Review: MS PARIS 2017, the joint ECTRIMS/ACTRIMS Meeting

The 7^th joint ECTRIMS/ ACTRIMS conference (#MSParis2017), held this year in Palais de Congress in Paris, just closed its doors after 4 days of exciting clinical and research advancements. With more than 10,000 delegates and 3978 abstracts, this was the largest conference in Multiple Sclerosis so far.

The programme was full, starting on Wednesday 25^th of October with a day aimed at registrars and junior consultants including 18 teaching courses on clinically salient topics across the whole of the MS spectrum, as well as two “Nurses sessions,” emphasising the important of MS Specialty Nursing both for clinical outcomes and research advancements.

The main conference started the following day with an unexpected cabaret performance, followed by a lecture by Dr Hans Lassman, University of Vienna, that succinctly explained the advances made in clarifying the pathophysiology of this inflammatory disorder, the insights into the phenotype of brain infiltration by T and B lymphocytes, the clinical implications of these findings and further questions for research.

Over the next 3 days, during the 25 parallel sessions, more than 2000 posters and multiple sponsored symposia, we heard about clinical and scientific advances in adult and paediatric MS, as well as other demyelinating conditions such as Neuromyelitis Optica spectrum disorders. The most important findings presented at this year’s ECTRIMS/ACTRIMS meeting, that will imminently affect clinical practice are:

The 2017 Revision of the McDonald Criteria

The 2017 Revision of the McDonald Criteria were presented by Jeffrey Cohen, Cleveland Clinic in one of the most well-attended sessions, followed by an in-depth presentation of the implications of the new criteria for clinicians by Jeremy Chataway, National Hospital for Neurology and Neurosurgery. The main changes in the criteria are:

• In patients with a typical Clinical Isolated Syndrome and fulfilment of the Dissemination in Space (DIS) criteria, the presence of oligoclonal bands (OCBs) can now support the diagnosis of MS. This may cause a key change in current clinical practice for many.
• Cortical lesions are included in the Dissemination in Time (DIT) criteria.
• ‎Primary progressive MS criteria have remained the same but also now include cortical lesions.
• No distinction is made between symptomatic and non-symptomatic lesions.

Advancements in the treatment of Progressive MS

“We can treat progressive disease although results have been modest so far;” this was an encouraging theme throughout the meeting, with many presentations highlighting the emergence of new data to support the emergence of treatment options soon for a previously untreatable condition.

Ocrelizumab (ORATORIO study):

Humanised monoclonal anti CD20 antibody.

This was the first positive phase 3 clinical trial in Primary Progressive MS showing that Ocrelizumab is reducing disability progression in SPMS. An open label extension trial was recently completed showing that ocrelizumab effect is sustained with ongoing treatment. The benefit of DMTs in older patients may be reduced, particularly in progressive MS.

Siponimod (EXPAND trial):

Selective modulator of Sphingosine 1 Phosphate receptor.

Significantly delayed disability progression by 26% in 6 months in patients with Secondary Progressive MS. Siponimod also reduced MRI disease activity and brain volume loss at 12 and 24 months.

Ibudilast (SPRINT- MS trial):

Phosphodiesterase and macrophage inhibitory factor inhibitor.

Initial data showed that ibudilast slowed the progression of brain atrophy in progressive MS (both primary and secondary).

Natalizumab improving upper limb function in SPMS:

Although not improved EDSS or lower limb function, natalizumab led to improvement in upper limb function (9hole peg test) in SPMS patients.

Future Pipeline:

Progressive MS is an active research area with many ongoing trials including MS STAT2, SPI2, MS SMART as well as new molecules such as Laquinimod, Mastinib (tyrosine kinase inhibitor), Ibudilast and Idebenone.

New treatment options for Relapsing Remitting MS:

Ozanimod (RADIANCE trial):

Highly selective Sphingosine 1 Phosphate receptor agonist.

In a multicentre, randomised, double blind trial examining ozanimod versus interferon in patients with active disease, ozanimod was found to have a 38% reduction in annual relapse rate over 3 years compared to interferon.

In addition, secondary endpoints were met, including reduction in the number of T2 lesions and reduction in total brain volume loss and grey matter volume loss at 2 years. Although there were some cardiac effects, these were relatively mild.

Opicinumab (SYNERGY trial):

Anti lingo 1 monoclonal antibody.

SYNERGY assessed the efficacy of opicinumab in patients with relapsing MS as an add on therapy to interferons. The post-hoc analysis of SYNERGY data presented in the conference, indicated an increased effect of opicinumab versus placebo (when used at the same time as interferon) in patients with shorter disease duration and lower rates of Magnetisation transfer ratio (MTR) in MRI suggestive of lower myelin content.

Biogen announced the initiation of a phase 2 double blinded control study (AFFINITY) to further study the effect of opicinumab in these patients.

Ocrelizumab improving visual function in relapsing MS (OPERA studies):

Ocrelizumab was associated with a significant improvement in visual outcomes at 12 weeks in RRMS patients compared to interferons.

Need for early treatment to prevent progression:

Will Brown from University of Cambridge in a plenary session, as well as A. Fabiatos from Melbourne, winner of a poster award, both presented data from MSBase, on the risk of secondary progression and the effect of Disease Modifying Therapies (DMT).

Improving disability trajectory was associated with a decreased risk of SPMS whilst greater level of disability, trajectory and age was associated with a higher risk.

Patients on all included treatments (injectables, figoolimod, natalizumab and alemtuzumab) showed reduced risk of conversion to SPMS compared with untreated patients.

The risk reduction was higher in most effective therapies (natalizumab/alemtuzumab) than injectables (HR: 0.65).

Treatment within 5 years of the first relapse was associated with significant delay in the time to progression compared to later treatments. Longer duration of therapy was associated with decreased risk of SPMS.

These results highlighted the importance of early diagnosis and early DMT.

Finally, DMT has an impact on mortality: An international population based study presented as a poster by E. Kingwell showed that exposure to interferons was associated with reduced all-cause mortality rates in patients with MS.

Overall, the 7^th ECTRIMS/ACTRIMS meeting this year highlighted the extraordinary advancements in this field of neurology both in terms of mechanistic insights and therapeutics. Most importantly, it brought together clinicians from across the globe in a beautiful venue, promoting further discussion and collaborations.

The 8^th ECTRIMS meeting will be held in Berlin, Germany on the 10^th-12^th October 2018 with hopefully even more exciting discoveries!