This transcript has been edited for clarity.
Dear colleagues, I'm Christoph Diener from the University Duisburg-Essen in Germany. In this video, I will describe five recent studies.
Anti-Amyloid Drugs in Alzheimer's Disease
Let me start with the most exciting study, which is in mild Alzheimer's disease. We had a positive trial with an antibody against beta-amyloid at the beginning of this year, called lecanemab, which is now approved in the United States. There is a second monoclonal antibody, donanemab, which was also tested in beginning Alzheimer's disease. These patients were identified by the presence of amyloid or tau protein in PET measurements.
The TRAILBLAZER study randomized patients to donanemab or placebo. This was a double-blind, placebo-controlled study for 18 months in 1736 participants. In the active group, patients received the antibody every 4 weeks via the intravenous (IV) route. The primary endpoint was the Alzheimer Disease Rating Scale score, and the study had 24 additional secondary endpoints. The results were impressive. The study was not only positive for the primary endpoint, but for 23 of 24 secondary endpoints. The study also showed the already known adverse events from these monoclonal antibodies. On MRI, 24% of patients had edema or microbleeds.
In summary, this means that at present we have two monoclonal antibodies against beta-amyloid that showed efficacy in the early stages of Alzheimer's disease. In terms of everyday clinical practice, to set up the infrastructure for the diagnosis and treatment of these patients, and for follow-up, will be expensive and will be a major problem for most healthcare systems.
Let me move to an even earlier stage of the disease. The MIND trial investigated the Mediterranean diet combined with DASH, which is used in the treatment of hypertension, in older people and was published in The New England Journal of Medicine. The study randomized the 604 older patients to this special diet, which includes fruits and vegetables and avoids meat and cholesterol-containing foods. The control group received diet with caloric restrictions. These were older patients who had no cognitive impairment but had a family history of Alzheimer's disease and were obese.
The study went for 3 years, and unfortunately, there was no difference in cognitive function across 3 years between the two diets. The surprising result was that both groups showed an improvement in cognitive function across 3 years, which was probably due to the fact that including them in a study most probably led to better treatment of concomitant diseases. This means also that older patients at risk for Alzheimer's disease should have a healthy diet.
Spinal Cord Injury
Let me move to the spinal cord. One of the most serious diseases in neurology is paraplegia or tetraplegia due to spinal cord injury. At least from animal experiments, we know what the mechanisms are behind possible repair and degeneration in these conditions. We have biological factors and neurotransmitters that promote repair and axonal growth. Then we have biological factors that inhibit these repair mechanisms. Now there is a new molecule, soluble Nogo-Receptor-Fc decoy, which blocks the inhibitors of axonal growth and improves motor function after spinal lesions in animals.
For the first time, as described in Lancet Neurology, this drug was given to patients with cervical spinal cord injuries. The first group received the drug intrathecally as a proof of concept to show pharmacokinetics. In the second part of study, 24 patients were treated in a placebo-controlled design. Very importantly, this drug was well tolerated and the levels in the cerebrospinal fluid (CSF) were achieved that were needed to show a positive biological result. In a small study of patients, there was a signal toward efficacy, and now we need a larger phase 2 trial to see if this new approach is effective.
CBT and Opioids for Back Pain
Now let me move to back pain. There are many approaches to the treatment of chronic low back pain, and many of them, unfortunately, are futile. This is particularly true with treatment with drugs. The RESTORE trial in Australia randomized patients with chronic low back pain into three arms: cognitive-behavioral therapy in one group, cognitive-behavioral therapy in combination with movement sensor biofeedback, and the third group with usual care. In this study published in The Lancet, the primary endpoint was [self-reported activity limitation on the] Roland-Morris Disability Questionnaire at 13 weeks. There were 492 patients randomized. There was a clear, positive result for cognitive-behavioral therapy compared with standard of care. There was no additional benefit with movement sensor biofeedback. The downside is that it's very difficult to find behavioral psychologists who can teach patients with chronic low back pain the cognitive-behavioral therapy.
My last study is on opioids for the treatment of acute cervical or lumbar spine pain. This was the OPAL study, published in The Lancet. Unfortunately, many physicians still prescribe opioids for patients with acute pain in the cervical spine or lumbar. This placebo-controlled trial was done in Australia in 347 patients with acute back or neck pain existing for less than 12 weeks. Patients in the active treatment group received oxycodone in combination with naloxone up to a dose of 20 mg/d compared to placebo for 6 weeks.
There was no benefit of opioids. Opioids were not effective. Patients did better in the placebo group in terms of primary and secondary outcome. Therefore, with the exception of perhaps being a treatment for 2 or 3 days for extreme pain, there is no indication for opioids to treat acute pain, either low back pain or cervical pain. This is also important because the opioid crisis in the United States showed that putting people with back pain on opioids can promote dependency. This is something we definitely want to avoid.
Dear colleagues, I'm Christoph Diener, from the University of Duisburg-Essen. These were five very interesting studies published recently. Thank you much for listening and watching.
Medscape Neurology © 2023
Cite this: The Latest on Treatments for Alzheimer Disease, Spinal Cord Injury, and Back Pain - Medscape - Aug 17, 2023.