The study involved 613 patients from the Italian iMedWeb registry who had relapsing multiple sclerosis (MS) and stopped natalizumab. The researchers analysed the risk of relapse during the wash-out period and after switching to a new therapy. They found that patients with a higher number of relapses before natalizumab treatment and those discontinuing natalizumab due to lack of efficacy, patient's choice, or adverse events had an increased risk of relapses during the wash-out period. Factors such as a wash-out duration longer than three months, the number of relapses experienced before and during natalizumab treatment, and the presence of comorbidities influenced the relapse risk after starting switch therapies.

Switching to fingolimod was associated with a 64% reduction in the risk of relapse compared to switching to interferon beta/glatiramer acetate. The researchers performed propensity score matching, creating a sample of patients who switched to either fingolimod or interferon beta/glatiramer acetate, and found a significantly lower incidence of relapses in patients treated with fingolimod during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch
was also significantly lower in patients receiving fingolimod. These results were consistent across subgroups with different
wash-out durations. The study indicated that fingolimod was superior to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in real-life settings. It also suggested that more aggressive treatments should be considered early in the disease course for patients with a highly active presentation.

Furthermore, a wash-out duration longer than 1-3 months after natalizumab cessation was deemed unacceptable in clinical practice. In terms of disability progression, there was no significant difference between the two groups over the 12-month follow-up period. The rate of confirmed disability progression events was 11% in patients receiving fingolimod and 22% in those receiving interferon beta/glatiramer acetate.

These findings align with previous studies that highlighted the potential of fingolimod in reducing disease reactivation after natalizumab withdrawal. However, this study is the first comparative effectiveness study of fingolimod versus interferon beta/glatiramer acetate in a real-world setting, confirming the superiority of fingolimod.

In conclusion, managing treatment sequencing in relapsing MS patients who discontinue natalizumab is a challenge. The study demonstrated that switching to fingolimod resulted in a lower risk of relapse compared to switching to interferon beta/glatiramer acetate. These results suggest the importance of considering more aggressive treatments early in the disease course and avoiding wash-out durations longer than 1-3 months after natalizumab cessation. However, both fingolimod and interferon beta/glatiramer acetate showed similar rates of disability progression.

Reference:

Iaffaldano P, Lucisano G, Pozzilli C, et al. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. Brain 2015;138:3275-86.