'A. Gemelli' IRCCS

Author Of 2 Presentations

Observational Studies Poster Presentation

P0883 - MRI activity and extended interval of Natalizumab dosing: a multicenter Italian study (ID 1269)

Abstract

Background

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML) without efficacy reduction.

Objectives

To evaluate the non-inferiority of the efficacy of an extended interval dosing (EID) regimen compared with the standard interval dosing (SID) of natalizumab regarding the multiple sclerosis (MS) MRI activity.

Methods

It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and eight patients were enrolled. Median dose interval (MDI) following 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks).

Results

Two hundred and sixteen patients were in the SID group (MDI = 4.4 weeks) and 144 in the EID group (MDI 6 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 2.98% (95% CI: 0.56-5.40) vs 3.32% (95% CI: 0.00-6.65%) [p=0.88] and 6.65% (95% CI: 3.02-10.29) vs 5.67% (95% CI: 1.76-9.58%) [p=0.73]. The EID regimen does not increase the occurrence of MRI activity after 6 and 12 months.

Conclusions

There is no evidence of a reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation confirms previous clinical results and together with the increasing evidence of a reduced risk of PML associated to an EID regimen, supports the need of a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, in order to better manage JCV-positive patients after 24 doses of natalizumab.

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Observational Studies Poster Presentation

P0913 - Risks associated with wash-out duration when switching from fingolimod to cell-depleting agents (ID 1317)

Abstract

Background

A wash-out duration lasting >1–2 months between the majority of sequential disease-modifying therapies (DMTs) is associated with an increased risk of disease reactivation in Multiple Sclerosis (MS) patients.

Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if lymphocyte recovery is still incomplete and that shorter wash-out periods do not affect the disease reactivation risk.

Objectives

To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent initiation in relation to the duration of wash-out between the drugs using data from the Italian MS Registry.

Methods

Patients who initiated alemtuzumab, rituximab, ocrelizumab or cladribine within six months of FTY discontinuation, and with a follow-up of at least six months, or until a relapse occurred, were included in the study. The risk of relapses was assessed in relation to different wash-out durations (<6, 6-11, 12-17 and >/=18 weeks) using a Poisson regression analysis (and reported as incidence rate ratio - IRR) and a Cox proportional hazards model including age, disease duration, relapses during FTY treatment, EDSS and reason for FTY discontinuation as covariates.

Results

Inclusion criteria were met by 329 patients (226F, 103M; mean age 41±10 years). Following a median wash-out period of 11 weeks [IQR: 6-16], 175 patients started alemtuzumab, 69 rituximab, 68 ocrelizumab and 17 cladribine. Ninety patients relapsed during the wash-out period and 72 during the subsequent cell-depleting therapy. During the cell-depleting treatment, IRR for a relapse was significantly greater in patients with a washout-period of 12-17 (IRR (95%CI): 2.4 (1,1-5,5); p=0.037) and >/=18 weeks (6.0 (2.8-12.7); p<0.001) compared to the reference period (<6 weeks).

The multivariable Cox analysis showed that the time to a relapse was significantly influenced by the occurrence of relapses during FTY treatment (HR (95%CI): 1.4 (1.2-1.7); p<0.001). Moreover, wash-out durations of 6-11, 12-17 and >/=18 weeks were associated with a higher risk of a relapse in comparison to wash-out durations shorter than 6 weeks (3.8 (1.1-13.2); p=0.037; 6.0 (1.7-21.9); p=0.006; 16.3 (4.8-56.3); p<0.001, respectively).

Conclusions

The risk of relapses during a cell-depleting therapy following a sequestering agent, namely FTY, increases progressively with the duration of wash-out, underlining the need of a short wash-out period also in this type of treatment sequence.

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