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.
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.
For Rogers, this year has been filled with pain and triumph, a year of repetitive setbacks and remarkable progress. In August 2017, Rogers was paralyzed by a rare autoimmune condition, known as CIDP. Her first steps — at first with the assist of a harness — came a month later. Read more in Chicago Tribune. This Sunday, October 7, she will be running the 26.2 mile Chicago Marathon, and raising funds for the GBS|CIDP Foundation International.
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.
The Food and Drug Administration granted marketing clearance Friday for Hizentra, a treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) developed by CSL Behring. Lisa Butler, executive director of the GBS/CIDP Foundation International, said “The approval of Hizentra offers patients who were once burdened by traveling to the infusion center or hospital the flexibility to self-administer their treatment at a time, place, and on a schedule that’s convenient for them.”