L’artrite reumatoide è una malattia degenerativa a carattere sistemico che comporta un notevole impatto sull’autonomia e sull’abilità lavorativa
dell’individuo, oltre che una riduzione dell’aspettativa di vita. Per contrastare la diffusione di questa patologia è necessario implementare
opportune strategie di prevenzione primaria (mediante la diffusione di interventi di contrasto alla sedentarietà e di promozione di stili di vita attivi) e di diagnosi precoce sensibilizzando i pazienti a collaborare consapevolmente alla terapia che in una prima fase della malattia si avvale di un trattamento farmacologico standard, mentre i nuovi orizzonti terapeutici sono orientati all’utilizzo dei farmaci biologici che richiedono un monitoraggio clinico a lungo termine, imponendo l’attivazione di veri e propri registri, allo scopo di monitorare il profilo rischio/beneficio nel tempo.
Considerando le forti evidenze del coinvolgimento dell’IL-6 nella patogenesi dell’AR, lo sviluppo di agenti che mirano al blocco dell’IL-6 o del suo recettore, ha acquisito un’importanza significativa come nuova opzione terapeutica per il trattamento della malattia. Tocilizumab è stato il primo bloccante di IL-6 commercializzato, attualmente utilizzato per la gestione dei pazienti che danno risposta insufficiente sia con MTX che con inibitori di TNF (Smolen e coll., 2014). Sia le sperimentazioni cliniche che i dati della vita reale, dimostrano chiaramente l’efficacia di tocilizumab, in combinazione con MTX, nel produrre una significativa risposta clinica, nel miglioramento della funzione fisica e nella prevenzione della progressione radiografica. Inoltre, la monoterapia con tocilizumab ha mostrato un’efficacia clinica superiore rispetto alla monoterapia con MTX nello studio AMBITION (Jones e coll., 2009), rispetto ad adalimumab nello
105 studio ADACTA (Gabay e coll., 2016), ed un’efficacia clinica e radiografica simile rispetto alla combinazione con MTX nello studio ACT- RAY (Dougados e coll., 2014). Successive sperimentazioni cliniche hanno portato allo sviluppo di nuovi agenti biologici che mirano a legarsi con l’ IL-6 e/o il suo recettore con maggiore affinità, quali sirukumab, olokizumab, calazakizumab e sarilumab (Kim e coll., 2015). Quest’ultimo è un anticorpo monoclonale umano 20 volte superiore a tocilizumab: i dati preclinici su sarilumab hanno rivelato un’inibizione dose-dipendente del segnale dell’IL-6 con una concentrazione inferiore a quella del tocilizumab, e senza evidenze di citotossicità cellula mediata (Rafique e coll., 2013). I profili di efficacia e sicurezza di sarilumab sono stati testati in studi clinici per il trattamento di pazienti con AR attiva, che non hanno risposto o sono intolleranti al MTX o ad inibitori del TNF (Van Ray e coll., 2015; Genovese e coll., 2014). Ad oggi è possibile affermare che il Sarilumab rappresenta il capostipite degli inibitori dell’IL-6 per il trattamento dell’artrite reumatoide; l’analisi dei diversi studi, ha permesso di identificare tutta la vasta gamma di possibili eventi avversi che possono manifestarsi in seguito all’assunzione di tale farmaco e ne hanno fornito una revisione completa del profilo di efficacia e tollerabilità. Concludo sostenendo che occorrono ulteriori studi per rilevare eventi avversi rari che potrebbero verificarsi dopo un periodo prolungato di esposizione al Sarilumab, al fine di migliorarne e aggiornarne il profilo di sicurezza e far
sì che questo farmaco possa costituire uno dei farmaci di prima scelta per il trattamento dell’AR.
106
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