Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis

• Published in: Brain (London, England : 1878) England : 1878), 2015-11, Vol.138 (Pt 11), p.3275-3286
• Main Authors: Iaffaldano, Pietro, Lucisano, Giuseppe, Pozzilli, Carlo, Brescia Morra, Vincenzo, Ghezzi, Angelo, Millefiorini, Enrico, Patti, Francesco, Lugaresi, Alessandra, Zimatore, Giovanni Bosco, Marrosu, Maria Giovanna, Amato, Maria Pia, Bertolotto, Antonio, Bergamaschi, Roberto, Granella, Franco, Coniglio, Gabriella, Tedeschi, Gioacchino, Sola, Patrizia, Lus, Giacomo, Ferrò, Maria Teresa, Iuliano, Gerardo, Corea, Francesco, Protti, Alessandra, Cavalla, Paola, Guareschi, Angelica, Rodegher, Mariaemma, Paolicelli, Damiano, Tortorella, Carla, Lepore, Vito, Prosperini, Luca, Saccà, Francesco, Baroncini, Damiano, Comi, Giancarlo, Trojano, Maria
• Format: Article
• Language: English
• Subjects: Adult; Cohort Studies; Drug Substitution; Drug Therapy, Combination; Female; Fingolimod Hydrochloride - therapeutic use; Glatiramer Acetate - therapeutic use; Humans; Immunologic Factors - therapeutic use; Immunosuppressive Agents - therapeutic use; Interferon-beta - therapeutic use; Italy; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab - therapeutic use; Poisson Distribution; Prospective Studies; Registries; Regression Analysis; Treatment Outcome
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awv260

The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a supe