Contributions
Abstract: P326
Type: Poster
Abstract Category: Clinical aspects of MS - 4 Natural course
Background: While the influence of pregnancy in multiple sclerosis (MS) has been well established, there is no data on the effect of miscarriage on the short-term disease course.
Objective: To investigate the post-miscarriage clinical and radiological outcomes of women with relapsing remitting MS (RRMS).
Methods: An independent, multi-center retrospective study was performed by collecting data of women with RRMS who regularly attended four Italian MS centers. We compared pre- and post-miscarriage annualized relapse rate (ARR) and the number of Gd+ lesions as detected on the pre-conception and the post-miscarriage MRI scan, by analyses of covariance. Variables associated with post-miscarriage clinical and MRI activity were investigated using Poisson regression models. Each miscarriage was considered as a statistical unit.
Results: From 1983 to 2016 we observed 88 miscarriages (2 induced) in 69 women. The mean (SD) age at miscarriage was 34.3 (5.6) years. Miscarriage occurred after a mean time of 9.6 (3.4) weeks from the estimated conception date. Conception happened during treatment with disease modifying drugs (DMT) in 62 events out of 88 (45 inteferon beta, 9 natalizumab, 6 glatiramer acetate, 2 FTY720). The post-miscarriage mean ARR (0.38+/-0.53) was unchanged compared with pre-miscarriage ARR (0.47 +/- 0.68, p=0.29). The post-miscarriage mean number of Gd+ lesions (0.76 +/- 1.54) was significantly increased compared with the pre-conception MRI scan (0.36 +/-0.81, p=0.02). This finding remains unaltered after correcting for age at miscarriage, pre-conception and post-miscarriage DMT, time elapsed from the miscarriage to MRI scan. Occurrence of post-miscarriage Gd+ lesions was inversely correlated with the length of pregnancy maintenance (OR=0.78, p=0.01) and directly correlated with the pre-conception number of Gd+ lesions (OR=1.96, p=0.008).
Conclusions: Miscarriage induces disease reactivation possibly due to the recovery of the immunocompetence, as postulated in successful pregnancy in MS. We hypothesize that the inverse correlation between pregnancy length and the occurrence of new Gd+ lesions, might be explained by pro-inflammatory processes, essential for implantation and pregnancy maintenance, and by low production of estriol not yet reaching protective levels, both occurring at very early pregnancy.
References: Vukusic S et al.Brain 2004 Jun;127:1353-60, Mor G et al. Ann N Y Acad Sci 2011 Mar;1221:80-7, Sicotte NL et al. Ann Neurol 2002 Oct;52(4):421-8
Disclosure:
Doriana Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Antonio Cortese received travel funding and honoraria for speaking from Biogen, Sanofi-Genzyme and Teva.
Claudia Martinelli declares that she has no competing interests.
Roberta Fantozzi received honoraria for speaking or consultation fees from Almirall, Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Teva, and was an Advisory Board member of Biogen, Merck-Serono, Novartis, Teva.
Simona Pontecorvo received honoraria from Almirall, Biogen, Sanofi-Genzyme, Merck Serono, Novartis, Teva.
Luca Prosperini received consulting and/or lecture fees and travel grant from Biogen, Merck Serono, Novartis, Roche Sanofi-Genzyme and Teva.
Giorgia Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme.
Enrico Millefiorini received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva
Ada Francia received honoraria from Almirall, Biogen, Merck Serono, Novartis, Sanofi-Genzyme and Teva.
Carlo Pozzilli has received consulting and/or lecture fees and/or research funding and travel grant from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva.
Laura Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
Diego Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck-Serono, Novartis, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer, Biogen, Merck Serono, Novartis e Teva.
Girolama Alessandra Marfia is an Advisory Board member of Biogen, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.
Abstract: P326
Type: Poster
Abstract Category: Clinical aspects of MS - 4 Natural course
Background: While the influence of pregnancy in multiple sclerosis (MS) has been well established, there is no data on the effect of miscarriage on the short-term disease course.
Objective: To investigate the post-miscarriage clinical and radiological outcomes of women with relapsing remitting MS (RRMS).
Methods: An independent, multi-center retrospective study was performed by collecting data of women with RRMS who regularly attended four Italian MS centers. We compared pre- and post-miscarriage annualized relapse rate (ARR) and the number of Gd+ lesions as detected on the pre-conception and the post-miscarriage MRI scan, by analyses of covariance. Variables associated with post-miscarriage clinical and MRI activity were investigated using Poisson regression models. Each miscarriage was considered as a statistical unit.
Results: From 1983 to 2016 we observed 88 miscarriages (2 induced) in 69 women. The mean (SD) age at miscarriage was 34.3 (5.6) years. Miscarriage occurred after a mean time of 9.6 (3.4) weeks from the estimated conception date. Conception happened during treatment with disease modifying drugs (DMT) in 62 events out of 88 (45 inteferon beta, 9 natalizumab, 6 glatiramer acetate, 2 FTY720). The post-miscarriage mean ARR (0.38+/-0.53) was unchanged compared with pre-miscarriage ARR (0.47 +/- 0.68, p=0.29). The post-miscarriage mean number of Gd+ lesions (0.76 +/- 1.54) was significantly increased compared with the pre-conception MRI scan (0.36 +/-0.81, p=0.02). This finding remains unaltered after correcting for age at miscarriage, pre-conception and post-miscarriage DMT, time elapsed from the miscarriage to MRI scan. Occurrence of post-miscarriage Gd+ lesions was inversely correlated with the length of pregnancy maintenance (OR=0.78, p=0.01) and directly correlated with the pre-conception number of Gd+ lesions (OR=1.96, p=0.008).
Conclusions: Miscarriage induces disease reactivation possibly due to the recovery of the immunocompetence, as postulated in successful pregnancy in MS. We hypothesize that the inverse correlation between pregnancy length and the occurrence of new Gd+ lesions, might be explained by pro-inflammatory processes, essential for implantation and pregnancy maintenance, and by low production of estriol not yet reaching protective levels, both occurring at very early pregnancy.
References: Vukusic S et al.Brain 2004 Jun;127:1353-60, Mor G et al. Ann N Y Acad Sci 2011 Mar;1221:80-7, Sicotte NL et al. Ann Neurol 2002 Oct;52(4):421-8
Disclosure:
Doriana Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Antonio Cortese received travel funding and honoraria for speaking from Biogen, Sanofi-Genzyme and Teva.
Claudia Martinelli declares that she has no competing interests.
Roberta Fantozzi received honoraria for speaking or consultation fees from Almirall, Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Teva, and was an Advisory Board member of Biogen, Merck-Serono, Novartis, Teva.
Simona Pontecorvo received honoraria from Almirall, Biogen, Sanofi-Genzyme, Merck Serono, Novartis, Teva.
Luca Prosperini received consulting and/or lecture fees and travel grant from Biogen, Merck Serono, Novartis, Roche Sanofi-Genzyme and Teva.
Giorgia Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme.
Enrico Millefiorini received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva
Ada Francia received honoraria from Almirall, Biogen, Merck Serono, Novartis, Sanofi-Genzyme and Teva.
Carlo Pozzilli has received consulting and/or lecture fees and/or research funding and travel grant from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva.
Laura Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
Diego Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck-Serono, Novartis, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer, Biogen, Merck Serono, Novartis e Teva.
Girolama Alessandra Marfia is an Advisory Board member of Biogen, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.