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.