8th Joint Americas Committee and European Committee for Treatment and Research in MS (ACTRIMS-ECTRIMS) meeting, Virtual Congress, 11-13 September 2020.
The following summarizes some of the highlights from Day 1 of ACTRIMS-ECTRIMS 2020.
CONGRESS HIGHLIGHTS – FRIDAY EDITION
Ocrelizumab: The rate of 48-week confirmed disability progression (CDP) during the long-term extension of the ORATORIO trial was 30.5% at week 168, and 54.2% at week 360 (7 years) with continuous ocrelizumab (Wolinsky et al. ECTRIMS 2020; abstract P0237). The proportion of patients with 48-week confirmed EDSS >7 was 4.8% at week 168, and 12.3% at week 360. The proportion with 48-week confirmed worsening on the 9-Hole Peg Test was 15.8% and 31.1% at weeks 168 and 360, respectively. The risk of reaching EDSS 7 was 44% lower in patients on continuous ocrelizumab versus those in the placebo-ocrelizumab switch group.
Cladribine: Annualized relapse rates remained low over five years in the long-term extension of the CLARITY trial (Giovannoni et al. ECTRIMS 2020; abstract P0202). In the subgroup that received a cumulative dose of cladribine 3.5 mg/kg over the first two years, ARR ranged from 0.10 to 0.15 in years 2-5 (with no further dosing). There was no increase in relapses in the three years after the dosing regimen was completed.
Siponimod: Continuous treatment with siponimod appears to have a durable effect on relapses, disability worsening and cognition in the subgroup of patients with active SPMS, according to an analysis of the EXPAND extension cohort (Giovannoni et al. ECTRIMS 2020; abstract P0238). The annualized relapse rate was 0.08 with continuous siponimod for up to five years. Median time to 6-month CDP was not reached for the continuous group compared to 48 months for the group switched from placebo to siponimod. The risk of confirmed cognitive worsening was 33% lower in the continuous vs. switch group.
Can NfL replace MRI?
The Swiss MS cohort examined serum neurofilament-light (NfL) samples from 806 patients with RRMS, SPMS and PPMS who were relapse-free over a median 4.7-year follow-up (Lorscheider et al. ECTRIMS 2020; abstract P0154). A total of 19% had progression independent of relapses (PIRA). Baseline NfL level was associated with age and EDSS score. The risk of PIRA increased by 23.5% per 1 standard deviation higher baseline NfL z-score. Patients with PIRA had 11.6% higher baseline NfL level compared with stable patients. NfL levels decreased 10.8% during treatment with a monoclonal antibody DMT and 10.4% during treatment with an oral DMT compared to untreated patients.
A separate study suggested that periodic serum NfL could be used instead of annual MRIs in patients with clinically stable disease (Uher et al. ECTRIMS 2020; abstract P0175). The observational study compared annual NfL levels with MRI. Overall, 91% of patients with an active lesion in the preceding 6 months had serum NfL >30th percentile. Conversely, for patients with NfL < 30th percentile, only 14.3% had >1 active lesion and 4.8% had >2 active lesions in the preceding six months.
SPMS consensus guidelines
A panel of 15 Spanish neurologists have developed consensus guidelines on the diagnosis of SPMS (Oreja-Guevara et al. ECTRIMS 2020; abstract P0248). The group concluded that EDSS is the best method for defining progression; a worsening of 2 points in any functional system (except visual) suggests progression; >20% worsening in T25FW or 9HPT confirms progression in a patient with EDSS worsening; and a sustained change in brain atrophy suggests progression. The group agreed that a minimum time to confirm PIRA was 6 months. Annual assessments of cognitive change (SDMT, BRB-N or BICAMS), quality of life, depression and fatigue were recommended.
The Madrid MS Unit has reported the clinical experience of 41 COVID-19 patients with MS (Meca-Lallana et al. ECTRIMS 2020; abstract P0079). Mean age was 39.4 years; 51% were female; 93% had RRMS and 7% had PMS; mean MS duration was 9 years; and median EDSS score was 2.5. Patients were currently treated with oral agents (46%), MAbs (39%) and injectables (10%); 66% had received a prior DMT. Seventeen percent were admitted to hospital; no patient required ICU admission. Hospitalized patients tended to be older with a higher EDSS score. A total of 17% experienced worsening MS. DMT was delayed or discontinued in 10 patients. All patients had a good outcome following SARS-CoV-2 infection.
There has been conflicting opinion about the safety of B cell depletion during the COVID-19 pandemic. A case series examined SARS-CoV-2 antibodies in 11 MS patients (mean age 50.5 years) with proven/suspected COVID-19 (Wallach et al. ECTRIMS 2020; abstract P0923). A total of 7/11 were on an anti-CD20 MAb. All patients requiring admission for supplemental oxygen (n=4) were receiving an anti-CD20 MAb, raising concern that anti-CD20 therapy may be associated with an increased risk of acquiring or responding to COVID infection. All four hospitalized patients subsequently recovered. Additional information on the risk of SARS-CoV-2 infection with ocrelizumab is expected at the late-breaking session later this month.
Clinical tip of the day
Patient-reported disability scores on the Patient-Determined Disease Steps (PDDS) scale are very similar to clinician scores using the EDSS (Makin et al. ECTRIMS 2020; abstract P0026). PDDS scores range from 0 (no disability) to 8 (confined to bed) in 1-point increments. A U.S. prospective study found that a PDDS score of 0 (no disability) was comparable to EDSS 1.4; a PDDS score of 8 was comparable to EDSS 8.4. A previous study using a smaller sample size suggested PDDS 0 was equivalent to EDSS 2.9, with more comparable scores at higher levels of disability (Learmonth et al. BMC Neurol 2013;13:37). The results suggest that the PDDS may have some utility in assessing disability during a virtual visit.