In 2017, a nationwide survey of US CIDP patients was conducted to assess the impact of disease-related disability and treatment on lifestyle and work activities. Approximately 3250 individuals aged ≥18 years, recruited by the GBS|CIDP Foundation and self-reported to have CIDP, were invited to complete an online survey; of these, 475 completed the survey and their responses were used to assess disease and treatment burden.
No better way to show you care for rare.
This Rare Disease Day (February 28), the GBS|CIDP Foundation will be launching an online Patient Registry for patients with GBS|CIDP or variants of the condition. The GBS|CIDP Patient Registry, consisting of patient reported surveys & questionnaires, will allow healthcare professionals access to critical, de-identified patient data, while pursuing medical advancements and developing patient resources. It will be hosted in partnership with the National Organization for Rare Disorders (NORD); an independent non-profit patient advocacy organization dedicated to individuals with rare diseases and the organizations who serve them. Studies of these conditions may take years to finish, but patient reported registries provide power in numbers! The Foundation will provide periodic updates and results with the discoveries made possible with this impactful data.
On this Rare Disease Day, and beyond…if you are a patient, or represent a patient living with GBS, CIDP or a variant of the condition, we encourage you to enroll in GBS|CIDP patient registry and show you care for rare!
By Jeffrey A. Allen, MD
Member, GBS|CIDP Foundation Global Medical Advisory Board
CIDP as a named disease entity is now about 4 decades old. The laboratory data that helps define the disease, nerve conduction studies and in some cases cerebral spinal fluid and nerve biopsy, is even older; and the initial description of what has now come to be known as CIDP was probably first published well over 100 years ago. CIDP evidence based treatments, corticosteroids, IVIG, and plasma exchange, have been known to be effective since the 1980’s and 1990’s. In 2018 progress of CIDP research can seem… stagnant.
And yet, despite appearances, scientific achievements within the field are unquestionable. Physicians and scientists from around the world have passionately engaged all aspects of the disease from the most fundamental immunologic derangements to better defining the clinical spectrum of CIDP to exploration of new CIDP treatment options. Thus far in 2018 over 140 CIDP papers have been published in peer reviewed medical journals1. The publication growth by decade, reflective of intellectual curiosity, has been steadfast. In 1990 a total of 31 papers were published, followed by 84 in 2000, and 107 in 2010. Just in the last several years we have learned that about 10% of those with CIDP harbor one of two autoantibodies called neurofascin 155 or contactin 1. These antibodies target a specific portion of peripheral nerve and may have important treatment implications. We’ve learned the challenges that are encountered when diagnosing CIDP, and have a better understanding on how to avoid diagnostic pitfalls. From a treatment perspective we have very recently learned that subcutaneous immunoglobulin (SCIG) is safe and effective for CIDP maintenance therapy, but that unfortunately the immunomodulating medication fingolimod does not have a role in CIDP treatment. While certainly not comprehensive of all that has been learned over the last couple years, it is examples like this that offer insight into the progress being made and what direction the field is headed. That direction is one of a greater understanding of what makes one person’s CIDP different than the next. What is the underlying immunologic problem, and what does that tell us about the diagnosis, prognosis, and treatment of any individual person.
Around the world there are currently a multitude of studies that are exploring ways to get more out of our current CIDP treatments. These studies include the ProCID and DRIP studies, largely being conducted in Europe, which will help us better understand how IVIg dose and administration frequency influence efficacy. In the Netherlands the ongoing IOC trial will help us understand how often remission occurs in CIDP. The GRIPPER study conducted in the US may shed insight on how CIDP symptoms fluctuate in between IVIg infusions. Each of these studies anticipates conclusion in 2018 or 2019. Collectively they will inform us on how to personalize IVIg treatment: how to get more out of the treatment for those that need it, and how to get patients off treatment if it is no longer needed. Looking farther out, the OPTIC trial conducted in the Netherlands and UK will explore the roll of combining IVIG treatment with corticosteroids. This trial is expected to conclude in 2023.
Equal to better understanding how to improve our current treatment protocols is identification of new treatment options. There are many many ways to suppress or manipulate the immune system. While some of these interventions may achieve the desired result of suppressing the inflammatory attack on nerves affected by CIDP, the risk of aggressive immunosuppression can be substantial and unnecessary. The goal is to maximize efficacy while at the same time minimize risk, with escalation of risk proportional to disease severity and prior treatment history. One line of treatment that has fostered some degree of enthusiasm is that of B cell depletion therapy with rituximab. A randomized controlled trial of rituximab in CIDP is currently underway in Italian centers. US physicians have expressed similar interest in exploring this treatment pathway, and a clinical trial of B cell depletion at US centers is currently in development. While the role of B cell depletion in the treatment of CIDP is presently unknown, the hope is that these trials will help us learn which groups of patients within the broader context of CIDP might benefit from rituximab or similar medications. The hope also is to understand how these interventions can be tailored to individual patients such that unnecessary risks can be avoided.
In 2019, patients with CIDP throughout the world can anticipate initiation of a CIDP study that will be known as INCbase. INCbase will not explore a specific treatment or intervention in CIDP, but rather is a registry designed to learn more about those affected by the disease. One of the challenges of finding treatments in CIDP is the realization that CIDP has many faces, and those faces may be mediated by different immunologic insults. The objective of INCbase is to better understand what defines the faces of CIDP. What symptoms constitute the clinical boundaries of CIDP? What testing is helpful in the diagnosis? Why do some treatments help some people, but not others? How does the pathophysiology of the disease differ from patient to patient? Participants in INCbase will simply be asked a series of standardized questions and have a standardized series of metrics collected, such as grip strength. In some cases blood may be collected as well. Participants will be followed on a periodic basis over a couple years. Ultimately this information will be critical in the development of treatment protocols that are specific to any individual patient, at any given stage of their disease.
While many of us, patients and clinicians alike, yearn for an escalated pace of progress in the field of CIDP, the knowledge gathered even within just the last several years is undeniable. We are all in debt to those affected by CIDP that participate in the research that helps advance the field forward. Patients interested in research participation are encouraged to talk to their doctor about programs that might be locally available. Physicians at GBS/CIDP Centers of Excellence can be particular helpful in this regard. The field is trending toward personalization of therapy, whether that be by getting more out of our currently available interventions or by discovering which patients might be candidates for different treatment options that are both effective and safe. A better understanding of the clinical and laboratory boundaries that define CIDP and how individual patients under the CIDP umbrella differ will add immensely to treatment personalization. We all eagerly await the results of actively enrolling CIDP trials and look forward to initiation of new studies, such as INCbase, identification of new novel antibodies, and clinical trials of B cell depletion therapy. Collectively these studies have the capacity to change the landscape of CIDP management in ways unknown in the not too distant past. We are making progress.
- Pubmed search of “chronic inflammatory demyelinating polyneuropathy OR CIDP” accessed on 10/5/2018.
David Saperstein, MD
Co-Director GBS/CIDP Center of Excellence
Phoenix Neurological Associates
Intravenous immunoglobulin (IVIg) is one of the main therapies used to treat CIDP. This therapy can be very effective but there are drawbacks. Some people experience headaches related to the intravenous infusions. Some people have difficulty with IV access. Also, the need for IV infusions lasting several hours one or more days every month can prove burdensome with respect to work or travel. In recent years there has been growing interest in infusing immunoglobulin through the skin in a process called subcutaneous administration (subcutaneous immunoglobulin, or SCIg). SCIg is commonly used in patients with immunodeficiency. SCIg is administered by patients themselves at home. Infusions are generally given in the fat under the skin in the stomach or thighs. Over the last few years there have been small studies of SCIg in patients with CIDP. It has become a popular strategy for treating CIDP in Europe and has been used in some patients in the United States. Several brands of IVIg can be given subcutaneously, but there are a couple of products made specifically for subcutaneous administration. These are 20% in concentration, in contrast to most IVIg products which are 10%. The more concentrated 20% products allow infusions to be completed in just a couple of hours one or two days each week. Unlike IVIg which is usually given in a big dose several weeks apart, SCIg must be administered every week).
The FDA recently approved a 20% formulation of SCIg called Hizentra for maintenance treatment of CIDP. This is based on the results of a large international study of Hizentra called the PATH study (for polyneuropathy and treatment with Hizentra). One hundred and seventy-two patients from North America, Europe, and Asia were studied. These were all patients who were receiving regular maintenance treatment with IVIg. To be eligible to participate in the PATH study, patients had to demonstrate that they needed regular treatment with IVIg. This required them to come off of IVIg and display objective worsening within 12 weeks. Of 245 patients taken off of IVIg, all but 28 worsened within 12 weeks. Ultimately, 172 patients were enrolled. 57 received low dose SCIg (0.2 grams per kilogram per week), 58 received high dose SCIg (0.4 grams per kilogram per week) and 57 received placebo (albumin protein solution). The patients were watched closely over the next 6 months. The main outcome was to see how many patients in each group worsened. Since each patient in the study had already shown that they worsened when coming off of regular IVIg treatments it was assumed that most of the patients in the placebo group would worsen. Interestingly, only 63% did. It is not clear why more did not. Nevertheless, many more patients in the placebo group relapsed over 6 months compared to patients who got SCIg (39% in the low dose group and 33% in the high dose group). Both dose groups did significantly better than placebo, but there was no significant difference between the low and high dose groups. Not surprisingly, the patients receiving SCIg had more skin irritation than patients getting placebo (19% in the low dose group, 29% in the high dose group and 7% in the placebo group). However, much fewer patients experienced reactions to Hizentra than they did to IVIg.
Approximately 90% of subjects rated the SCIg injection process as being easy to learn. About 53% of patients receiving SCIg preferred this treatment to IVIg, citing increased independence and less side effects.
Anybody with CIDP currently receiving IVIg could potentially be switched to SCIg. Of course, if the IVIg is working fine there is no reason to change anything. SCIg is a particularly appealing option for patients who get side-effects such and headaches or nausea from IVIg, who have trouble with IV access, or who prefer to have control of their treatment. Another advantage of SCIg is that it can be stored at room temperature, so people can easily take it with them if they are travelling.
Research is critical to serving the cause and the community. The GBS-CIDP Foundation International believes in supporting research by funding grants for projects that contribute to the knowledge and advancement of treatment of GBS|CIDP and variants of the condition.
We are pleased to announce our 2018 Research Grant Awardees are as follows:
1. Principal Investigator: Elisabetta Babetto, Ph.D., Research Assistant Professor
The Research Foundation for SUNY on behalf of U. at Buffalo
Project: “Targeting Wallerian-like degeneration in GBS mouse models”
Synopsis: Axon degeneration accounts for the most debilitating clinical symptoms of Guillain Barré Syndrome (GBS). Our goal is to explore the mechanisms of axon loss in this condition, by testing the hypothesis that axon degeneration in GBS is governed by a defined molecular program amenable for therapeutic intervention. Specifically we will test whether inactivation of proteins, known to dictate axon loss after experimental injury, affords axon terminal protection in murine models of GBS.
2. Principal Investigators: Luana Benedetti, MD, PhD and Lucilla Nobbio, PhD
University of Genova, ITALY
Project: Sphingomyelin dosage in GBS/CIDP patients: biomarker validation in a multicenter, prospective study
Synopsis: The identification of a biomarker specific and sensitive to improve diagnostic accuracy, to monitor disease activity, to stage patients, and to select specific treatments is a prime goal for the GBS/CIDP Community. Due to the encouraging results we obtained by dosing SM levels in the CSF of patients affected by GBS and CIDP, we propose the present study whose major significance is to validate our results on a sizeable and carefully selected number of patients.
3. Principal Investigator: Paolo Ripellino, MD, Neurologist
Neurocenter of Southern Switzerland
Project: (IGOS) in Switzerland: a deeper look into HEV-induced GBS
Synopsis: This study will increase the amount of clinical and prognostic data of the IGOS consortium with the inclusion of patients from an important area located in the middle of Europe. The high quality of the Swiss health care system will allow researchers to obtain accurate data. The systematic collection of acute phase samples in a biobank will be fundamental for future international, cooperative studies. The subproject about the role of HEV is innovative because – although so far neglected – HEV is an increasing, preventable (by appropriate cooking and blood donors testing) disease and this infection is associated to GBS.
4. Principal Investigator: Luis Querol MD PhD
Hospital de la Santa Creu i Sant Pau, Barcelona
Project: Disease-specific Biomarkers In Inflammatory Neuropathies
Synopsis: Inflammatory neuropathies (IN) are disorders in which disease-specific biomarkers are not required or diagnostic purposes, leading to disease heterogeneity. We discovered the association of anti-contactin-1 antibodies to a specific CIDP subset using an unbiased approach. This strategy has also proven effective in antibodies against NF155 and nodal neurofascins in CIDP, in which our group has also played a central role. The discovery of paranodal antibodies hasboosted translational research in the field, including the description of specific pathology, genetic background (DRB1*15 association with NF155 antibodies), response to treatment and animal models, supporting the idea that the classification of IN according to disease-specific biomarkers would make IN research and care more efficient.
5. Principal Investigator: Dr Laura Zambreanu, MD, MRCP
National Hospital for Neurology and Neurosurgery, UK
Project: Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in CIDP (OPTIC trial)
Synopsis: Most CIDP patients are treated with regular intravenous immunoglobulin (IVIg) because of fast improvement and rare adverse events, but IVIg is expensive. Corticosteroid treatment is associated with longer time to improvement and more side effects, but may lead to long-term remission1,2. We intend to participate in a multicentre, randomized, double-blind, placebo-controlled superiority trial in patients with active CIDP. The primary objective is to assess whether combining IVIg and intravenous methylprednisolone (IVMP) leads to more frequent long-term remission in CIDP compared to IVIg alone. Patients will be recruited in the Netherlands and the UK.
Congratulations to all and thank you for your continued commitment to research in the area of GBS|CIDP and variants of the condition.