber* C., Green, B., Logan, * W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, * A., Sim, G., Mihai, C., Vertino, * M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, * A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, * A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, * J., Nicholas, A., Slaughter, R., Archer, R., Harik, * S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, * G., Olek, M., Demetriou, M., Shin, R., Cala bresi, * P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, * S., Sherbert, R., Herndon, R., Uschmann, * H., Chandler, A., Markowitz, C., Jacobs, * D., Balcer, L., Mitchell, G., Chakra vorty, * S., Heyman, R., Stauber, Z., Goodman, A., Segal, * B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, * M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, * M., Hawker, K., Ulrich, R., Panitch, H., Hamill, * R., Tandon, R., Dulaney, E., Simnad, V., Miller, * J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, * M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, * R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, * B., Hart, D., Moses, H., Sriram, * S., Fang, J., O’Duffy, A., Kita, M., Taylor, * L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, * S., Lefkowitz, D., Kumar, S., and Sinclair, M.

Published
2007

28. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

Author

Richard, A. Rudick, William, H. Stuart, Peter, A. Calabresi, Christian, Confavreux, Steven, L. Galetta, Ernst Wilhelm, Radue, Fred, D. Lublin, Bianca, Weinstock Guttman, Daniel, R. Wynn, Frances, Lynn, Msc, M. S. c., Michael, A. Panzara, Alfred, W. Sandrock, For, the SENTINEL Investigators including: F. Fazekas, Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher, A., Rothenfusser Körber, E., Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky D. Karusiss, O. Abramsky D. Karusiss, Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fern ez Fern ez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, L., Achtnichts, L., Wilmes, S., Karabudak, R., Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni ET Lim, G. Giovannoni E. T. Lim, Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss V. Gupta, M. Reiss V. Gupta, Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel A. Babu, A. Perel A. Babu, Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor S. Humphries, P. Fodor S. Humphries, Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., S. M, El, Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Kaiser, J. Javerbaum, Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo R. Kishner, B. Steingo R. Kishner, Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan M. Yerby, S. Cohan M. Yerby, Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., KoD Gelber C. Fortin, M. K. o. D. Gelber C. Fortin, Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, J., Nicholas, A., Slaughter, R., Archer, R., Harik, S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Ch ler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., R. T, On, Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Ari, D. B, Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair EW Radue, M. S. i. n. c. l. a. i. r. E. W. Radue, de Vera, A., Bacelar, O., Kuster, P., and Kappos, L. .

Subjects
Adult, Male, Infusions, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Combination therapy, Integrin alpha4, Peripheral edema, Progressive Multifocal, Relapsing-Remitting, Gastroenterology, Antibodies, Natalizumab, Drug Therapy, Leukoencephalopathy, Internal medicine, Monoclonal, Secondary Prevention, medicine, Humans, Humanized, Proportional Hazards Models, Expanded Disability Status Scale, business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Brain, Cell Adhesion Molecules, Disease Progression, Drug Therapy, Combination, Female, Infusions, Intravenous, Interferon-beta, JC Virus, Leukoencephalopathy, Progressive Multifocal, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Medicine (all), Progressive multifocal leukoencephalopathy, Multiple sclerosis, Hazard ratio, Interferon beta-1a, General Medicine, medicine.disease, Surgery, Combination, medicine.symptom, Intravenous, business, medicine.drug
Abstract

Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P

Published
2006

29. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis

Author

Patti, Francesco, Amato, Mp, Bastianello, S, Caniatti, L, Di Monte, E, Ferrazza, P, Goretti, B, Gallo, P, Morra, Vb, Lo Fermo, S, Picconi, O, Tola, Mr, Trojano, M, Batocchi, Anna Paola, Cogimus Study, Group, Patti, Francesco, Amato, Mp, Bastianello, S, Caniatti, L, Di Monte, E, Ferrazza, P, Goretti, B, Gallo, P, Morra, Vb, Lo Fermo, S, Picconi, O, Tola, Mr, Trojano, M, Batocchi, Anna Paola, and Cogimus Study, Group

Abstract

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score

Published
2010

30. Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study

Author

Patti, Francesca, Amato, Mp, Trojano, M, Bastianello, S, Tola, Mr, Goretti, B, Caniatti, L, Di Monte, E, Ferrazza, P, Brescia Morra, V, Lo Fermo, S, Picconi, O, Luccichenti, G, Batocchi, Anna Paola, Patti, Francesca, Amato, Mp, Trojano, M, Bastianello, S, Tola, Mr, Goretti, B, Caniatti, L, Di Monte, E, Ferrazza, P, Brescia Morra, V, Lo Fermo, S, Picconi, O, Luccichenti, G, and Batocchi, Anna Paola

Abstract

Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing-remitting (RR) MS is unclear.

Published
2009

31. FP21-TU-03 Serum N-acetyl aspartate (NAA) levels differ in multiple sclerosis (MS) and neuromyelitis optica (NMO)

Author

Tortorella, C., primary, Ruggieri, M., additional, Di Monte, E., additional, Pica, C., additional, Ceci, E., additional, Amato, M.P., additional, Ghezzi, A., additional, Lugaresi, A., additional, Patti, F., additional, Sola, P., additional, Zimatore, G.B., additional, Iaffaldano, P., additional, Direnzo, V., additional, Livrea, P., additional, and Trojano, M., additional

Published
2009
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32. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a oncognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis.

Author

Patti, F., Amato, M. P., Bastianello, S., Caniatti, L., Di Monte, E., Ferrazza, P., Goretti, B., Gallo, P., Morra, V. Brescia, Lo Fermo, S., Picconi, O., Tola, M. R., and Trojano, M.

Subjects
IMMUNOLOGICAL adjuvants, MAGNETIC resonance imaging, INTERFERONS, PHYSICIANS, MULTIVARIATE analysis, MULTIPLE sclerosis, PATIENTS
Abstract

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNβ-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score ≤4.0) were assigned IFNβ therapy at the physician's discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNβ-1a (44 mcg: n=236; 22 mcg: n=223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480-0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNβ-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNβ-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P=0.03), although a trend was also seen at the baseline (P=0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNβ-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26-0.99) compared with the lower dose of IFNβ-1a. These findings suggest that sc IFNβ-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNβ-1a treatment. [ABSTRACT FROM AUTHOR]

Published
2010
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33. New natural history of interferon-ß-treated relapsing multiple sclerosis.

Author

Trojano M, Pellegrini F, Fuiani A, Paolicelli D, Zipoli V, Zimatore GB, Di Monte E, Portaccio E, Lepore V, Livrea P, and Amato MP

Abstract

OBJECTIVE: To investigate the impact of interferon-beta (IFNbeta) on disease progression in relapsing-remitting multiple sclerosis patients. METHODS: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNbeta-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. RESULTS: The IFNbeta-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24-0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38-0.95 for time from first visit; HR, 0.54, 95% CI, 0.34-0.86 for time from date of birth; p

Published
2007
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34. Benefit of a multimodal approach combining chemotherapy and surgery in oligometastatic gastric cancer: experience from a tertiary referral center.

Author

Maratta MG, Vitale A, Basso M, Vivolo R, Di Monte E, Biondi A, Di Giorgio A, Rosa F, Tondolo V, Agnes A, Tortora G, Strippoli A, and Pozzo C

Abstract

Introduction: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC)., Methods: This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan-Meier method. Prognostic factors were assessed with the Cox model., Results: Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8-29.4) and median RFS was 10.6 mo. (95% CI 6.3-14.8). Pathologic response according to the Mandard criteria (TRG 1-3, not reached versus 20.5 mo. for TRG 4-5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series., Discussion: A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maratta, Vitale, Basso, Vivolo, Di Monte, Biondi, Di Giorgio, Rosa, Tondolo, Agnes, Tortora, Strippoli and Pozzo.)

Published
2024
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35. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry.

Author

Iaffaldano P, Lucisano G, Guerra T, Patti F, Cocco E, De Luca G, Brescia Morra V, Pozzilli C, Zaffaroni M, Ferraro D, Gasperini C, Salemi G, Bergamaschi R, Lus G, Inglese M, Romano S, Bellantonio P, Di Monte E, Maniscalco GT, Conte A, Lugaresi A, Vianello M, Torri Clerici VLA, Di Sapio A, Pesci I, Granella F, Totaro R, Marfia GA, Danni MC, Cavalla P, Valentino P, Aguglia U, Montepietra S, Ferraro E, Protti A, Spitaleri D, Avolio C, De Riz M, Maimone D, Cavaletti G, Gazzola P, Tedeschi G, Sessa M, Rovaris M, Di Palma F, Gatto M, Cargnelutti D, De Robertis F, Logullo FO, Rini A, Meucci G, Ardito B, Banfi P, Nasuelli D, Paolicelli D, Rocca MA, Portaccio E, Chisari CG, Fenu G, Onofrj M, Carotenuto A, Ruggieri S, Tortorella C, Ragonese P, Nica M, Amato MP, Filippi M, and Trojano M

Subjects
Humans, Immunologic Factors therapeutic use, Cross-Sectional Studies, Recurrence, Italy epidemiology, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis, Relapsing-Remitting chemically induced, Multiple Sclerosis, Chronic Progressive drug therapy
Abstract

Background: Active relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as "relapsing MS" (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD)., Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT's class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]., Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02-0.37), Natalizumab (0.48, 0.30-0.76), Ocrelizumab (0.1, 0.02-0.45) and Rituximab (0.23, 0.06-0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31-0.59), especially anti-CD20 drugs (0.14, 0.05-0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs., Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Published
2024
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36. Adjuvant denosumab in early breast cancer: a systematic review and meta-analysis of randomized controlled clinical trials.

Author

Mastrantoni L, Garufi G, Di Monte E, Maliziola N, Pasqualoni M, Pontolillo L, Pannunzio S, Cannizzaro MC, Di Bello A, Fabi A, Palazzo A, Tortora G, Bria E, and Orlandi A

Abstract

Background: In early breast cancer (BC) the impact of denosumab on survival outcomes is still unclear. We undertook a systematic review and meta-analysis to assess efficacy and safety of adjuvant denosumab in addition to standard anticancer therapy., Methods: PubMed, CENTRAL, Scopus, Embase, and oncological meetings websites were screened to identify potentially eligible randomized controlled trials (RCTs). Survival outcomes were disease-free survival (DFS), bone-metastasis-free survival (BMFS), and overall survival (OS). Fracture incidence and time to first fracture were bone-health outcomes. Osteonecrosis of the jaw (ONJ), atypical femur fractures (AFF), and other adverse events were also evaluated. Pooled hazard ratios (HRs) and risk ratios (RR) with respective 95% confidence interval (95% CI) were computed using a random-effects model. Exploratory subgroup analyses were performed., Results: Two phase III RCTs were included, the Austrian Breast & Colorectal Cancer Study Group-18 (ABCSG-18) and the D-CARE trials, for a total of 7929 patients. In the ABCSG-18 trial, denosumab was administered every 6 months during endocrine therapy (for a median of seven cycles) while the D-CARE trial used an intensive schedule for a total treatment duration of 5 years. Adjuvant denosumab showed no difference in DFS (HR: 0.932; 95% CI: 0.748-1.162), BMFS (HR: 0.9896; 95% CI: 0.751-1.070), and OS (HR: 0.917; 95% CI: 0.718-1.171) compared to placebo in the overall population. In hormone receptor positive/human epidermal growth factor receptor 2 (HER2) negative BC patients, a DFS (HR: 0.883; 95% CI: 0.782-0.996) and BMFS (HR: 0.832; 95% CI: 0.714-0.970) benefit was observed and BMFS was prolonged in all hormone receptor positive patients (HR: 0.850; 95% CI: 0.735-0.983). Fracture incidence (RR: 0.787; 95% CI: 0.696-0.890) and time to first fracture (HR: 0.760; 95% CI: 0.665-0.869) were also improved. No increase in overall toxicity was seen with denosumab and no differences were observed for ONJ and AFF between the 60-mg every 6-month schedule and placebo., Conclusion: Denosumab addition to anticancer treatment does not improve DFS, BMFS, or OS in the overall population, although a DFS improvement was observed in hormone receptor positive/HER2 negative BC patients and a BMFS improvement in all hormone receptor positive patients. Bone-health outcomes were improved with no added toxicity with the 60-mg schedule., Registration: PROSPERO identifier: CRD42022332787., Competing Interests: LM, GG, EDM, NM, MP, LP, SP, MCC, and ADB declare no conflict of interest. AP has declared consulting fees/advisory role for Amgen, MSD, Novartis, travel and accommodation by Pfizer. AF has declared consulting fees/advisory role for AstraZeneca, Daiichi Sankyo, Eisai, Eli-Lilly. Epionpharma, exact science, MSD, Novartis, Pierre Fabre, Roche, Seagen. GT is supported by funds of Ministero della Salute (Ricerca Corrente 2022). EB is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG20583. EB is supported by institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1). EB is supported by funds of Ministero della Salute (Ricerca Corrente 2022). EB received speakers’ and travels’ fee from MSD, AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, and Roche. EB received institutional research grants from AstraZeneca, Roche. AO has declared consulting fees/advisory role for Novartis, Roche, Eli-Lilly, Amgen, Daiichi Sankyo and travel and accommodation by Daiichi Sankyo, Novartis, Roche, and Pfizer., (© The Author(s), 2023.)

Published
2023
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37. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

Author

Riccio P, Rossano R, Larocca M, Trotta V, Mennella I, Vitaglione P, Ettorre M, Graverini A, De Santis A, Di Monte E, and Coniglio MG

Subjects
Adult, Anthropometry, Biomarkers analysis, Fatty Acids blood, Female, Gelatinases blood, Humans, Male, Middle Aged, Multiple Sclerosis, Chronic Progressive pathology, Neurologic Examination, Pilot Projects, Recurrence, Serum chemistry, Surveys and Questionnaires, Treatment Outcome, Vitamin D blood, Young Adult, Anti-Inflammatory Agents therapeutic use, Diet methods, Multiple Sclerosis, Chronic Progressive therapy
Abstract

The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status., (© 2016 by the Society for Experimental Biology and Medicine.)

Published
2016
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38. Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis.

Author

Patti F, Amato MP, Bastianello S, Caniatti L, Di Monte E, Ferrazza P, Goretti B, Gallo P, Morra VB, Lo Fermo S, Picconi O, Tola MR, and Trojano M

Subjects
Adolescent, Adult, Cognition Disorders etiology, Cohort Studies, Disability Evaluation, Disease Progression, Dose-Response Relationship, Drug, Endpoint Determination, Female, Humans, Injections, Subcutaneous, Interferon beta-1a, Interferon-beta administration & dosage, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting complications, Neuropsychological Tests, Prospective Studies, Survival Analysis, Young Adult, Cognition Disorders drug therapy, Cognition Disorders psychology, Immunologic Factors therapeutic use, Interferon-beta therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting psychology
Abstract

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score

Published
2010
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39. Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study.

Author

Patti F, Amato MP, Trojano M, Bastianello S, Tola MR, Goretti B, Caniatti L, Di Monte E, Ferrazza P, Brescia Morra V, Lo Fermo S, Picconi O, and Luccichenti G

Subjects
Adolescent, Adult, Age Factors, Cognition, Cognition Disorders epidemiology, Cognition Disorders etiology, Cross-Sectional Studies, Female, Humans, Immunologic Factors therapeutic use, Intelligence, Interferon-beta therapeutic use, Italy epidemiology, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting diagnosis, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Odds Ratio, Predictive Value of Tests, Prevalence, Prospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Treatment Outcome, Young Adult, Cognition Disorders diagnosis, Disability Evaluation, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting psychology, Neurologic Examination, Neuropsychological Tests
Abstract

Background: Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing-remitting (RR) MS is unclear., Objectives: To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS., Methods: Patients aged 18-50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score or=3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao's battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests., Conclusions: Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

Published
2009
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40. Subcutaneous Interferon Beta-1a Has a Positive Effect on Cognitive Performance in Mildly Disabled Patients with Relapsing-Remitting Multiple Sclerosis: 2-Year Results from the COGIMUS Study.

Author

Patti F, Amato MP, Bastianello S, Caniatti L, Di Monte E, Lijoi F, Goretti B, Messina S, Picconi O, Tola MR, and Trojano M

Abstract

The effect of interferon (IFN) beta-1a (44 and 22 μg subcutaneously [sc] three times weekly [tiw]) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (McDonald criteria; Expanded Disability Status Scale =4.0) was assessed by validated neuropsychological testing at baseline and at regular intervals for up to 2 years in this ongoing open-label, 3-year study. Year-2 data were available for 356 patients (22 μg, n = 175; 44μg, n = 181). The proportion of patients with impaired cognitive function was stable during the study: 21.4% at baseline and 21.6% at 2 years. At 2 years, the proportion of patients with =3 impaired cognitive tests was significantly lower in the 44 μg treatment group (17.0%) compared with the 22 μg group (26.5%; p = 0.034), although there was already a trend towards a higher proportion of patients with cognitive impairment in the 22 μg group at baseline. Factors associated with impairment in = three cognitive tests after 2 years were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00-1.09), verbal intelligence quotient (OR: 0.95; 95% CI: 0.92-0.98), and having = three impaired cognitive tests at baseline (OR: 11.60; 95% CI: 5.94-22.64). These interim results show that IFN beta-1a sc tiw may have beneficial effects on cognitive function as early as 2 years after treatment initiation, but the final 3-year data of the study are required to confirm these results.

Published
2009
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41. New natural history of interferon-beta-treated relapsing multiple sclerosis.

Author

Trojano M, Pellegrini F, Fuiani A, Paolicelli D, Zipoli V, Zimatore GB, Di Monte E, Portaccio E, Lepore V, Livrea P, and Amato MP

Subjects
Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Confidence Intervals, Disability Evaluation, Disease Progression, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting mortality, Proportional Hazards Models, Survival Analysis, Treatment Outcome, Immunologic Factors therapeutic use, Interferon-beta therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Objective: To investigate the impact of interferon-beta (IFNbeta) on disease progression in relapsing-remitting multiple sclerosis patients., Methods: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNbeta-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables., Results: The IFNbeta-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24-0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38-0.95 for time from first visit; HR, 0.54, 95% CI, 0.34-0.86 for time from date of birth; p < or = 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings., Interpretation: IFN-beta slows progression in relapsing-remitting multiple sclerosis patients.

Published
2007
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42. The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

Author

Trojano M, Russo P, Fuiani A, Paolicelli D, Di Monte E, Granieri E, Rosati G, Savettieri G, Comi G, and Livrea P

Subjects
Adjuvants, Immunologic therapeutic use, Adult, Analysis of Variance, Cohort Studies, Demography, Disability Evaluation, Disease Progression, Female, Humans, Italy epidemiology, Male, Middle Aged, Proportional Hazards Models, Regression Analysis, Risk, Time Factors, Treatment Outcome, Databases as Topic statistics & numerical data, Immunologic Factors therapeutic use, Interferon-beta therapeutic use, Multiple Sclerosis drug therapy, Multiple Sclerosis epidemiology
Abstract

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Published
2006
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43. Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis.

Author

Tortorella C, Bellacosa A, Paolicelli D, Fuiani A, Di Monte E, Simone IL, Giaquinto P, Livrea P, and Trojano M

Subjects
Adult, Age Factors, Brain physiopathology, Encephalitis physiopathology, Female, Gadolinium, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Multiple Sclerosis pathology, Multiple Sclerosis physiopathology, Predictive Value of Tests, Risk Factors, Aging pathology, Brain pathology, Encephalitis pathology, Multiple Sclerosis diagnosis
Abstract

There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.

Published
2005
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