Latest news from the European Committee for Treatment and Research in Multiple Sclerosis 2019

On September 11-13, 2019, the European Committee for Treatment and Research in Multiple Sclerosis (a conference known as ECTRIMS) held their 35^th Congress in Stockholm, Sweden. Nearly 10,000 researchers, clinicians, industry representatives and others gathered at ECTRIMS to share their knowledge and learn about the latest advances in MS research.

The three-day conference includes a scientific programme, educational sessions, plenary lectures; and hot topics, young investigator and poster sessions to share the latest MS research findings and promote discussion.

Over the last 20 years, there has been tremendous advances and growth in the MS field. In 1998, only 1,700 delegates attended ECTRIMS (versus nearly 10,000 in 2019), which at the time was an all-time high in terms of conference participation.

This year’s conference brought attention to major unmet needs in MS, specifically in the areas of risk factors and mechanisms of the disease, imaging, biomarkers, study design and novel treatment approaches.

An important theme of the conference was how the MS field can utilize real-world data collected from patient registries, health administrative databases, etc. in order to guide the future of MS treatment. Keynote speaker, Dr. Maria Trojano (University of Bari), shared how real-world data can be used to further our understanding of drug effectiveness, treatment strategies, factors that impact treatment response, safety, tolerability and pregnancy outcomes. To capitalize on this data, Dr. Trojano mentioned several initiatives now emerging to address and improve data quality (e.g. data standardization, data validation within data sets, data harmonization across data sets), and to develop new methods and approaches to understand the data (e.g., advanced statistical techniques).  By asking the right questions and employing the right methods, researchers aim to close gaps in our knowledge of MS.

Research Highlights:

• Phase 3 clinical trial results demonstrate that ofatumumab is an effective emerging treatment for relapsing-remitting MS

Dr. Stephen Hauser (University of California San Francisco) presented results from a phase III clinical trial (named ASCLEPIOS I and II) to examine the efficacy and safety of ofatumumab (Novartis) against teriflunomide (Aubagio®, Sanofi Genzyme) in people with relapsing-remitting MS. Ofatumumab, like rituximab and ocrelizumab, binds to CD20 on the surface of B cells, resulting in B cell depletion thereby reducing inflammation in the central nervous system. Ofatumumab is believed to have a stronger bond to CD20 and may be more active than existing drugs. Results from the phase 3 clinical trial demonstrate that ofatumumab maintains a favourable safety profile. As compared to teriflunomide, ofatumumab demonstrated significant reduction in annualized relapse rate by at least 50%, significant reduction in 3-month and 6-month confirmed disability progression, significant repression of gadolinium (Gd) lesions and reduction in the number of new and enlarging lesions. Altogether, this demonstrates profound suppression of inflammatory activity. Overall, the results indicate ofatumumab is considered a safe and efficacious treatment for relapsing-remitting multiple sclerosis.

• Treatment of natalizumab in pregnant women with MS reveals lower relapse rate during pregnancy and postpartum period

There is a lack of data to guide choices before, during and after pregnancy for women affected by MS, particularly around those with high disease activity. Dr. Doriana Landi (University of Rome Tor Vergata) and colleagues examined the annualized relapse rates in pregnant women taking natalizumab. In this study, researchers found that women who continued to take natalizumab during their pregnancy and in the postpartum period had a lower risk of relapse as compared to those that discontinued treatment before getting pregnant or those with an early interruption of treatment. Natalizumab treatment was not associated with any major adverse safety events in pregnancy and newborns. There was an occurrence of anaemia in newborns. A larger sample would be needed to further evaluate all fetal risks. Note: Use of any medication during pregnancy should be discussed with your physician/neurologist.

• Advances in stems cell therapy for MS

The use of autologous hematopoietic stem cells (AHSC) harvested and transplanted back into a person with MS following chemotherapy has been shown to be an effective treatment in a sub-set of people with highly active relapsing disease. Most people treated with AHSCs show no evidence of disease activity after one treatment (i.e. no new relapses, no new or active lesions detected by MRI) and some have demonstrated gain of function (refer to Canadian Bone Marrow Transplantation (BMT) Trial for more details).

In addition to AHSC, researchers are investigating the use of other types of stems cells, such as mesenchymal stem cells (MSC) that do not require chemotherapy.

• Dr. Antonio Uccelli (University of Genoa) presented preliminary results from an international multi-centre phase 2 clinical trial that evaluated the safety and clinical efficacy of MSC for the treatment of MS. The MS Society of Canada supported the Canadian arm of this study. MSC are adult stems cells that may have a potential benefit in neurodegenerative diseases, because of their ability to reduce inflammation and potentially protect myelin and boost repair. The international trial engaged 144 participants with relapsing-remitting and progressive forms of MS. The early data confirmed that the treatment was safe, however there was no significant changes in the reduction of active lesions in the treated group at 24 weeks (both were primary outcomes of the study). There was an observed trend of decreased relapses in the treatment group. Further data analysis will assess other clinical outcomes and repair of myelin. For more details refer here.

• Emerging biological markers of multiple sclerosis – Neurofilaments

Neurofilament light chain (NfL) are nerve cell-specific components that are believed to be a sign of neuron degeneration or damage. NfL can be detected in the blood in many neurological conditions and is an emerging biomarker for MS. A biomarker is a measurable indicator of a biological process that can be used as a predictor of health or disease.

• Dr. Ludwig Kappos (University Hospital Basel) presented data on NfL as an emerging biomarker and its link to relapses and progression in MS. Current evidence shows that NfL levels are not only raised during relapses, but also after recovery from the relapse.
  • Dr. Kathryn Fitzgerald (John Hopkins School of Medicine) presented data that showed that individuals with MS have elevated NfL associated with poorer neurologic function and greater levels of disability. Continued research on NfL will evaluate its use as a prognostic biomarker for MS

• Three new therapies emerging for Neuromyelitis Optica Spectrum Disorder (NMOSD)

Neuromyelitis Optica Spectrum Disorders (NMOSD) is a demyelinating neurological disorder affecting the optic nerves and spinal cord. While distinct from multiple sclerosis, both are inflammatory diseases of the central nervous system that are sometimes difficult to distinguish. Ninety percent of people with NMOSD have relapsing forms of the disease and continue to experience attacks and relapses. Currently, there is one Health Canada approved therapy for NMOSD and two other promising therapies in the pipeline:  (Health Canada approved eculizumab, and the emerging therapies are inebilizumab andsatralizumab).

• In the PREVENT study, eculizumab was administered in adults with NMOSD (those that tested positive for anti-aquaporin-4 in their blood). At 48 weeks, 97.9% of patients receiving the therapy were relapse free as compared to 63.2% of patients receiving the placebo. Patients receiving it as a monotherapy (no other therapies were taken) were 100% relapse free at 144 weeks. Trial participants also experienced improvements in quality of life, pain, disability and mobility. The most common side effects reported during the clinical trial were upper respiratory tract infection, headache, nasopharyngitis, and nausea. The eculizumab product monograph carries a black box warning of the risk of potentially fatal meningococcal disease; no cases of meningococcal infection were reported in the PREVENT clinical trial.
  • In the N-MOmentum clinical trial, inebilizumab was administered in adults with NMOSD (either those that tested positive or negative for anti-aquaporin-4 in their blood). In the anti-aquaporin-4 positive group, there was a 77.3% reduced risk of relapse, and in the total treatment group (positive or negative for aquaporin-4) showed a 72.8% reduction of risk of relapse. In addition, the treatment group experienced significant reductions in disability, hospitalizations, and lesions as seen on magnetic resonance imaging (MRI).
  • The SAkuraStar clinical trial tested satralizumab in adults (both anti-aquaporin-4 positive or negative) and demonstrated a significant reduction in the risk of relapse by 55% in the treatment group. Additionally, there was a 79% reduced risk of relapse in patients that are anti-AQP-4 positive.

These are just some of the late breaking and interesting research in MS.  

Browse all research presented at ECTRIMS  – here

To listen to ECTRIMS conference highlights go to the RealTalk MS podcast with Jon Strum – here  If you have a question or a comment, please share below.