Article In Brief
With the approval of a new drug for myasthenia gravis in December, neuromuscular specialists say they now have a host of new options for managing symptoms of the disorder. Four myasthenia gravis experts assess the current options and discuss their criteria for choosing one therapy over another.
Patients with myasthenia gravis (MG) will have another treatment option now that the US Food and Drug Administration approved a new targeted therapy in December, efgartigimod. The drug, which will sell under the brand name Vyvgart, is intended for adults with generalized myasthenia gravis who are positive for the anti-acetylcholine receptor (AChR) antibody.
Neurologists say the novel drug is likely to enhance the already growing ability to treat MG, a rare autoimmune disorder of the postsynaptic neuromuscular junction commonly characterized by a depletion of AChR. The Myasthenia Gravis Foundation estimates that 36,000 to 60,000 people in the US have MG, though the number could be higher because the disease is thought to be underdiagnosed.
I have really never felt so optimistic in terms of speaking with patients about their different options, Amanda C. Guidon, MD, MPH, assistant professor of neurology at Harvard Medical School. We have more therapies and there is this rich pipeline for drug development that will target therapies at (MG) pathophysiology.
Dr. Guidon, who directs the MGH Myasthenia Gravis Clinic at Massachusetts General Hospital, said MG mortality has decreased from 40 percent to 5 percent, though.
Still, she said, there is still a long way to go in terms of reducing MG symptoms, as well as achieving a understanding which therapies, from thymectomy to plasma exchange to oral and infused medications, are best suited for which patients.
MG typically is marked by fluctuating weakness in muscles controlling the arms, legs, face, mouth and throat. It can present as generalized or ocular disease.
Efgartigimod is the first in a new class of medication, according to the approval announcement by the FDA. The drug, which is infused, is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the circulation. The drug reduces overall levels of IgG, including the abnormal AChR antibodies.
We are in a new phase of revolution in how we manage patients, said James Howard, MD, professor in the department of neurology at the University of North Carolina, who led clinical trials of efgartigimod. With additional targeted drugs for MG under development, the treatment landscape over the next five to 10 years will radically change.
Dr. Howard was the principal investigator for the phase 3 ADAPT trial that served as a basis for the FDA approval of efgartigimod. The 26-week multicenter, international study randomized 167 MG patients to efgartigimod or placebo. By measure of the Myasthenia Gravis Activities of Daily Living (MG-ADL), the study, reported in Lancet Neurology in July 2021, found that 68 percent of patients with AChR antibodies responded to treatment during the first cycle of efgartigimod, compared with 30 percent of the placebo group. More patients receiving the active drug also demonstrated response on a measure of muscle weaknessthe Quantified Myasthenia Gravis Score (QMG)compared with placebo, according to the FDA. The most common side effects experienced by participants on efgartigimod were respiratory tract infections, headache, and urinary tract infections.
Dr. Howard said the drug is continuing to be evaluated in an open-label study, and is also being formulated for subcutaneous injection, and that approach is also being studied.
Dr. Howard said that until recently the goal of MG therapy has been mostly to reduce the burden of symptoms, which include weakness in the arms and legs, trouble swallowing, impaired speech, eyelid dropping and double or blurred vision. He said the focus is now shifting to include reducing treatment burden, which he said is problematic for many MG patients. He said that registry data on patients in different countries around the world show that a significant number of patients report being unemployed and having to miss work, or they meet other measures indicative of a low quality of life.
Another study of more than 1,000 MG patients from Sweden, for example, found that 47 percent of patients reported symptoms that measured 3 or more on the MG-ADL score, signaling they are not satisfied with their current disease state. An editorial that accompanied the study in Neurology in October 2021 was titled People with Myasthenia Are Getting Better, but Are They Doing Well?
While neurologists have been able to reduce mortality from MG by generally improving muscle strength, we now know that up to half of patients with MG continue to live without the adequate vigor and stamina to properly enjoy life, the editorial said.
Much of the current thinking on how to treat MG is contained in a 2020 document, International Consensus Guidance for Management of Myasthenia Gravis, which was written by an international panel of 15 experts convened by the Myasthenia Gravis Foundation.
The document, which updates one from 2016, noted that evidence-based recommendations for the treatment of myasthenia gravis have historically been difficult to develop because of limited evidence from studies with a low risk of bias such as large, well-designed randomized controlled trial studies.
The document, which predates the approval of efgartigimod, updated previous recommendations for thymectomy and also included new recommendations for the use of rituximab, eculizumab and methotrexate.
Vera Bril, MD, professor of neurology at the University of Toronto, said any treatment plan for MG has to begin with an accurate diagnosis.
One of the first steps is to decide if they have a thymoma or not because if there is, the patient may need surgery, she said. In general, thymectomy is done in patients who are AChR antibody positive and under the age of 50. Dr. Bril said research has shown that older patients do not show benefits and they are more prone to surgical complications than younger patients.
The consensus guideline recommends that for patients without thymoma who have generalized disease and are antibody positive, thymectomy should be considered early in the disease to improve clinical outcomes and to minimize immunotherapy requirements and the need for hospitalization for disease exacerbations.
Dr. Bril said that in spite of newer therapies, we still use a lot of prednisone in our patients because it is extremely effective for this disease, despite potential side effects such as weight gain, osteoporosis, and diabetes. She said options such as azathioprine and mycophenolate take a minimum of 12 months to tell if they are working. If you are waiting that long for these drugs to take effect, it takes a long time out of a patient's life.
Dr. Bril, who was an investigator for the clinical testing of efgartigimod, said the drug could one day replace the use of rapid, short-acting intravenous immunoglobulin therapy for MG. While the drug was primarily tested in patients with positive AChR antibody status, she said there is some evidence to suggest it could help those with a negative antibody status.
Gil Wolfe, MD, the Irvin and Rosemary Smith Professor and Chairman of Neurology at University at Buffalo. SUNY, and coauthor of the 2020 consensus guidance, said he sees several treatment trends emerging for MG.
The approach of many of us has changed in the last few years, whereby we try to be more aggressive with treatment earlier based on data suggesting that being aggressive at the time of disease diagnosis pays off dividends over time in terms of more favorable patient outcomes, he said.
He said there also is growing data that patients who reach certain favorable milestones earlier, such as within the first year or two after diagnosis, tend to have a more stable course long term, perhaps for decades, he said.
He predicts that another treatment approach that will become more common is the use of the newer drugs, such as eculizumab and efgartigimod, as bridge therapies.
These newer agents that work relatively quickly will be used to bridge patients while we await conventional oral therapies such as corticosteroids and the so-called steroid-sparing immunosuppressants, to take hold, he said.
He said a treatment plan that still does rely on less expensive conventional agents that have been used for several decades in MG could spare patients from some of the unique risks posed by newer therapies such as the complement inhibitors in regard to infection from encapsulated bacteria; lower overall treatment costs to the healthcare delivery system since conventional oral agents are far less expensive; and also relieve some of the provider and patient burden that is inherent for new agents that require intravenous or subcutaneous delivery.
Dr. Guidon said that as treatment options for MG continue to expand, it is going to become easier and easier to escalate treatment and we want to make sure the diagnosis is correct. She said that patients may be experiencing some symptoms not necessarily caused by MG, and it is important to establish what's in the myasthenia bucket and what is outside of it.
Dr. Guidon said understanding where a patient is in terms of disease severity and other comorbidities is also key to treatment planning. She said there also may be cost and access issues to consider because a patient's insurance may not cover a given treatment, which may reach into the hundreds of thousands of dollars.
Deciding on treatment for MG is really a collaborative effort and evolves over time, she said.
Dr. Bril has received honoraria for consulting with UCB, Momenta, Janssen, Roche, Octapharma, Grifols, Alnylam, Akcea, CSL, Ionis, Immunovant, Sanofi, Takeda, Alexion. Dr. Wolfe has been a consultant for Grifols, Alexion, ArgenX, Takeda, BPL, and UCB; has served on the speaker's bureau for Grifols and Alexion; and has received grant/research support from ArgenX, Ra/UCB, Immunovant, Roche, Alexion, Sanofi, NINDS/NIH, and the Myasthenia Gravis Foundation of America. Dr. Howard has received honoraria for serving on the advisory board of Alexion Pharmaceutics, argenx BVBA, Ra Pharmaceuticals (now UCB), Immunovant, Regeneron Pharmaceuticals, Sanofi, USA, Toleranzia AB, and Viela Bio Inc. (now Horizon Therapeutics). He has research support paid to his institution from Alexion Pharmaceuticals, argenx BVBA, The Centers for Disease Control and Prevention, Millenium Pharmaceuticals, NIH, PCORI, and Ra Pharmaceuticals (now UCB).
Here is the original post:
Expanding Treatment Options for Myasthenia Gravis: Why... : Neurology Today - LWW Journals
- Dr. Machida of Second to Creation Awarded Castle Connolly Top Doctor - Digital Journal - May 15th, 2022
- Why Male Clients of This Luxury London Skin Care Clinic Just Love Anti-Wrinkle Treatment - Digital Journal - May 15th, 2022
- More than meets the eye - The New Indian Express - May 1st, 2022
- Is gout reversible? Treatment, management, and more - Medical News Today - May 1st, 2022
- "He sold me a fairytale to fill his own pockets": The horror reality of botched breast implants. - Mamamia - April 18th, 2022
- The Evolution of Looks and Expectations of Asian Eyelid ... - January 21st, 2022
- Eyelid Spasms (Eye Twitching or Eye Twitch) | Kellogg Eye ... - January 21st, 2022
- Squints is saved, with help from Animal Shelter Foundation - Tallahassee.com - November 25th, 2021
- The Best Tear Trough and Under-Eye Filler | Dr. Brett ... - November 10th, 2021
- Monolid Eyes: Why They Are Beautiful and More - November 10th, 2021
- Home Page: Journal of Oral and Maxillofacial Surgery - November 10th, 2021
- Dr. Luis Macias and Aesthetic MdR Named Top Plastic Surgeon, Best Surgery Center and Best MediSpa - Business Wire - November 10th, 2021
- Allergan Aesthetics | An AbbVie Company - November 10th, 2021
- Ocular Therapeutix Reports Third Quarter 2021 Financial Results and Business Update - Business Wire - November 10th, 2021
- FDA Approves Xipere Eye Injection from Bausch and Clearside - InvisionMag - October 30th, 2021
- Aesthetic plastic surgery practice offers the first and only FDA-approved injectable for cellulite - WIBW - October 30th, 2021
- Know the Symptoms of Thyroid or Graves Eye Disease - AARP - October 18th, 2021
- FDA Approves Dextenza for Use in Patients With Ocular Itching Associated With Allergic Conjunctivitis - Pharmacy Times - October 18th, 2021
- Plastic surgeon to celebrities explains every tool she uses - Insider - October 6th, 2021
- BMP4 and inflammation cytokines | JIR - Dove Medical Press - August 21st, 2021
- Dysport 101: Everything to Know About the Fast-Acting Neurotoxin - NewBeauty Magazine - August 21st, 2021
- Elise Hu: The Beauty Ideal - KUAR - August 21st, 2021
- Al Ain's hospital achieves another milestone after performing complex brainstem operation - Gulf Today - June 29th, 2021
- Intense pulse and LLL therapy in meibomian gland dysfunction | OPTH - Dove Medical Press - June 29th, 2021
- Im A Neuro-Ophthalmologist: Here Are 5 Ways To Support Your Eye & Brain Health - mindbodygreen.com - June 12th, 2021
- I Used Makeup to Hide My Asianness Here's Why I Don't Anymore - POPSUGAR Beauty Austrailia - May 31st, 2021
- From ancient Egypt to Beverly Hills: A brief history of plastic surgery - CNN - May 31st, 2021
- How I Learned to Love My Monolids - Vogue - May 31st, 2021
- Plastic Surgery was Buoyed by the Zoom Boom but the End of Social Distancing Offers Patients a New Incentive to Get Started on Procedures, says Dr. J... - May 19th, 2021
- Is Fat Transfer the Future of Anti-Aging? This Expert Says Yes - NewBeauty Magazine - April 22nd, 2021
- The art of gifting tea | Lifestyle Gulf News - Gulf News - April 5th, 2021
- Podcast: In the AI of the Beholder - MIT Technology Review - April 5th, 2021
- Brewed with innovation | Lifestyle Gulf News - Gulf News - April 5th, 2021
- 6 Things You Should Know Before Getting Double Eyelid ... - March 9th, 2021
- Why does Yesung need surgery? Worried fans say Super Junior with you hurt isnt what we want before comeback - MEAWW - February 10th, 2021
- Beauty standards are rooted in whiteness | Opinion | dailytitan.com - The Daily Titan - February 10th, 2021
- Eyelid - Wikipedia - February 1st, 2021
- Surgery for Double Vision in Adults | NYU Langone Health - February 1st, 2021
- Double Vision Causes, Tests, Treatment & Symptoms - February 1st, 2021
- Eye Muscle Surgery - procedure, recovery, blood, pain ... - February 1st, 2021
- Perfect Eyes Ltd | London's Leading Cosmetic Eye Surgeon - February 1st, 2021
- What to Expect After Strabismus (Eye Muscle) Surgery ... - February 1st, 2021
- Plastic Surgery Trends According to Two NYC Experts - DuJour - dujour.com - February 1st, 2021
- These are the Prettiest Idols with Monolid and Double-Eyelids, According to a Plastic Surgeon - Kpopstarz - January 23rd, 2021
- Natural, needle or the knife? How stars from J-Lo to Katie Price got their looks - SamfordCrimson News - The Samford Crimson - January 22nd, 2021
- Here's Everything You Should Know About The K-Pop World - Man's World India - December 28th, 2020
- Expert in Asian Eyelid Surgery Now Operating in Southern California at WAVE Plastic Surgery - PR Web - December 22nd, 2020
- Sharp rise in surgery for dog bites with 3,000 people needing surgery last year - Daily Express - December 21st, 2020
- Types of Double Eyelid Surgery (Don't be Fooled when choosing) - December 13th, 2020
- Plastic Surgery in the Age of the Pandemic: Heres Why Its on the Rise - Vogue.com - December 3rd, 2020
- Update on the latest sports - Newscenter1.tv - November 28th, 2020
- Latest in sports - The Advocate - November 28th, 2020
- BlackRock Throgmorton Trust Plc - Total Voting Rights - Yahoo Finance UK - November 26th, 2020
- Skipping cross the creek - Mount Airy News - November 22nd, 2020
- Double Eyelid: Surgical & Nonsurgical Options, Pictures ... - November 2nd, 2020
- Heres What Idols Go Through When They Get Double Eyelid ... - November 2nd, 2020
- 'You might think the 'fox eye' look is just a beauty trend. This is why it's so triggering.' - Mamamia - October 31st, 2020
- You look Familiar Instagram Face and the De-racialization of Beauty - SWAAY - October 30th, 2020
- World Series 2020: How the Dodgers built their NL champion roster through trades, free agency and the draft - CBS Sports - October 21st, 2020
- East Asian blepharoplasty - Wikipedia - October 2nd, 2020
- The Dark History Behind Double-Eyelid Surgery - October 2nd, 2020
- How Much Does Double Eyelid Surgery (Asian Blepharoplasty ... - September 12th, 2020
- Potential Positive Readout Of Aurinia Pharmaceuticals' Phase 2/3 AUDREY Trial Could Bring Best-In-Class Eye Drops For Dry Eye Syndrome - Seeking Alpha - September 9th, 2020
- PSA: Be Extra Careful When Youre Trying To Open A Vacuum Flask That Is Feeling Uncommonly Tight - The Rakyat Post - August 21st, 2020
- The 'fox eye' beauty trend continues to spread online. But critics insist it's racist - NewsDio - August 18th, 2020
- For black lives to matter, all looks must matter - The Times of India Blog - August 17th, 2020
- The 'fox eye' beauty trend continues to spread online. But critics insist it's racist - CNN - August 12th, 2020
- Covid19 Impact on Asia Pacific Aesthetics Market 2020- Global Trends and Regional Forecast to 2023 - 3rd Watch News - July 15th, 2020
- Fans rally behind Grace Chow and her surgical scars - The Star Online - July 15th, 2020
- The Dark Side of K-Pop Was What Drew Me to the Genre - Allure - April 21st, 2020