PracticeUpdate Neurology February 2019

EDITOR’S PICKS 7

Abortion Induces Reactivation of Inflammation in Relapsing–RemittingMS Journal of Neurology, Neurosurgery, and Psychiatry Take-home message • Several studies have addressed the interaction between pregnancy and the course of multiple sclerosis (MS), but similar information is lacking with respect to abor- tion. This is a retrospective, multicenter, observational study assessing the course of relapsing–remitting MS in women undergoing spontaneous or elective abortions. The mean annualized relapse rate increased from 0.50 in the preconception year to 0.63 post abortion, and the mean number of gadolinium-enhancing lesions grew from 0.39 to 0.77. The main predictors of relapse were elective abortion (OR, 1.77), continuation of disease-modifying therapy at conception (OR, 0.71; meaning that treatment continuation reduced the risk), and higher preconception annualized relapse rate (OR, 1.32). • These data offer useful information for women with MS and the risks associated with abortion in this population. Codrin Lungu MD Abstract OBJECTIVE To investigate clinical and radiological outcomes of women with relapsing-remitting multiple sclerosis (RRMS) undergoing abortion. METHODS An independent, multicentre retrospective study was con- ducted collecting data from eight Italian MS centres. We compared the preconception and postabortion annualised relapse rate (ARR) and number of Gadolinium enhancing (Gd+) lesions, by analyses of covar- iance. Variables associated with postabortion clinical and MRI activity were investigated using Poisson regression models; each abortion was considered as a statistical unit. RESULTS From 1995 to 2017, we observed 188 abortions (17 elective) in 153 women with RRMS. Abortions occurred after a mean time of 9.5 (4.4) weeks from estimated conception date. In 86 events out of 188, conception happened during treatment with disease modifying drugs. The mean postabortion ARR (0.63±0.74) was significantly increased (p=0.037) compared with the preconception year (0.50±0.71) as well as the postabortion mean number of new Gd+ lesions (0.77±1.40 vs 0.39±1.04; p=0.004). Higher likelihood of relapses was predicted by higher preconception ARR, discontinuation of preconception treat- ment and elective abortion; the occurrence of new Gd+ lesions was associated with higher preconception number of active lesions, dis- continuation of preconception treatment, shorter length of pregnancy maintenance and elective abortion. CONCLUSIONS Abortion was associated with clinical and radiological inflammatory rebound remarkably in the first 12 months postevent. Deregulated proinflammatory processes arising at the early stages of pregnancy might play a role both in MS reactivation and abortion. Women with MS should be counselled about these risks of abortion and followed up accordingly. Abortion Induces Reactivation of Inflammation in Relapsing-Remitting Multiple Sclerosis. J Neurol Neurosurg Psychiatr 2018 Dec 01;89(12)1272-1278, D Landi,

Abstract IMPORTANCE Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS). OBJECTIVE To compare the effect of nonmyeloablative HSCT vs dis- ease-modifying therapy (DMT) on disease progression. DESIGN, SETTING, AND PARTICIPANTS Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disabil- ity Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South Amer- ican centers. Final follow-up occurred in January 2018 and database lock in February 2018. INTERVENTIONS Patients were randomized to receive HSCT along with cyclophosphamide (200 mg/kg) and antithymocyte globulin (6 mg/kg) (n=55) or DMT of higher efficacy or a different class than DMT taken dur- ing the previous year (n=55). MAIN OUTCOMES AND MEASURES The primary end point was disease pro- gression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evalua- tions 6 months apart, with differences in time to progression estimated as hazard ratios. RESULTS Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evalu- ated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95%CI, 0.02-0.24; P<.001). Dur- ing the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference, -1.7; 95% CI, -2.03 to -1.29; P<.001). There were no deaths and no patients who received HSCT developed non- hematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events). CONCLUSIONS AND RELEVANCE In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA 2019 Jan 15;321(2)165-174, RK Burt, R Balabanov, J Burman, et al. www.practiceupdate.com/c/78658

P Ragonese, L Prosperini, et al. www.practiceupdate.com/c/76841

VOL. 4 • NO. 1 • 2019