2017 PNS Meeting GBS|CIDP Research Projects

The following research projects relating to GBS|CIDP were presented at the 2017 Peripheral Nerve Society Meeting in Sitges, Spain.

Filip Eftimov, MD, PhD
Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (ClDP) is a remarkably heterogeneous disorder with various clinical presentations. Despite different sets of diagnostic criteria , not all patients with treatable ClDP are identified. Several challenges remain during treatment, such as which treatment should be started first, when are patients adequately  treated and when can treatment be stopped. In other words, there is an unmet need to improve diagnostic criteria and find clinical or biological variables that can predict treatment response, disease activity and long-term outcome. To address
these questions, it is required to conduct a long-term prospective study with a large group of ClDP patients collecting
highly standardized data and biomaterials.
In recent years, several national registries and biobanks have been developed. However, even in large countries, these registries will not be able to include sufficient patients to address the most important challenges described above. Recently a multidisciplinary group of 24 people from 13 countries attended the European Neuromuscular Center (ENMC) workshop. Eight currently ongoing international ClDP registries that included a total of over 1300 patients were compared to assess infrastructure and collected clinical data, diagnostic data and biomaterials. During this workshop a consensus was reached on several important issues to make comparison between these registries possible. A central database (INCbase) will be used to upload data from current registries and databases while these registries continue to exist.
Next steps are to harmonize the current registries protocols and to set up INCbase. This global database is expected to be operational in 2018 and will collect data from thousands of ClDP patients to enable solving some of the important challenges in diagnosing and treatment of ClDP.

Towards an affordable treatment of GBS for patients from low-income countries
Badrul Islam, MD, PhD Fellow
icddr,b, Dhaka, Bangladesh, Erasmus MC, Rotterdam, The Netherlands

Guillain-Barré syndrome (GBS) takes its toll on the resource poor developing countries where the incidence of GBS is several fold higher than that of Europe and North America. In Bangladesh, 15% of patients with GBS die and 20% remain unable to walk. The poor outcome of GBS in these countries is explained predominantly by the lack of treatment and medical support. Specific treatment for GBS with either intravenous immunoglobulin (IVIG) or plasma exchange (PE) in Bangladesh can be afforded by a small minority of patients and more than 90% of patients receives only supportive care.
Our aim was to develop a safe and effective treatment for patients who cannot afford the expensive IVlg or PE. We developed a new technique that is based on the same principle as PE, removal of neurotoxic antibodies and other components from the blood, but is 25 times less expensive. In this Small Volume Plasma Exchange (SVPE) blood is obtained from patients and cleared from the plasma just by gravity. This procedure can be done by the bedside of the patient, without the use of electricity and complex machinery. We started with a pilot study to define the feasibility and safety of the procedure using a strict protocol in 20 patients with GBS in the National Institute of Neurosciences and Hospital in Dhaka, Bangladesh. This study showed that the procedure indeed is feasible and safe during a follow-up of 6 months. We are very thankful to the GBSICIDP Foundation International for funding part of this study. Based on this study we cannot conclude on the efficacy of the treatment that needs to be defined in a new study in a larger number of patients. To conduct this efficacy study, further funding is required. If the efficacy is demonstrated, SVPE may become available to treat GBS in patients from low-income countries that are currently untreated. About more than half of all patients with GBS in the world belong to this category.

Marielle Pruooers
Universitv Medical Center Maastrict, The Netherlands
IgM paraprotein associated polyneuropathy is a slowly progressive disease with numbness or tingling of arms and legs and severe imbalance. Occasionally, tremors and weakness are present. These symptoms are disabling, but difficult to measure. In addition, the disease is relatively rare, not very well-known, and there is no cure available. The IMAGiNe study aims to gather more knowledge about the disease by creating an international database of a large group of patients. From these patients we will learn more about the history of the disease, neurological and hematological disease characteristics, and the response to current or past treatments. The IMAGiNe study will also evaluate current outcome measures and develop new outcome measures, hereby focussing on patients’ needs. These outcome measures will represent the impairments, disabilities, quality of life and treatment expectations. The study has started in the Netherlands in 2016, and currently 90 patients are included. In 2017 the study will also be performed in the United Kingdom, Spain, Serbia, Italy, France, Switzerland, and the United States of America, aiming to include at least 400 patients worldwide. The knowledge gained from the IMAGiNe study will serve as a starting point for new therapeutic trials in the near future.

A new treatment with compliment inhibition improves motor function in Guillain-Barré Syndrome: Japanese eculizumab trial for Guillain-Barré Syndrome (JETGBS)
Satoshi Kuwabara
Department of Neurology, Chiba University Hospital, Chiba, Japan
Recent basic studies on the pathophysiology of Guillain-Barré syndrome (GBS) have shown that complement activation has a major role on peripheral nerve damage in GBS. Eculizumab (Alexion Pharmaceuticals Inc) is a humanized monoclonal antibody against complement C5, and is approved to treat complement-mediated blood diseases. At the Peripheral Nerve Society Congress (8-12 July 2017, Sitges, Spain), Japanese GBS study group presented results of a randomized placebo-controlled phase 2 trial with eculizumab in patients with severe GBS (unable to walk). At 24 weeks, marked improvement in motor function was observed in patients treated with eculizumab; 74% of patients in the eculizumab group (n=23) regained ability to run , compared with 15% in the placebo group (N=11).

A dose response trial of IV immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)/DRIP study
Professor K. Kuitwaard
Erasmus MC, University Medical Center, Rotterdam, The Netherlands
In clinical practice ClDP patients are treated with several dosages of intravenous immunoglobulin (IVlg) as well as with different intervals. It has never been investigated what the optimum dosage and frequency of IVlg in ClDP is. The effective component of IVlg is IgG. More frequent dosing will lead to more stable IgG levels in the blood as well as higher trough levels (the level directly before the next dose) which may lead to an improvement in muscle strength. Furthermore, more frequent dosing will lead to lower peak levels (the highest level in the blood) which may lead to less side effects.
It has never been investigated whether high frequency low dosage IVlg treatment is more effective than low frequency high dosage. In the DRIP study we investigate if:
1. A more frequent infusion at a lower dosage is more effective in ClDP.
2. A more frequent infusion at a lower dosage leads to less side-effects.
3. A more frequent infusion at a lower dosage leads to more stable blood levels.
It has been shown that a lot of ClDP patients are still receiving immunoglobulins even though they do not need treatment any longer. Therefore we will check before the start of the study whether patients still need IVlg treatment.

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