Early switch to fingolimod may decrease the risk of disease recurrence after natalizumab interruption

We read with interest the case report by Daelman et al., regarding a severe reactivation of multiple sclerosis (MS) in a woman who switched from natalizumab (NTZ) to fingolimod (FTY). 1 Here we report the follow-up of 19 subjects who withdrew NTZ at the MS Clinic, University of Genoa, Italy from January 2011 to January 2012 and subsequently began, in a non-randomized fashion, FTY (n=11) (7/11 started FTY in the framework of the open-label study with FTY, Protocol CFTY720DIT03), another immunomodulatory (IM) agent (either interferon-beta or glatiramer acetate (GA), n=4) or remained untreated (n=4). The FTY group included one subject initially treated with GA for 12 weeks who switched to FTY due to cutaneous side effects. NTZ was stopped after a mean of 30.42 months (standard deviation (SD) 12.94), due to drug-associated risk2 or patient’s decision. The treatment groups were homogenous as per demographic and disease characteristics (Table 1). Four out of 11 subjects in the FTY group and all the others received intravenous high dose methylprednisolone (MP) pulses as an arbitrary attempt to prevent disease exacerbation. Fewer subjects in the FTY group received MP pulses in order to accelerate the enrollment into the open-label study with FTY that required washout of steroids before inclusion. In detail, patients were scheduled to receive three to four courses of 1 gram MP intravenously once a day starting at 90, 135 and 180 days after stopping NTZ. The schedule was changed in the case of a relapse or due to intolerance to MP. Mean dose of MP administered (including the treatment of relapses) was 1.9 g (±2.7) for patients who switched to FTY, 7.4 g (±4.9) for patients who started another IM, and 10.0 g (±6.8) for those who remained untreated. Time to new treatment was 18.84±5.45 weeks for those who started FTY and 14.29±2.94 weeks for those who started another IM drug (p= not significant (ns)). The number of relapses occurring between 13 weeks (mean time required by serum NTZ concentration to decrease to nontherapeutic values3) and 34 weeks post NTZ interruptions were compared among groups. We observed an unbalanced distribution of relapses depending on the chosen treatment. In detail, one relapse occurred in 1/11 subjects who started FTY and in 5/8 subjects who remained untreated or started another IM drug (respectively 3/4 and 2/4) (Exact Chi-square test, p=0.03 FTY vs other IM agents vs untreated; p=0.04 FTY vs others) (Figure 1). Relapses required hospitalization in four cases (none in the FTY group). Of note, the only subject having a relapse in the FTY group was the one who had been treated with GA for 12 weeks after NTZ and started FTY later (31 weeks post NTZ stop). The administration of MP did not prevent the occurrence of a relapse. FTY treatment was well tolerated without serious adverse events. In summary, despite the limited number of cases and the observational nature of this report, we observed a better control of relapses in subjects with similar disease characteristics who switched from NTZ to FTY compared to those who remained untreated or started another IM drug. We may speculate on a possibly synergic effect of NTZ and 468498 MSJ19910.1177/1352458512468498Multiple Sclerosis JournalLaroni et al. 2012