9th Joint ECTRIMS-ACTRIMS meeting – 11-13 October 2023

The following summarizes some of the highlights from Day 2 of ECTRIMS-ACTRIMS 2023.

October 13 Edition
October 11 Edition

Relapses common with drug de-escalation
Comparing high-efficacy DMTs
NEDA rethink
Does antiretroviral therapy lower MS risk?
Emerging concepts: cognitive PIRA
Lower use of high-efficacy DMTs in rural Canada
Clinical tip of the day

CONGRESS HIGHLIGHTS – THURSDAY EDITION

Relapses common with drug de-escalation
Almost one-half of patients who de-escalated treatment required re-escalation, according to an analysis of the Danish MS Registry (Elberling et al. ECTRIMS/ACTRIMS 2023;O098). The study examined 316 patients (mean age 45 years) who switched from a higher-efficacy therapy (primarily fingolimod and natalizumab) to a modest-efficacy agent. At 1.9-year follow-up, 46.5% of patients had re-escalated (73.5% due to disease activity), 25.9% remained on a modest-efficacy drug, 16.8% had made a lateral switch and 10.8% had stopped treatment. After de-escalation, 40.8% had a relapse or new T2 lesion and 21.5% had EDSS worsening. There was a lower risk of a recurrence of disease activity with age, suggesting that de-escalation may be appropriate in some older patients.

Comparing high-efficacy DMTs
Two studies reported a variety of methods to indirectly compare the efficacy of DMTs in RMS. The first study conducted a propensity score analysis of data from the ASCLEPIOS I/II trials of ofatumumab and the FREEDOMS I/II and TRANSFORMS trials of fingolimod (Butzkueven et al. ECTRIMS/ACTRIMS 2023;P755). Ofatumumab was superior to fingolimod with respect to annualized relapse rate (rate ratio 0.60) and time to three-month confirmed disability progression (CDP) (hazard ratio 0.54). A simulated-treatment analysis found that ofatumumab was also superior to cladribine and ozanimod on ARR and three-month CDP. A network analysis by the same group showed that ofatumumab, ocrelizumab, natalizumab and alemtuzumab were superior to cladribine and S1P receptor agonists. The authors concluded that MAbs have greater efficacy than oral DMTs.

Results were similar in an MSBase study comparing cladribine with fingolimod and MAbs in 3,064 MS patients (Roos et al. ECTRIMS/ACTRIMS 2023;P731). ARR was lower with cladribine vs. fingolimod (0.07 vs. 0.12) but higher with cladribine vs. natalizumab (0.10 vs. 0.06), ocrelizumab (0.09 vs. 0.05) or alemtuzumab (0.04 vs. 0.013). The effect on disability worsening was similar for cladribine, fingolimod and alemtuzumab, but ocrelizumab and natalizumab were superior to cladribine. The researchers concluded that cladribine is more effective than fingolimod but less effective than MAbs.

NEDA rethink
No evidence of disease activity (NEDA), defined as no relapses, new MRI lesions or disability progression, does not adequately capture functional changes in MS patients, according to a new two-year study (Solaro et al. ECTRIMS/ACTRIMS 2023;P1162). A total of 57 patients (mean age 39 years; mean EDSS 1.4) were stratified according to NEDA status. Overall, 24 of 25 patients in the NEDA group showed impairment on at least one domain of functioning over a two-year period. The proportion of patients showing some degree of worsening was 48% on the 6-Minute Walking Test, the Timed 25-Foot Walk and the Symbol Digit Modalities Test, 44% on the Fatigue Severity Scale and >50% on cognitive tests. Many patients in the no-NEDA group experienced clinical improvements despite ongoing disease activity.

Does antiretroviral therapy lower MS risk?
A number of case reports have suggested that the risk of MS is lower in HIV patients treated with antiretroviral therapy (ART). The putative mechanism is suppression of human endogenous retroviruses (HERV), which have been implicated in the pathogenesis of MS. Health data from British Columbia and Sweden were analysed to determine the rate of MS in HIV patients exposed to ART (n=21,614) compared to the general population (>6 million) over a 17-28-year period (McKay et al. ECTRIMS/ACTRIMS 2023;P049). The standardized incidence ratio (SIR) for MS was 0.55 for the ART-exposed HIV group. The rate of MS after exposure to ART was lower (SIR 0.25) for women. The authors concluded that ART may have a protective effect against the development of MS. In the phase II INSPIRE study of the ART raltegravir, treatment had no significant effect on Gd+ lesions, disability outcomes or quality of life (Gold et al. Mult Scler Relat Disord 2018:24:123-128). It has not been determined if a different ART or a combination of agents would be more effective in slowing the MS disease process.

Emerging concepts: cognitive PIRA
The concept of progression independent of relapse activity (PIRA) has been applied to cognitive change in a retrospective U.S. study (Fuchs et al. ECTRIMS/ACTRIMS 2023;O041). Cognitive worsening was defined as one standard deviation decline from the previous time point. Patients who were relapse free during that period and in the 9 months before or after cognitive worsening were considered to have cognitive PIRA. During the 15-year observation period, cognitive decline events were seen in 51.3%. Of these, 85.9% were PIRA and 14.1% were considered relapse-associated worsening (RAW). In the subset with EDSS assessments, 72.2% of worsening EDSS events were PIRA; 39.7% of cognitive PIRA occurred during periods without a corresponding EDSS-PIRA.

Lower use of high-efficacy DMTs in rural Canada
An analysis of health data in Alberta reported that MS patients in a rural setting started disease-modifying therapy later than patients in urban centres (Balcom et al. ECTRIMS/ACTRIMS 2023;P045). Rural patients were also less likely to receive a high-efficacy DMT. In the full cohort (N=4593), a higher proportion of patients from urban centres (42% vs. 37% for rural) or who were socioeconomically privileged (46% vs. 37% for deprived) had taken >1 DMT at one year. Urban patients were also less likely to have been prescribed a platform therapy (67% vs. 76%) and more likely to receive a high-efficacy DMT (40% vs. 33%). The authors noted that greater effort is needed to provide equitable access to DMTs regardless of the treatment setting.

Clinical tip of the day
About 1 in 4 CIS/MS patients will have an adequate response to a platform therapy (injectables, teriflunomide, dimethyl fumarate, azathioprine), according to an analysis of the Italian MS Registry (Addazio et al. ECTRIMS/ACTRIMS 2023;P730). Over a 15-year period, 26.9% were considered optimal responders, 28.5% experienced disability worsening and 44.6% were switched to a high-efficacy DMT.

October 13 Edition
October 11 Edition