Hand-Me-Downs: The CIDP Therapeutic Landscape

September 4, 2018

The director of the electromyography laboratory and a professor of neurology at Cedars-Sinai spoke about the treatment options for CIDP.

Richard A. Lewis, MD

For physicians that treat chronic inflammatory demyelinating polyneuropathy (CIDP), getting effective therapies for their patients often involves waiting for other conditions to develop them.

Richard A. Lewis, MD, the director of the electromyography laboratory and a professor of neurology at Cedars-Sinai, has been given these hand-me-down treatments for patients for quite some time. While these therapies have brought clinicians to a point where they can control CIDP, the goal of getting patients into remission is still a long shot for the majority.

To provide a more in-depth look into the landscape of CIDP treatments, Lewis spoke with NeurologyLive about the available options, what has been explored, and what treatments the disease really needs.

NeurologyLive: What’s the therapeutic landscape of CIDP look like for you?

Richard Lewis, MD: We currently have a number of treatments for CIDP that control the disease. The first-line treatments of intravenous immunoglobulin (IVIG) and corticosteroids have been shown to be effective in a majority of patients. The corticosteroid approach has changed a little bit, in that more people are using pulse high dose steroids once a week, or sometimes once a month, rather than the daily corticosteroids, and there are some issues of both safety and efficacy that favor the pulse approach.

Saying that, what we know about CIDP is that about one-third of patients at the most will be able to go into remission, and only about 11% in our studies on disease activity seem to go into a long-term remission of 5 years or more—what might have been considered a cancer cure. It’s a very small percentage of patients who are able to go into remission. There are other treatments besides the primary ones—IVIG and corticosteroids—mostly those medicines are medicines used for transplants, like cyclosporine, or tacrolimus, or mycophenolate, or azathioprine (Imuran), but each of those have their own risks and adverse effects and it’s not clear that they get people into more remission or more “cure.” There are other approaches to give immunoglobulin. Subcutaneous immunoglobulin, SCIG, has recently shown to be effective and can be a nice substitute to IVIG, but those treatments require persistent use, indefinitely, sometimes for the rest of their life.

The need is to find the treatment that is relatively safe that can put people into remission, or cured, and we’re not there yet. There are some chemotherapy type medicines like cyclophosphamide that probably get more people in remission than the other drugs, but there’s not a ton of data to support that contention—although the experience of many of us is that it does do that. The problem is it carries more risks, so do you continue with a long-term treatment like IVIG or some element of steroid forever? Is that safer or better than getting a short course of cyclophosphamide that may keep you in remission for years? It’s a tough question, and each patient and their doctor need to have that discussion.

Are there any developments in play that could be opportunities to improve that landscape?

The opportunity is to find treatments that will put people in remission better. People have been looking at B-cell depletion, people have been looking at compliment inhibitors. Probably, the complement inhibitors are not going to put people in remission. It may just be an added benefit to making people better. And there are still patients out there with CIDP who don’t respond to the first- or even second-line treatments. The disease is can be debilitating. It can put people in wheelchairs, and sometimes worse, but most of the time the disease is not shortening lives in a major fashion. There are some patients who die of the disease but pretty rare.

Is there anything in that pipeline that’s striking, or could represent a shift in improving care?

What’s been exciting in the last 3 to 4 years has been the discovery of antibodies directed against certain targets that, in a small percentage of patients with CIDP, seem to be the cause of the disease. Before, we didn’t really know what caused CIDP, and although we knew antibodies had to play a role or thought they had played a role, we could never define that. But, at least in this small population—5% or so of CIDP—antibodies to neurofascin-155 and contactin-1, and now some other elements of the apparatus node of Ranvier in the paranodal region have been found. That’s an exciting aspect because those disorders actually have a very strong treatment. B-cell depletion seems to be a very strong treatment in those disorders. Clearly, our ability to treat the majority of patients with CIDP will be dependent on finding the more specific mechanism of why their disease has occurred and then we can target those. That’s been encouraging.

The possibility of b-cell depletion—ocrelizumab that’s now being used in multiple sclerosis—there have been a number of encouraging small series suggesting that, in some patients, it seems to be highly effective and put people in remission for a reasonable period of time. But that trial hasn’t started and there’s been an exploration of having a trial for b-cell depletion, but we’re a good year away from having that organized, probably more like 2 years. But we have some commitment to do that, so that’s exciting.

CIDP, being such a rare a disease, frequently has to look at other disorders that are more common to come up with possible treatments for our disease. Transplant immunology, rheumatoid arthritis immunology, multiple sclerosis, all those disorders. As things develop in those diseases, those of us interested in CIDP, and Guillain-Barre, and other immune-mediated neuropathies, consider those as potential useful agents in our disease. We tend to be not the first disorder to be tried for a variety of reasons—a small number of patients, it’s not necessarily the best market for pharmaceutical companies in terms of how much money that they’re going to invest versus their return. But we end up having those potential explorations. They do occur, it just takes a little bit of time.

Transcript edited for clarity.