6. DISCUSSIONE
Questo studio retrospettivo mostra un importante effetto del farmaco teriflunomide nella riduzione dell’incidenza delle ricadute cliniche durante i primi 24 mesi di trattamento, sia nei pazienti naïve che in quelli che hanno effettuato precedenti DMT. Come conseguenza, l’ARR è stato di 0,09 e la percentuale di pazienti liberi da ricadute dopo 24 mesi è stata dell’83%, indipendentemente da precedenti trattamenti, età
98 d’inizio del trattamento, sesso ed EDSS basale. Nello studio TEMSO la teriflunomide 14 mg si era dimostrata in grado di ridurre l’ARR sia nei pazienti naïve, sia in quelli che avevano ricevuto precedenti DMT, con una leggera prevalenza di questi ultimi (senza però differenze statisticamente significative). In questo studio, invece, le riduzioni maggiori dell’ARR sono state registrate nelle sottopopolazioni naïve, con età < 50 anni e con EDSS basale < 3, anche se solo quest’ultimo gruppo ha raggiunto la significatività statistica. Durante i primi 24 mesi di terapia, nessun paziente ha registrato una progressione della disabilità. Sempre nel TEMSO la percentuale di pazienti che aveva raggiunto il NEDA dopo 2 anni di trattamento è stata del 21,2% e significativamente ridotta rispetto al placebo (p=0,0007), mentre in questa indagine la percentuale è risultata essere del 54,2% e la sua riduzione rispetto ai 24 mesi precedenti ha raggiunto la significatività statistica (p=0,012).
Riguardo al profilo di sicurezza e di tollerabilità, tutte le reazioni avverse sono risultate coerenti con quelle osservate durante lo sviluppo clinico del farmaco e rilevate dallo studio TEMSO. Nessun paziente ha sviluppato reazioni avverse non prevenibili e non derivabili dal meccanismo d’azione del farmaco. Inoltre, non si è verificato alcun caso di morte o altre reazioni severe. La percentuale di sospensione della teriflunomide a 24 mesi (30,2%) è risultata significativamente maggiore (p<0,001) rispetto allo studio di D’Amico et al174 (8,2%). La causa più frequente di sospensione della terapia
è stato lo scarso controllo della malattia, mentre la sospensione del trattamento per tutte le cause è risultata significativamente maggiore nei pazienti che avevano ricevuto precedenti DMT (p=0,047).
99 Per quanto concerne i limiti dello studio, quello più evidente è risultato sicuramente la scarsa numerosità del campione. La maggior parte dei risultati non ha raggiunto la significatività statistica, soprattutto nelle analisi condotte sul sottogruppo e in seguito alla stratificazione dei pazienti. Nonostante questo limite importante, alcuni dati si sono comunque dimostrati statisticamente significativi. Nel selezionare il sottogruppo per lo studio dell’efficacia del farmaco si sono verificati alcuni bias rilevanti. In primo luogo, molti dei pazienti che hanno introdotto la teriflunomide, sia come primo DMT, sia dopo il fallimento di altri trattamenti, lo hanno fatto dopo un periodo di ricadute cliniche e radiologiche. Secondariamente, molti dei pazienti che hanno avuto gli stessi eventi successivamente all’inizio del farmaco sono stati esclusi dal sottogruppo in quanto, a causa della precoce sospensione, non hanno raggiunto i 12 mesi di trattamento (criterio B-a). Appare quindi ragionevole che questi bias abbiano contribuito a rendere più positivi i valori relativi all’efficacia del trattamento.
100
7. CONCLUSIONI
Negli ultimi 25 anni si è assistito a un sostanziale progresso del trattamento della SM. L’avanzamento nello sviluppo di nuovi agenti terapeutici è stato un risultato diretto dei trial clinici che hanno documentato la loro efficacia. La teriflunomide ha dimostrato efficacia e sicurezza in una serie di studi di fase III come trattamento della malattia. Il vantaggio della via di somministrazione orale e la buona tollerabilità l a rendono una valida alternativa nell’armamentario terapeutico a disposizione nei confronti della SM remittente-recidivante. Con le crescenti opzioni di trattamento, sia orale che parenterale, diventa necessario stabilire il ruolo destinato ad essere ricoperto da questo farmaco.
Questo studio, pur tenendo conto dei limiti sopracitati, contribuisce ad aumentare la raccolta di informazioni a disposizione riguardanti la teriflunomide. Data l’elevata percentuale di sospensioni del trattamento, anche rispetto ad altri studi, sembra necessario migliorare i criteri di selezione dei pazienti a cui prescrivere la terapia e delineare così il profilo ideale del paziente candidabile ad iniziare il trattamento, in modo da ridurre gli switch terapeutici. Dai nostri dati sembra emergere una maggiore efficacia del farmaco nei pazienti naïve rispetto a quelli che hanno già ricevuto altre terapie; questo potrebbe suggerire un utilizzo preferenziale del farmaco come primo trattamento, piuttosto che come alternativa in caso in cui altri siano risultati inefficaci. Nonostante il campione in esame sia troppo esiguo per poter formulare tali deduzioni, queste informazioni possono costituire un punto di partenza per studi su popolazioni più numerose, anche integrando questi dati con quelli provenienti da altri centri.
101
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