The most difficult part of living with a chronic illness is knowing that you’ll probably have to battle the symptoms for the rest of your life. Unless you reach remission or a cure is found in your lifetime, chronic illnesses tend to challenge you with some degree of discomfort every single day from the moment the first symptom manifests. For people who live with myasthenia gravis, this discomfort is often significant. 

The level of muscle weakness and fatigue experienced varies from person to person and it depends on how well the treatment is working. However, if MG is acting up and if all treatment options have been exhausted, it may be tempting to give in to despair. It feels like you can’t get anything done on your bad days and this loss of productivity can negatively impact your self-esteem. Not only that, but you can’t enjoy many of the things that used to make your life meaningful and exciting. Doctor’s appointments peppered all over your schedule, you still can’t figure out a way to make it better. 

We at FindMeCure know that sometimes available treatments fail and most patients are not informed about alternative options. Many doctors themselves can’t keep up with clinical research and don’t think to refer you to a relevant clinical trial. If you’ve exhausted existing treatments with no success so far, clinical trials could help you find something that works. 

Immune system suppression is still a course of action

A phase III trial in China is testing azathioprine against leflunomide when both are combined with corticosteroids. Patients with different clinical types of myasthenia are eligible for the study as it aims to evaluate the acute and long term toxicity of the treatments. Azathioprine is an immunosuppressant used for Crohn’s and ulcerative colitis as well as in cases of a kidney transplant and it can have some serious side effects in rare cases – for example, if you have a genetic deficiency of the thiopurine S-methyltransferase enzyme – bone marrow suppression can occur. Most commonly, however, the side effects include diarrhoea, rash, fever, muscle aches, dizziness. The WHO lists it as one of the safest and most effective on their List of Essential Medicines

Leflunomide is also an immunosuppressant used for the treatment of other autoimmune diseases like rheumatoid arthritis. It’s also known as a DMARD (disease-modifying antirheumatic drug) – DMARDs are highly effective but come with the risk of liver damage or lung infections. All of the risks we listed result from suppressing the immune system – so far one of the most effective methods in the treatment of autoimmune diseases. 

How does azathioprine compare to other immunosuppressants? This observational trial with 2 locations in the USA is trying to answer the question in order to help Mg patients and their treatment teams to choose the best option. The drug AZT is compared against is Mycophenolate Mofetil – another drug used to prevent organ rejection in patients who received a transplant. Unlike other drugs of its class, it usually doesn’t cause toxicity of the kidneys and fibrosis and it has been modified to prevent gastrointestinal issues when administered to patients with autoimmune disease. 

MuSK-MG patients will have more options

MG treatment is especially disheartening for MuSK-MG patients who typically don’t benefit from most available treatments, including immunosuppressants. A phase III clinical trial in the US is evaluating the long-term safety and effectiveness of amifampridine phosphate – an orphan drug (a drug used for diseases so rare, it’s not profitable to produce it, so the company needs governmental assistance) so far used for the treatment of Lambert-Eaton myasthenic syndrome (LEMS).   

FcRn antagonists could be the answer 

A recruiting clinical trial in phase III is looking for patients in Belgium. The study is investigating the effects of rozanolixizumab compared to a placebo in generalised Myasthenia gravis before the treatment is released on the market. Rozanolixizumab binds to human neonatal Fc receptor (FcRn) – a receptor that inhibits the degradation of pathogenic IgG autoantibodies (the autoantibodies that mistakenly attack the body’s own tissues). The expectation is that by reducing the levels of these antibodies, rozanolixizumab will alleviate MG symptoms. So far results from previous clinical trials show that the drug is well tolerated and administering it under-the-skin is better than injecting it into the bloodstream. 

M281 doesn’t mean much to anyone who isn’t involved in pharma or clinical research for autoimmune diseases, so when this phase II trial states as its purpose “to evaluate the safety, tolerability, and efficacy of M281” – what are we to understand? The other name of M281 is nipocalimab – a drug that, like rozanolixizumab blocks the FcRn-mediated recycling of IgG. The trial is being conducted at a few locations in Italy and Poland. 

Another phase II clinical trial in the US and Canada is comparing RVT-1401 against placebo. What is RVT-1401? Yet another agent that blocks the Fc receptor (FcRn) in order to prevent it from prolonging the half-life of IgG molecules (remember that those are the bad guys, autoantibodies that wreak havoc), RVT-1401 is particularly appealing alongside other drugs of its class because it doesn’t result in widespread immune suppression. FcRn inhibition has a similar effect to TPE (therapeutic plasma exchange) but it selectively reduces the IgG autoantibodies without many of the limitations of TPE. 

This method of treatment is being explored for its potential both as maintenance therapy and as a way to handle myasthenic crises. In a mouse model, FcRn inhibitors demonstrated therapeutic potential in MuSK-MG as well, although it’s still early to draw conclusions. These agents, however, could also prove beneficial in other autoimmune diseases like chronic inflammatory demyelinating polyneuropathy and idiopathic thrombocytopenic purpura. 

A recruiting phase III trial with 4 locations in Europe is testing ARGX-113 (another FcRn inhibitor) against placebo. The good news is that even if you can’t join the trial, phase III is the last step before a new treatment hits the market which means there’s a good chance that MG patients outside the trial will soon have access to this innovative method. 

If you want to contribute to medical knowledge about your condition

If your treatment works for you and you’re not looking to find a better option, you can still help the scientific community gain more information about myasthenia gravis. There’s a number of observational trials you can join like this one which aims to “collect the clinical data of myasthenia gravis (MG) patients, assess outcomes and adverse effects of different treatment regimens, and search for risk factors of conversion to generalized MG”. Alternatively, you might want to join a trial evaluating the effects of MG-related physical inactivity on overall health. By volunteering your time to medical research you’re contributing to the growing data health professionals have at their disposal. In turn, this leads to better treatments and expanding healthcare options.

If you want to join a clinical trial, you can search for your preferred therapeutic method. You can choose to enrol in an observational study or receive treatment but in both cases, your participation helps to advance medical science.

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