Efficacy and Side Effects of Natalizumab Therapy in Patients with Multiple Sclerosis

Abstract

Natalizumab (Nat) is a humanized monoclonal antibody used for the treatment of relapsing multiple sclerosis (MS). Nat inhibits lymphocyte migration via the blood brain barrier (BBB) by blockage of an integrin adhesion molecule, very late antigen 4. During the phase III clinical trials, it was shown that Nat reduces disease activity and prevents disability progression. In addition, several smaller studies indicate a positive influence of Nat on cognition, depression, fatigue, and quality of life (Qol). Therapeutic efficacy has to be weighed against the risk of developing potentially fatal progressive multifocal leukoencephalopathy (PML), an opportunistic infection by JC-virus (JCV) with an incidence of 3.4/1000 (95% CI 3.08–3.74) in Nat treated MS patients. In this review article, we will review data on the presumed mechanism of Nat action, clinical and paraclinical efficacy parameters, and adverse drug reactions with a special focus on PML.

Fatigue in multiple sclerosis – Insights into evaluation and management

“…For example, interferon-beta can induce and/or aggravate fatigue [16]. Conversely, natalizumab (a monoclonal antibody) could lessen fatigue [86].…”

Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis

“…Subsequently, glatiramer acetate was introduced as a MS drug, which affects antigen presentation and cytokine balance (Caporro et al 2014). The humanized anti-VLA-4 monoclonal antibody, natalizumab, inhibits T-cell infiltration into the CNS (Hoepner et al 2014). Fingolimod was the first MS oral drug, which inhibited T-cell migration (Kim et al 2015).…”

Come modificare la terapia nel paziente experienced

“…Lo studio in questione ha documentato nel gruppo dei trattati con natalizumab una maggiore percentuale di pazienti liberi da ricadute (p <0,0001), progressione di disabilità (p = 0,0045) e attività di malattia in RM (p = 0,0003) rispetto a quelli trattati con farmaci di prima linea [37]. A conferma di questo studio, anche altri studi osservazionali, tra cui il TOP (Tysabri Observational Program) [38], hanno documentato l'efficacia di natalizumab in pazienti con risposta subottimale ai farmaci di prima linea [39,40]. Anche lo shift verso fingolimod è supportato dai dati derivati dai trials registrativi del farmaco e da loro sottoanalisi.…”