Allan G Kermode

Introduction: Vascular comorbidities (VCM) are common in patients with multiple sclerosis (MS). VCM are associated with increased disease activity and disability progression, but long-term clinical follow-up data in larger cohorts is limited.

Objectives/Aims: To investigate whether VCM are associated with relapse rates or disability progression in relapsing-remitting MS (RRMS).

Methods: We analysed longitudinal data from MSBase, an international prospective registry of patients with MS. Adults with RRMS, no relapses over the preceding year and no commencement or switching of disease-modifying therapy (DMT) were identified from 2015–2017. Included participants were followed up for 5 years. Baseline VCM (hypertension, hyperlipidaemia, diabetes, ischaemic heart disease) were analysed as individual VCM and as cumulative count of VCM (0/1/2+). Poisson and Cox regression were used to investigate the association between VCM, relapse rates and disability progression over 5 years of follow-up, respectively, with models adjusted for age, sex, disease duration and baseline DMT. As a sensitivity analysis, we analysed a subgroup of 18 sites participating in the MSBase Safety substudy with more complete registry data.

Results: 42185 participants were followed-up over 5 years. The mean age was 44.4 years (SD 12.7), and 72.3% were female. Recorded VCM were hypertension (n=912), diabetes (n=451), hyperlipidaemia (n=325) and ischaemic heart disease (n=186). Median Expanded Disability Status Scale (EDSS) was 2.0 at baseline (IQR 1.0–4.0) and 2.5 at 5 years (IQR 1.5–5.5).

7454 participants (17.7%) had 1 or more relapses over 5 years. Hypertension was associated with increased relapse rate (IRR [95% CI] 1.75 [1.55–1.99]; p<0.001), as were hyperlipidaemia (IRR 1.93 [1.58–2.35]; p<0.001) and diabetes (IRR 1.89 [1.61–2.22]; p<0.001), but not ischaemic heart disease (IRR 1.28 [0.96–1.70]; p=0.09). The relapse rate was increased in those with 1 VCM (IRR 1.81 [1.64–2.00]; p<0.001) and 2 VCM+ (IRR 1.74 [1.36–2.23]; p<0.001), compared to those with no VCM. In the sensitivity analysis, hypertension (IRR 1.20 [1.01–1.42]; p=0.04), diabetes (IRR 1.74 [1.44–2.09]; p<0.001) and 1 VCM (IRR 1.37 [1.20–1.57]; p<0.001) were also associated with increased relapse rates. VCM were not associated with EDSS worsening.

Conclusion: Vascular risk factors are associated with increased disease activity over 5 years in RRMS.

Introduction: Family planning is an integral aspect in the care of women with multiple sclerosis (MS). As disease-modifying therapy (DMT) discontinuation may increase relapse activity, treatment benefits need to be carefully balanced against the risk to the unborn. Ocrelizumab may be a suitable option for women with MS who are planning to conceive, but real-world data on disease activity during pregnancy and postpartum versus other DMTs are scarce.

Objectives/Aims: To describe relapse activity in women with MS before, during and after pregnancy treated with ocrelizumab versus other DMTs.
Methods: Pregnancies in women with MS recorded in MSBase since 2011 up to 1st March 2023 treated with ocrelizumab (OCR), natalizumab (NAT), dimethyl fumarate (DMF) or low-efficacy DMT (interferon-beta, glatiramer acetate) before pregnancy were included. Annualised relapse rates (ARR) were calculated per three-month period for the one-year preconception, during and after pregnancy.

Results: A total of 1654 women with 1901 pregnancies were included (OCR, n=58; NAT, n=398; DMF, n=156; low-efficacy DMT, n=1289). For NAT, use was further subset into continuation into pregnancy third trimester with early (⩽1 month) postpartum re-initiation (NAT-E, n=77)), and cessation prior to four-weeks gestation with late postpartum re-initiation (NAT-L, n=79). One-year preconception ARR [95% CI] was 0.15 [0.06-0.30] for OCR; 0.11 [0.08-0.15] for NAT; 0.12 [0.07-0.19] for DMF; and 0.22 [0.19-0.25] for low-efficacy DMT. During pregnancy, ARR [95% CI] was 0 [0-0.09] for OCR; 0.04 [0-0.13] for NAT-E; 0.34 [0.20-0.52] for NAT-L; 0.12 [0.07-0.21] for DMF; and 0.12 [0.10-0.14] for low-efficacy DMT. Postpartum ARR [95% CI] was 0.11 [0.02-0.33] for OCR; 0.11 [0.03-0.28] for NAT-E; 0.77 [0.52-1.11] for NAT-L; 0.41 [0.28-0.59] for DMF; and 0.43 [0.38-0.49] for low-efficacy DMT. Three women treated with ocrelizumab preconception experienced a postpartum relapse, two of which occurred prior to ocrelizumab re-initiation; none of these women had relapses pre-conception or during pregnancy.

Conclusion: This real-world analysis suggests that women with MS receiving ocrelizumab pre-conception are likely at low risk for within-pregnancy relapse and not at increased risk of postpartum relapses. However, treatment pauses after birth may increase relapse risk. Further data including predictors of postpartum relapses are warranted to ensure optimal care to women with MS and their infants.

Background: Little is known about the underlying genetic basis of neuromyelitis optica spectrum disorder (NMOSD). Objective: To identify the causative gene in a Chinese family with NMOSD. Methods: Whole-exome sequencing was performed in 4 members of this family(2 with NMOSD, and 2 family controls), supplemented by independent HLA-DP genotyping. Results: One mutation chr6:42902216,G>A within the CNPY3 gene, which co-segregated with the NMOSD phenotype in this pedigree was identified. CNPY3 gene encodes the protein which is associated with toll-like receptors function. It may involve in the NMOSD pathogenesis by changing the activity of TLRs. There was no HLA-DP allele co-segregated with the NMOSD phenotype found in this family. Conclusions: CNPY3 gene was implicated as a novel gene mutated in a Chinese family with NMOSD. Replication studies in other familial NMOSD cases and case-control studies are undergoing to verify the preliminary association.