Free biotech stocks directory, pharma stocks, telemedicine stocks ...
Efgartigimod Offers Hope In Chronic Inflammatory Demyelinating Polyneuropathy
PHOENIX -- A subcutaneous infusion of efgartigimod cut the risk of relapse in patients with a rare but serious immune-mediated neuropathy, according to the phase II ADHERE trial.
Patients with diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP) treated with efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) saw a 61% reduction in the risk of relapse versus placebo, based on time to the first adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) deterioration of ≥1 point (HR 0.39, P=0.000039), reported Richard Lewis, MD, of Cedars-Sinai Medical Center in Los Angeles.
Patients on the study agent also experienced longer time to relapse versus those on placebo, Lewis and colleagues stated in a poster at the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. The rapid separation of the Kaplan-Meier curves began at week 4 and was sustained through week 48.
All ADHERE patients were treated in clinics where they received the 90-second infusion of efgartigimod coformulated with recombinant human hyaluronidase PH20 (rHuPH20) which allows for rapid subcutaneous administration of larger volumes, Lewis said. IV efgartigimod (Vyvgart) was approved by the FDA in 2021 as a treatment for generalized myasthenia gravis (gMG) and the subcutaneous formulation was approved in 2023 for gMG.
Lewis told MedPage Today that ADHERE "did not have an at-home component to it...But I think in the future there may very well be a way that patients can self-administer PH20."
Arindra Jayasekara, MD, of Riverside Community Hospital/University of California Riverside, told MedPage Today said the ADHERE results will broaden the treatment field for people with this rare and serious autoimmune disease of the peripheral nervous system. "Right now, these patients have limited options such as IV immunoglobulin or plasma exchange...I think that eventually the subcutaneous infusion will be something that can be done at home."
But Jayasekara, who was not involved in the study, cautioned that "patients have to be educated about the risks and benefits. It will be helpful for those individuals who may not have the wherewithal to go to an infusion center. Subcutaneous infusion would be a better choice for these people or others who have problems with IV infusions."
ADHERE had two stages: Stage A enrolled 322 patients with CIDP who underwent treatment. Responders in stage A were entered into Stage B, where the primary endpoint was the relative risk of relapse based on time to relapse on the INCAT Disability Score, which ranges from 0-10 for arm and leg disabilities.
Patients in both stages were about age 54 and over a third were female. The average time since diagnosis with CIDP was around 4 years. The adjusted INCAT scores for those in stage A, stage B, and placebo were 4.6, 3.1, and 3.3, respectively. Grip strength scores in the dominant hand were 38.5 kPa, 54.9 kPa, and 58 kPa, respectively. More than 60% had unstable, active CIDP.
In stage A, patients on the study agent demonstrated a clinically meaningful mean improvement of 7.7 points on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) of upper and lower limb disability, along with a 12.3 kPa improvement in grip strength. This clinically meaningful benefit was maintained in stage B by patients on the study agent but was lost in those on placebo.
In stage B, those on the study drug had a lower relapse rate versus placebo at week 24 (26% vs 54%) and week 48 (34% vs 60%).
The most frequent treatment-related adverse event (TRAE) was injection site reactions (20% of stage A patients; 10% of stage B patients), but all cases were mild to moderate and resolved over time. Lewis stated that about 5% of patients in both groups reported a serious AE, but none were TRAEs. There were two deaths in stage A (n=1 COVID-19; n=1 worsening CIDP). There was a single pneumonia-related death of a placebo patient in stage B.
Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.
Disclosures
The trial was funded by argenx.
Lewis disclosed relationships with CSL Behring, Grifols, Pfizer, Sanofi, argenx, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, and Momenta.
Jayasekara disclosed no relationships with industry.
Primary Source
American Association of Neuromuscular & Electrodiagnostic Medicine
Source Reference: Lewis R, et al "Efficacy, safety and tolerability of subcutaneous efgartigimod PH20 in patients with chronic inflammatory demyelinating polyneuropathy: Results from the ADHERE trial" AANEM 2023.
Please enable JavaScript to view the comments
Vitamin D May Help Reduce Peripheral Neuropathy Caused By Chemotherapy
A new study has found evidence that vitamin D supplements may reduce chemotherapy-induced neuropathy (CIPN) in people with low levels of the vitamin.
Peripheral neuropathy is often described as numbness, tingling, or burning sensation in the hands and feet that can dramatically interfere with a person's ability to perform normal activities of daily living including bathing, dressing, and cooking, according to the senior researcher Daniel L. Hertz, PharmD, PhD, an associate professor at the University of Michigan College of Pharmacy in Ann Arbor.
The findings, published in the November 2023 issue of JNCCN — Journal of the National Comprehensive Cancer Network, suggest that this inexpensive and easy-to-access solution could improve long-term quality of life for people with cancer and potentially lessen racial disparities, according to the authors.
Chemo Drug Paclitaxel Treats a Variety of CancersIt's estimated that as many as 6 in 10 people treated with the cancer chemotherapy drug paclitaxel develop peripheral neuropathy, and as many as 3 in 10 have severe symptoms, according to a study published in the February 2019 BMC Cancer.
Paclitaxel is used to treat advanced cancer of the ovaries and breasts, non-small-cell lung cancer, and Kaposi sarcoma (a cancer of the skin and mucous membranes that is commonly found in people with AIDS), according to Mayo Clinic.
The drug interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected, other unwanted side effects occur, sometimes right away, but others may not develop until months or years after the medicine is used.
Peripheral Neuropathy From Chemo Is More Likely to Occur in People Who Are Vitamin D DeficientThe lingering numbness, tingling, or burning can be largely untreatable and sometimes permanent, making it critical that people receiving chemotherapy and their care teams monitor for and address the development of treatment-related peripheral neuropathy — before symptoms become intolerable, according to the authors. "The condition can irreversibly reduce their physical, social, emotional, and financial quality of life," says Dr. Hertz.
To look at how vitamin D levels might impact the likelihood of peripheral neuropathy in people undergoing chemotherapy, investigators used data on about 1,200 patients with early-stage breast cancer from the SWOG S0221 study, which compared chemotherapy regimens in high-risk early stage breast cancer.
They found that 20.7 percent of patients with vitamin D deficiency experienced at least a grade 3 level of chemotherapy-induced peripheral neuropathy (CIPN), compared with 14.2 percent of those with adequate vitamin D levels.
In an accompanying study, researchers strengthened this connection by inducing vitamin D deficiency in mice, which caused symptoms suggesting brain toxicity.
These findings reveal a significant association between vitamin D insufficiency and an increased incidence of chemotherapy induced peripheral neuropathy, said Mei Wei, MD, an oncologist who specializes in treating breast cancer at the Huntsman Cancer Institute at the University of Utah, in a press release. "This study finding uncovers a new potential strategy to combat CIPN, thereby improving the quality of life for cancer patients undergoing treatment. It is an exciting step forward in our continuous mission of patient-centered cancer care," said Dr. Wei, who was not involved in this research.
Findings Could Be Used to Help Reduce Health Disparities in CIPNIt's well established that Black individuals have much higher risk of vitamin D deficiency, says Hertz. "We are excited by the possibility of this research providing an explanation for the known racial disparity: Black patients have about double the risk of reporting CIPN," he says.
Vitamin D supplements could potentially provide a simple, cheap, and safe strategy to reduce chemotherapy-induced peripheral neuropathy and reduce this disparity, says Hertz.
Should People Who Undergo Paclitaxel Chemotherapy Treatment Take Vitamin D Supplements?Patients can easily take over-the-counter vitamin D supplements to increase levels without much risk of negative consequences, says Hertz.
But should everyone who undergoes this type of cancer treatment start taking vitamin D?
If testing indicates you're vitamin D deficient, you should receive supplementation for several reasons, regardless of whether it prevents CIPN, says Hertz. Before starting on the supplements, talk to your provider about the recommended dose — too much vitamin D can be harmful, according to MedlinePlus.
It is likely too early to recommend vitamin D assessment prior to treatment in all patients, since it hasn't been demonstrated that vitamin D supplementation prevents CIPN, says Hertz. "Further research is needed to prospectively demonstrate that vitamin D supplementation in vitamin D deficient patients prevents peripheral neuropathy," he says.
Peripheral Neuropathy And HIV
Key pointsPeripheral neuropathy is a common condition amongst people living with HIV.
Neuropathy is damage to the nerves. Nerves transmit signals within the brain and spinal cord (the central nervous system or CNS), and extend from the CNS to the muscles, skin, and organs.
The nerves that are outside the CNS are called the peripheral nervous system (PNS). They transmit sensations (such as touch, vibration, and pain) and control movement. They are also important for balance.
Some of the peripheral nerves control body functions over which we have no conscious control, such as blood flow to the organs or the movement of food through the intestines. This is called the autonomic nervous system.
SymptomsPeripheral neuropathy usually involves damage to the nerves in the feet or, less commonly, the hands, arms, and legs. When nerves are damaged, their signals do not work properly and can misfire. This results in symptoms that can range from mild tingling and numbness through to pain that makes it impossible even to wear a pair of socks. Some people lose strength in their hands, making it difficult to grip anything. Symptoms are usually 'symmetrical', in other words, felt equally on both sides of the body.
Peripheral neuropathy commonly affects the longest nerves in our bodies first, which is why it is usually experienced in the extremities, such as the feet or hands. Occasionally the autonomic nervous system can also be affected, causing symptoms such as dizziness, diarrhoea and erectile dysfunction (inability to get or sustain an erection).
People's experiences of neuropathy will differ in terms of intensity and how much it affects their life. This is because pain is experienced differently by each person and influenced by a range of biological, psychological, and social factors. These include factors such as genetics, stress, and temperature. There's more information about dealing with pain on another page.
As there are several possible causes of nerve damage, it is very important to tell your doctor if you have any tingling, numbness, or pain in your hands or feet so that the cause can be properly investigated.
Causes of peripheral neuropathyThe different causes of peripheral neuropathy in people living with HIV, and how they cause nerve damage, are not yet fully understood. The risk of neuropathy in people living with HIV appears to increase if they are older, taller, obese, or have had HIV for a long time.
Neuropathy may be caused by inflammation related to HIV itself, some older antiretroviral drugs, or a combination of both. HIV-related neuropathy tends to emerge gradually whereas antiretroviral-related neuropathy usually develops more quickly and can usually be stopped from worsening by changing medication. The risk of HIV-related neuropathy is reduced by prompt diagnosis and treatment of HIV, before the immune system is too damaged (indicated by a low CD4 count).
The antiretroviral drugs most associated with neuropathy are older treatments that were used in the past – in particular, didanosine (ddI, Videx), zalcitabine (ddC, Hivid), and stavudine (d4T, Zerit). The use of these anti-HIV drugs is now avoided as much as possible.
Not all causes of peripheral neuropathy are necessarily linked to having HIV. For example, uncontrolled diabetes is a leading cause of peripheral neuropathy. There are many other health conditions which can also cause peripheral neuropathy, which means that diagnosing the underlying cause can require many different tests.
Neuropathy can also be caused by treatments for other health conditions including some antibiotics and medications used to treat cardiovascular disease, tuberculosis, and cancer. For example, peripheral neuropathy is a common side effect of vinblastine and vincristine, which are chemotherapy drugs used to treat many types of cancer including Kaposi's Sarcoma and lymphomas.
If you take more than one of these drugs, the risk of developing neuropathy may be increased. If you have previously had neuropathy caused by something else, you may also be more likely to develop neuropathy from taking one or more of these drugs.
Glossary peripheral neuropathyDamage to the nerves of the hands and/or feet, causing symptoms ranging from numbness to excruciating pain.
symptomAny perceptible, subjective change in the body or its functions that signals the presence of a disease or condition, as reported by the patient.
central nervous system (CNS)The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.
antiretroviral (ARV)A substance that acts against retroviruses such as HIV. There are several classes of antiretrovirals, which are defined by what step of viral replication they target: nucleoside reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; integrase (strand transfer) inhibitors.
Peripheral neuropathy can be caused by consuming large amounts of alcohol over many years: the best treatment in this case is to stop or significantly reduce your intake of alcohol.
Peripheral neuropathy can also be caused by a shortage of vitamin B12, which can be more likely among people living with HIV who have low CD4 counts. Vegans are also at greater risk because vitamin B12 is only present in meat and dairy products. If medical tests confirm that you have a vitamin B12 deficiency, your doctor may offer supplements of vitamin B by injection (tablets are largely ineffective because vitamin B is poorly absorbed in the gut). Increasing the vitamin B12 content of your diet may also help a little; foods that are rich in the vitamin include fish, kidneys, liver, beef, pork, eggs, and dairy products. Some vegan foods are fortified with vitamin B12 including certain cereals, nutritional yeast, and non-dairy milks. Ask to see a dietitian at your clinic for more advice.
DiagnosisIf you suspect you may have peripheral neuropathy, speak to your GP or HIV doctor so your symptoms can be assessed. This will involve taking a medical history and some basic tests of co-ordination, reflexes, and memory.
They may refer you to a specialist doctor to conduct this assessment or to have further tests. For example, a nerve conduction study tests the electrical function of your nerves and can identify damage in the large fibres of a peripheral nerve. This is done by placing electrodes on your skin which stimulate the nerve and record its response. It may feel a little uncomfortable, but it isn't usually painful.
In some cases, a more specialised test may be needed to look for damage to smaller nerve fibres. Quantitative Sensory Testing assesses your ability to feel different sensations (such as touch, cold, warmth, or vibration). Sometimes a small piece of skin (about 4mm square) may be taken from your calf under local anaesthetic so the number of nerve fibres in the outer part of your skin (the epidermis) can be counted.
Treatment and managementIf you are diagnosed with peripheral neuropathy, your doctor will then attempt to identify the underlying cause. This will usually require a number of blood tests. Treating the underlying cause is the usual approach to managing peripheral neuropathy, but not all underlying causes are treatable.
If you suspect you may have antiretroviral-related neuropathy, speak to your doctor who may recommend stopping or switching treatment or reducing the dose. If you stop or switch your treatment, you may later be able to go back onto a reduced dose of the drugs without the neuropathy returning.
For some people, symptoms of peripheral neuropathy may disappear once the underlying cause is treated. For others, however, the pain may become episodic (flaring up occasionally) or persistent (chronic or long-lasting). It may relate to changes in temperature – very cold weather, for example. The aim of treatment is to help you manage your pain so that you can reduce the symptoms and improve your quality of life.
Speaking to medical practitioners who understand neuropathy and pain science can be very helpful as they can help you to understand the various influences on your pain, including biological, psychological, and social factors, and help you to manage these better. Your GP or clinician may be able to refer you to a pain specialist. You can also read more about the causes of persistent pain and how it can be managed on our pain page.
Living with peripheral neuropathy can have a substantial impact on your life, and you may feel isolated and depressed. Seeking support is vital to offsetting these feelings and helping you to manage your symptoms. You can join online forums or attend peer support groups where there may be people who are also living with HIV-related neuropathy. You should also explain to your family and friends what you are going through and how they can offer support.
Different people find different things helpful in managing pain:
Patches and creams containing capsaicin. Capsaicin is a substance made from chilli peppers and is used in many topical painkillers. Its pain-stimulating effect appears to temporarily overwhelm the signals that cause chronic pain. Treatment with strong (8%) capsaicin patches can partially relieve symptoms of peripheral neuropathy for several months and can be repeated at regular intervals.
Heat and cold. Temperature can influence your experience of pain and numbness. You may find that soaking your feet in cold water and wearing warm socks in bed can help to reduce pain.
Avoiding tight shoes and socks.
Pain self-management programmes can help improve your quality of life by giving you an active role in managing your pain. They use evidence-based psychological approaches such as acceptance and commitment therapy to support people living with persistent pain to feel more in control of their lives and better able to cope with pain. Ask your doctor for a referral to a specialist pain management service if you think you would benefit from such a programme.
Gentle exercise. If you are experiencing muscle weakness, exercise can help to build your muscle strength. Any exercise is better than none, so its fine to start slowly, set yourself simple goals, and build up your activity gradually.
Your doctor can give you advice on the type and amount of activity that is safe for you. They may refer you to a physiotherapist who can help you with some exercises if you are worried about exercising on your own.
It's best if you find an exercise you enjoy, and you might find that you are more motivated and enjoy it more in a group.
Medications. Some medications have been found to relieve pain associated with peripheral neuropathy. It is not certain how they work but it is probably by altering the chemicals in your nerves and brain which affect how you feel pain. These drugs include amitriptyline, gabapentin, pregabalin or duloxetine. These drugs can be used to treat depression or epilepsy, but they can also be prescribed specifically for pain relief.
Unlike conventional painkillers, these medications will need to be taken regularly over extended periods to achieve their effect. It is important to recognise that they will not cure the neuropathy and are only prescribed for symptom control. They will never take away 100% of your pain and may have side effects. Your doctor will work with you to find the medication and dose which best suits you and doesn't give you too many side effects.
Cannabis or morphine-like drugs (opioids) are not recommended for treating neuropathic pain. They can cause serious side effects.
Complementary therapies. Many people find acupuncture, yoga, mindfulness, and breathing exercises help to reduce pain and manage their symptoms.
Further informationThe Foundation for Peripheral Neuropathy website has further information, including tips for managing peripheral neuropathy.
The Physiotherapy Pain Association has a number of useful resources for people living with pain, including general information about pain and tips for keeping active.
The Footsteps Festival provides a series of online events co-produced by people with pain to explore creative ways of living well with pain.
Comments
Post a Comment