Chronic inflammatory demyelinating polyneuropathy, or CIDP, is a rare autoimmune disease that can cause severe numbness, weakness and disability. In a recent interview hosted by Sanofi, Dr. Jeffrey Allen, a neurologist and neuromuscular specialist at the University of Minnesota, discussed new efforts to standardize how clinicians define progression, relapse and treatment response in CIDP. He said the shared definitions, developed with input from researchers and patient advocates, will improve doctor-patient communication and make clinical trial data easier to compare.
Allen stressed that patient voices were critical in shaping the new language, particularly in how the term “refractory” was defined. Rather than suggesting no hope for improvement, the term now reflects a lack of response to one treatment while leaving the door open for others. He also pointed to emerging research on inflammation, the complement system and potential biomarkers that could help track disease activity. With nearly one-third of patients not responding to existing therapies and many others experiencing only partial benefit, Allen said there is an urgent need for new treatment options. Watch the full interview to hear more about what could redefine the future of CIDP care.
Alex Seluzhytsky:
Hello, my name is Alex Seluzhytsky. And I’m a Senior Global Medical Director at Sanofi. Today I have a pleasure of interviewing Dr. Jeffrey Allen on redefining possibilities in refractory CIDP. Welcome, Dr. Allen. And would you mind giving us a bit of your background and your professional experience in the field?
Dr. Jeffrey Allen:
Sure. Thanks, Alex. Thanks for having me as part of this conversation. I’m Jeff Allen. I’m a neurologist, neuromuscular specialist at the University of Minnesota. I have a very special interest in autoimmune and inflammatory nerve and muscle conditions, especially the immune mediated neuropathies, including CIDP. I’m an [inaudible 00:00:40] scientist, but I do a lot of clinical research trying to find better ways to diagnose and treat these rare immune neuropathies.
Alex Seluzhytsky:
Thank you. To ground us in today’s conversation, can you start by defining chronic inflammatory demyelinating polyneuropathy or CIDP? What is it?
Dr. Jeffrey Allen:
Yeah, sure. This is an autoimmune disease that goes after the peripheral nerves, so not the brain, not the spinal cord, but the peripheral nerves. And the result of this attack on the peripheral nerves leaves people with numbness and weakness, usually in the arms and legs. There can be quite a bit of variability in how it affects different people, but the typical way that affects somebody is that they develop numbness and sensory loss, usually in the feet and hands. Weakness follows in the legs and the arms. This impairs one’s ability to walk and the one’s ability to use their hands to manipulate their environment. The severity can be quite broad, but at least half of people the disease progresses to the point where you can’t live an independent existence without the help of somebody else. So it can really, really impact somebody’s quality of life.
Alex Seluzhytsky:
Shift our gears more into the clinical terms and definitions. The GPS and CIDP Foundation, a global non-profit supporting individuals and families living with autoimmune neuropathies presented redefined clinical terms in CIDP at recent conference. What prompted this initiative and what does it mean for the community?
Dr. Jeffrey Allen:
Well, one challenge that we’ve found over the last several years, several decades, is that the way we think about the change that this disease has on somebody’s quality of life and how we measure that change, it’s defined differently between different clinicians and different patients within clinical trials, and then other regulatory bodies also look at these definitions differently. And that lack of a unified definition of what it means to progress with the disease or respond to a treatment or to relapse, makes it really difficult to compare different outcomes in trials and to have an effective communication or dialogue with the patient to say, this is what we’re looking for a treatment. These are expectations for treatment, or how to monitor that change over time. So that was really an unmet need in the space and we felt that it’s really important to have a group of people come together to really decide what these key definitions mean.
Alex Seluzhytsky:
It’s a great initiative. And how might these definitions affect how the healthcare community diagnoses, documents, and treats CIDP in clinical practice? What are the implications for research?
Dr. Jeffrey Allen:
So probably not on the diagnosis side, but really where the impact’s going to come is to have a well-thought conversation with a patient on what the future looks like. So you have a new diagnosis, you start a treatment, what are expectations for that treatment? How do we find improvement after the treatment starts? How do we find improvement that maybe is inadequate after the treatment starts, and maybe meaning that you need to move on to a different treatment can help us to better understand what a relapse might look like or how worsening changes over time.
So it’s that uniform definition of between patients and clinicians so that we can all talk the same language is really, really important for these definitions. And from the clinical research side, just as important, but a little bit in a different way where now we can look at different trials that use the same definition for improvement, for example, and say, this is what one trial said is improvement, and now we can maybe have a similar definition for another trial instead of trying to piece together different definitions from different trials. So that uniform language is going to be really important for clinical trials as well.
Alex Seluzhytsky:
Okay. So let’s now maybe dig deeper into the refractory disease. As part of this initiative, the term refractory was defined as, and I apologize, I have to read this, “Absence of minimal response or relapse leading to or requirement treatment discontinuation after adequate dosing and duration of the administered therapy.” So quite a mouthful here. Based on your clinical experience, what does refractory look like for people living with CIDP that you see and treat?
Dr. Jeffrey Allen:
When we were developing these definitions, it was really important to bring in the patient voice. And so part of the definition comes from experts within the community to try to understand what different benchmarks mean for all of these definitions, but also what does it mean from a patient perspective? What does something like refractory mean to them? And one thing that we heard very loudly from the patient community is that refractory really shouldn’t be defined by a specific drug in a specific set of circumstances. What the patient certainly did not want is to say your refractory to a drug, and that sort of means that your disease has no hope for any future improvement down the road. It’s refractory to everything.
So patients really wanted to avoid that. So when we developed these definitions, we took that in mind to say, if you’re refractory to one specific drug, it means you don’t respond to that drug. You don’t have any clinically meaningful improvement, neither by a measure that we can assess in clinical practice or and from a patient’s own perspective. So patients don’t feel better and then there’s nothing we can measure to get better. So what that means is that particular drug under those circumstances is not effective, but that does not mean that somebody is necessarily refractory to other types of interventions that perhaps work with a different mechanism of action. That was very important to patients that I think makes a lot of sense from a clinical perspective
Alex Seluzhytsky:
In newly defined terms, even include simplified definitions for lay audiences in 10 words or less. For instance, refractory simplified definition is treatment doesn’t help or must be stopped. How do you think these definitions may affect the way neurologists think about and address refractory CIDP?
Dr. Jeffrey Allen:
Yeah, so the other thing that we really thought about when we developed these definitions that was we want them applicable to patients, clinicians, clinical trialists and other regulatory bodies. But we also know that if we make them so complicated and inaccessible that they’re not going to go anywhere. So we want the core definition to be there, but then also a definition that resonates with patients at all levels of the spectrum. And so this is where these more simplified definitions kind of come in that can kind of condense the core definition into something that’s really, really straightforward and that’s easy to remember and understand. So that’s where the refractory simplified definition comes in. And we have variations for this for all of the definitions that we’ve used. And so the value with them is just promoting the definition and widening the accessibility of the definition to as many people as possible.
Alex Seluzhytsky:
When we look at available data, nearly 30% of people living with CIDP do not respond to standard therapies, and 70% of those who do respond may have an incomplete response. Can you elaborate on the unmet need in the space and the need for alternative treatment options?
Dr. Jeffrey Allen:
Yeah, I mean even those numbers are certainly accurate from what we know, but using some of these definitions may be helpful to narrow those particular numbers down even more. But you’re absolutely correct, that at the end of the day, not everybody responds to the treatments that we have available. And even of those that do respond, there’s many people, 60, 70% or more that have some sort of partial response where they get better to a certain degree, but then don’t get better beyond that. The definitions will be helpful to really quantify those changes and also to measure how much residual deficits there are, potentially how much more improvement may be forthcoming if we do find therapies that work differently. Although just the nature of the disease makes it difficult for some deficits to come back no matter how aggressive we are.
Alex Seluzhytsky:
We’ve talked a lot about the importance of definitions and the importance of language, but the management of CIDP is not only about the words we use, it’s also about deepening our understanding of the biology behind the disease. Can you tell us what’s going on under the surface?
Dr. Jeffrey Allen:
Gosh, there’s a lot of exciting work that’s being done really to try to understand the immunobiological underpinnings of CIDP. And there’s some things we know and some things that we’re moving towards. So we know that it’s an inflammatory disorder. There’s probably an antibody mediated component of it. Inflammation is very important. There’s breakdowns of blood nerve barrier, which allows infiltration of things like antibodies and macrophage, which can damage the nerve. We’re also learning about the importance of the complement system in CIDP where complement when it’s activated in an inappropriate way leads to a cascading effect where the inflammation occurs, the nerve is attacked, and then the complement system targets the nerve for destruction with things like antibodies. And the complement system is a very complicated cascading pathway of enzymes, which ultimately lead to some terminal complement components that can accumulate in nerve, but stopping that complement cascade early in the pathway might prevent some of the inflammation in the signaling towards nerves that marks it for destruction.
Alex Seluzhytsky:
It’s great to see that a lot of research is going on right now in CIDP. So lastly, before we wrap up, can you please also speak to the importance of identifying biomarkers to track CIDP progression and care?
Dr. Jeffrey Allen:
Another huge unmet need in the field, and we thought about this a lot in the definition. So right now, the definitions of things like relapse and refractory and response are all based on patient perception and clinical outcomes of disability and impairment. There’s no biomarkers, which is a real unmet need because we really want to understand that if we’re making an impact, either we start a treatment and the treatment works or somebody’s off treatment, for example, and they worsen, is there really something that proves or tells us more convincingly that there’s really a change in nerve status and that may come in the form of a biomarker, preferably a blood-based biomarker that can be easily assessed.
So that’s really a major unmet need to the field, to find some sort of test that helps us to confirm disease activity with more and more certainty. There’s a couple of interesting candidates right now and a lot of really exciting research going into that area, but at least as we talk today, there’s no specific biomarker that we can rely upon in order to really say, you’ve got active disease, or your treatment is working, or you’ve had a relapse. It’s something that we really, really need.
Alex Seluzhytsky:
Definitely still a lot to do. Well, thank you a lot for joining us here today, and we appreciate all your efforts in advancing science and research in CIDP.
Dr. Jeffrey Allen:
Thank you.