Author Of 2 Presentations
P0336 - Exposure to Natalizumab during pregnancy: A French national retrospective study (ID 890)
Pregnancy management in patients with relapsing-remitting multiple sclerosis (MS) treated by Natalizumab (NTZ) is challenging because of the risk of disease reactivation after treatment discontinuation.
To compare clinical disease activity (annual relapse rate) during and after pregnancy among three therapeutic approaches: continuation of NTZ all along the pregnancy and the postpartum, discontinuation of NTZ in the second trimester and discontinuation of NTZ before pregnancy.
Data were collected from the French MS registry OFSEP (Observatoire Français de la Sclérose en Plaques). We included patients with relapsing-remitting MS who started a pregnancy between 6/2013 and 9/2018 while taking NTZ, or within six months after its suspension. 3 groups were compared : continuation of NTZ throughout pregnancy and postpartum (Group 1), 3 to 6 months of exposure to NTZ during pregnancy (Group 2) and suspension prior to pregnancy (Group 3). Annual relapse rate (ARR) during 2 years (9 months before and 15 months after preganncy onset) was the primaty outcome and effect on EDSS and MRI were secondary end-points.
The main analysis was performed using a negative binomial regression with the follow-up duration as the offset term. Univariate and multivariate anlyses after adjustment for baseline variables (age, EDSS, ARR in the year before starting NTZ, first-line patient on NTZ vs. second-line patient).
117 patients from 27 centers* were included. Baseline mean age was 31,5 y, median EDSS was 2.0 and mean duration of disease was 7,89 y. The mean ARR were respectively 0.078 +/- 0.24 in Group 1, 0.308 +/- 0.43 in Group 2 and 0.456 +/- 0.63 in Group 3 during the observation period and was significantly higher in Groups 2 and 3 as compared with ARR in Group 1 (p=0,007). The risk of relapses was 4 times higher in Group 2 versus Group 1 (p=0,014) and 6 times higher in Group 3 versus Group 1 (p=0,001).
Multivariate analyses did not show any effect of the adjustment variables.
Evaluation of safety outcomes on the mother and the fetus is in progress.
* Investigators: AR, JCO, CD, PB (Bordeaux), SD, BA, AR, AM, CB, JP (Marseille), MD, S Pitton (Nancy), JD (Strasbourg), TM (Dijon), JC, D Biotti (Toulouse), OC, M Vaillant (Grenoble),E Berger (Besançon), D Laplaud (Nantes), G Defer (Caen), I Patry (Corbeil-Essonnes), P Vermersch (Lille), P Labauge (Montpellier), O Bourre (Rouen), B Stankoff (Paris-Saint-Antoine), A Créange (Créteil), P Cabre (Fort-de-France), E Thouvenot (Nîmes), T De Broucker (Saint-Denis), C Papeix (Paris-Salpêtrière), P Clavelou (Clermont-Ferrand), O Gout (Paris-F.Rothschild), A Montcuquet (Limoges), C Lebrun (Nice), O Heinzlef (Poissy) N Maubeuge (Poitiers).
Continuation of Natalizumab during all three trimesters of pregnancy is associated with a lower risk of relapses as compared with discontinuation before the pregnancy or even during the second trimester.
Safety data is being collected.
P0876 - High and low efficacy therapy in secondary progressive multiple sclerosis after accounting for therapeutic lag. (ID 760)
In secondary progressive multiple sclerosis (SPMS), reduction in the rates of disability accrual after starting disease modifying therapy (DMT) has largely been limited to patients with ongoing inflammatory activity. A delayed treatment effect, termed therapeutic lag, may obscure therapeutic benefits in SPMS.
To compare the effect of high and low efficacy DMT on disability outcomes in patients with recently active and inactive SPMS after accounting for therapeutic lag.
Using data from MSBase, a multinational MS registry, and OFSEP, the French MS registry, we identified patients with SPMS as per a previously validated objective definition. We identified patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferons, glatiramer acetate, teriflunomide) DMT after SPMS onset. Based on our previous work, an individualised estimate of duration of therapeutic lag was calculated for each patient. Only events that occurred after the estimated therapeutic lag period were included in the analysis. Propensity score matching was used to select groups with comparable baseline characteristics. Disability and relapse outcomes were compared in paired, pairwise-censored analyses adjusted for visit density.
Of 7359 patients with SPMS, 1000 patients fulfilled the criteria for study inclusion (510 active SPMS, 490 inactive SPMS). For the relapse outcomes, patients with active SPMS treated with high-efficacy DMTs experienced lower probabilities of relapses than low-efficacy DMTs (hazard ratio [HR] 0.7 [95%CI 0.5-0.9], p=0.006). Patients with inactive SPMS had similar probabilities of relapses in the high and low efficacy DMT groups (0.8 [0.6-1.2], p=0.39). No difference in the risk of 6-month sustained disability accumulation, or proportion of patients reaching EDSS>=7, was observed between groups when accounting for therapeutic lag.
The risk of disability accumulation in SPMS seems to be comparable in patients treated with high- and low- efficacy DMT. High efficacy DMT is superior to low efficacy therapy in reducing relapse activity in patients with active SPMS, but not those with inactive SPMS. Pre-treatment inflammatory activity, clinical or radiological, is a treatable target in SPMS which may benefit from higher-efficacy anti-inflammatory therapies.