The 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis – 18-20 September 2024
The following summarizes some of the highlights from Day 2 of ECTRIMS 2024.
Revised McDonald diagnostic criteria
Relapse risk with DMT de-escalation
Mononucleosis associated with 3-fold higher risk of MS
Anti-CD20 therapy effective after natalizumab
PIRA in CIS/early MS
Clinical tip of the day
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Revised McDonald diagnostic criteria
A number of important changes to the diagnosis of MS were introduced in the revised McDonald 2024 criteria (Montalban et al. ECTRIMS 2024;SS1). MS is no longer strictly a clinical diagnosis: paraclinical evidence of an abnormal brain/spinal MRI is required. In addition to brain/spinal cord lesions, dissemination in space (DIS) criteria now include the optic nerve as a fifth topography. Optic nerve pathology may be demonstrated with MRI, visual evoked potentials (VES) or optical coherence tomography (OCT). Two MRI signs – the central vein sign (CVS) and paramagnetic rim lesions (PRL) – have also been added to the criteria.
An MS diagnosis may be made in individuals with an abnormal MRI with typical MS lesions in ≥4 CNS topographies. If lesions are present in ≥2 topographies, either a positive CSF (OCB and/or kappa free light chain index as in the McDonald 2017 criteria), CVS lesions or DIT is needed. If lesions in only 1 anatomic area are present, MS may be diagnosed in patients with CSF+ and CVS+, CSF+ and PRL+, DIT and CVS+, or DIT and PRL+. For late-onset MS (age ≥50 years), obtaining evidence of additional features (SC lesion, CSF+, ≥6 CVS lesions) is recommended. For patients with evidence of disease progression ≥12 months, two spinal cord lesions are sufficient to show DIS. For individuals with radiologically isolated syndrome (RIS), an MS diagnosis can now be made if there is evidence of DIS (>2 topographies) + DIT, DIS + OCB+, or ≥6 CVS lesions.
Relapse risk with DMT de-escalation
An observational cohort analysis of the Austrian MS Treatment Registry examined the clinical impact of switching RRMS patients from a highly-active disease-modifying therapy to a modestly-effective DMT (Guger et al. ECTRIMS 2024;P320). The study sample was 389 patients who started treatment with natalizumab, ocrelizumab or ofatumumab and later switched to oral cladribine, dimethyl fumarate, an S1PR modulator or teriflunomide. The estimated annualized relapse rate (ARR) was 0.22 with highly-active treatment vs. 0.36 after de-escalation to a moderately-active DMT over a five-year period. EDSS scores significantly worsened during de-escalation from 2.8 to 3.1. The risk of EDSS progression after de-escalation was higher in patients who were older or had a higher EDSS score at the time of treatment switching.
Mononucleosis associated with 3-fold higher risk of MS
A matched-control study of two Danish health databases investigated the risk of developing MS in patients hospitalized for infectious mononucleosis (IM) in the period 1977 to 2022 (Kopp et al. ECTRIMS 2024;P075). Overall, 37,553 individuals were diagnosed with IM; mean age at IM diagnosis was 18.4 years. A total of 314 individuals subsequently developed MS; the incidence rate was 43.1 per 100,000 person-years vs. 15.0/100,000 PY for MS patients without a hospital diagnosis of IM. The risk of MS associated with IM hospitalization remained evident over the 40-year follow-up. MS risk was two-fold higher in patients diagnosed with IM during adolescence (ages 11-19 years) compared to those with an IM diagnosis in early childhood (hazard ratio 2.46) or adulthood (HR 2.06).
Anti-CD20 therapy effective after natalizumab
Two studies have examined the safety and efficacy of ofatumumab in patients discontinuing natalizumab. An Italian real-world study followed 38 patients who had switched from natalizumab to ofatumumab for >3 months (Camera et al. ECTRIMS 2024;P845). Mean age was 38 years; median EDSS score was 2.0. The median time from natalizumab discontinuation to start of ofatumumab was 37 days. There was no evidence of disease activity (relapses, new T2 lesions) at three months. At one year, 11% had experienced a relapse or new T2 lesions. The annualized relapse rate declined from 0.20 prior to the switch to 0.13 with ofatumumab. There were no cases of progressive multifocal leukoencephalopathy (PML) or other serious infections. Patients reported greater convenience with subcutaneous administration of ofatumumab compared to natalizumab infusions. A separate study looked at 32 patients (mean age 42 years) who had switched from natalizumab to ofatumumab (de Seze et al. ECTRIMS 2024;P1708). No patient experienced rebound after discontinuing natalizumab. The mean time to starting ofatumumab was 40 days.
PIRA in CIS/early MS
A multicentre German study examined the frequency of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in 1062 patients with CIS/early MS over a six-year follow-up period (Korsukewitz et al. ECTRIMS 2024;P072). Overall, 327 patients (31%) experienced sustained disability worsening. PIRA accounted for 32% of disability events compared to 18% for RAW. All other progression events were associated with minimal disability. Patients with PIRA were older than those with RAW at baseline (mean 39.5 vs. 34.7 years).
Clinical tip of the day
Heat-induced worsening of neurological symptoms, or Uhthoff’s phenomenon (UP), is generally assumed to be a short-term event and unrelated to the immunopathological changes seen in MS. A new study challenges this view (Bazzi et al. ECTRIMS 2024;P1318). A single-centre study found that 40 of 58 MS patients (69%) had heat-related symptoms, most commonly fatigue and muscle weakness. UP symptoms were often not transient: 42.5% reported that symptoms persisted for up to one day after heat exposure. Patients with UP were also found to have a higher number of supratentorial and spinal-cord lesions compared to patients without UP. One-third of patients reported improvement in UP symptoms after initiation of a disease-modifying therapy.