on September 05, 2013
Dr. Andrew Mammen is the Co-Director of the Johns Hopkins Myositis Center and an Assistant Professor of Neurology at Johns Hopkins School of Medicine. He is also a member of TMA’s Medical Advisory Board and the author of many myositis studies.
Aisha Morrow, TMA: We are honored today to present Dr. Andrew Mammen for a live discussion. Dr. Mammen is the Co-Director of the Johns Hopkins Myositis Center and an Assistant Professor of Neurology at Johns Hopkins School of Medicine, He is on TMA’s Medical Advisory Board and will be a presenter at TMA’s Annual Patient Conference. Today he answers your questions about “When myositis doesn’t respond to treatment.”Please ask questions that may be of interest to everyone, and do not submit the same question multiple times, as that makes the whole process take longer. Welcome, Dr. Mammen, and thank you for being a part of TMA’s live discussion series.
Dr. Andrew Mammen: This is Dr. Mammen and I will do my best to answer your questions.
TMA Member: Hope you can respond to my question. I was diagnosed 26yrs ago with DM/Lupus and trialled on most immuno-suppresants , also IVIG and Plasmapherisis. I was sensitive to most drugs and told that Acthcar would probably give me same negative effect. I wrote on the forums back in 2007 that my Specliast had attended a conference in the UK and let me try Intravenous Magnesium over a four day period. The results were amazing but unfortunately temporary. I had the opportunity to see him last week and he is using it in his clinic for pain management. I had 30mg over a thirty min period IV. Again the results were great. They have found since my first infusion that the results are cumulative over a longer period. I would be interested to know if there are any studies being done in the US on Magnesium as it is cheap and has very few side effects. A bit of hot flushing and the only down time was a couple of days of fatigue. That may have been from the trip to see him. He is an Anaesthesist with a specialty in Pain Management and has always been interested in me as a patient. He also mentioned some new research associating us with Lyme Disease. Can you please comment as my Myositis has not responded to any treatment.
Dr. Mammen: To the best of my knowledge, there has been no good clinical trial showing that Acthar works well for DM. I would be in favor of a trial of Acthar in myositis before prescribing it. In my opinion, it may not work better than prednisone.I have not heard of using magnesium to treat myositis and I would not expect it to control autoimmune disease. Not sure about using it for pain management – have not heard of that either.Rituxan would be another treament to consider for refractory DM.
TMA Member: Good Day Dr. MammenI was first diagnosed with Dermatomyositis in Sept 2007 after a large muscle Biopsy because of my physical condition, blood work, and all the muscle and most skin signs. In 1991, I was misdiagnosed with RA and in 2002 the first DM signs showed up and baffled my doctors. Since 2007, I have not had a remission and it has only been 5 years tot IVIG that brings down the CPK and other associated bloodwork down to normal for a short period of time and the steroids and IVIG is continued with the MTX injections. Recent MRI done on knees and ankles revealed arthritis in joints and bone marrow edema. The orthopedic surgeon did not recommend surgery for me because of my overall poor physical condition, immune system issues, and the surgery could kill the bone as well as I would more likely get an infection and cause the immune system to adversely impact my life. Now, my question would be do I actually have RA along with the DM, Sjogren’s, and Raynad’s?????! Or do I just add Osteoarthritis? Lungs are also affected.
Dr. Mammen: It’s hard to know without seeing you and evalutating your medical records whether you have all, some, or none of these conditions. However, many patients with DM also have other autoimmune conditions, including those that you have been diagnosed with.
TMA Member: I am newly diagnosed with IBM. I was wondering if there were any new protocols? I have heard of Gene Therapy.
Dr. Mammen: Unfortunately, there are no proven medical therapies available for IBM. We are hopeful that Novartis will intiate a large multicenter clinical trial of a new agent for IBM that I understand performed well in a small single center trial (this has not been published to the best of my knowledge).
TMA Member: Dear. Dr. Mammen,I have been a DM patient since 1994. The on set was quick and involved extensively. Most likely due to being pregnant. I did not respond well to many of the treatments the doctors prescribed. I finally did respond to IVIG, and used that for many years. After a fall a few years ago, i have lost strength and energy and have not been able to come back from it. The IVIG, Rituxin, and Orencia that they had me try has not worked. Also the doctors now believe that I actually have JDM. Have you used the new/old drug Acthar? I was going to bring it up to my doctor at Dartmouth Hitchcock. Do you have other suggestions
Dr. Mammen: Sorry to hear about your condition. To date, Acthar remains unproven as a treament for myositis. I would like to see a clinical trial of this medication for myositis.In patients with refractory DM, the question is: do you have permanent muscle damage that more aggressive treatment may not improve? Or is there active disease we should be treating? A muscle MRI may help answer these questions.
TMA Member: It appears that testosterone and other “illegal drugs” have helped athletes with strength and muscle size. Could not the same be true for sufferers of inclusion body myositis?
Dr. Mammen: If there is testosterone deficiency, I would recommend testosterone replacement therapy. Otherwise, I would probably avoid using testosterone or illicit hormones for IBM and other forms of myositis.
TMA Member: Good Afternoon, My doctor is thinking about adding Achtar to my current treatment of IVIG. IVIG is working but he would like to see me back to near normal (my CPK levels are around 800 and I still have trouble with my legs). What is your opinion of Achtar?
Dr. Mammen: Please see previous answers about Acthar…
TMA Member: Is it expected that there will (to some extent) be some kind of a correlation between the myositis autoantibodies in a patient and which medications are most likely to work?Is anyone formally studying this?
Dr. Mammen: We don’t know much about this and it should definitely be studied further.The evidence is not terrific, but it may be that patients with anti-SRP antibodies respond well to Rituxan. And anti-Mi-2 patients may respond well to relatively minimal immunosuppressive therapy. However, each patient is different…
TMA Member: Can myositis autoantibodies be tested in patients currently receiving IVIG (or other drugs) with reasonable reliability?
Dr. Mammen: Yes, although there is a small possibility of a “false positive” result. I have not actually seen this.
TMA Member: Are we years away or decades away from IBM treatment delivery and what are myositis research centers in Southern California. Tom Landau, Los Angeles support group
Dr. Mammen: Nobody knows for sure. Several drug companies are working on drugs that may be useful for patients with IBM, Novartis being one. Most of these are designed to build up muscle bulk and not to stop the disease. Until we actually know what CAUSES IBM, I think our ability will be limited to develop really effective treatments that could reverse the disease course.
TMA Member: Thank you for accepting this question. I have been diagnosed with myositis for five years. My problem is my diagnosis is not definitive. My rheumatologist diagnosed polymyositis while the physicians at the NIH diagnosed IBM. I am aware that the two conditions require different treatment approaches specifically with drug theraphy. How do you recommend I resolve the diagnosis?
Dr. Mammen: Distinguishing IMB from PM can be tough. And sometimes we initally diagnose a patient with PM who we eventually realize actually has IBM. Usually the difference becomes very clear over time.I would recommend that you see a neuromuscular trained physician and have them test for weakness of your wrist flexors and distal finger flexors. (Warning: not all doctors are good at this!) If you have weakness in these muscle groups and an inflammatory muscle biopsy (even without rimmed vacuoles) it is very likely you have IBM.We would be happy to see you at the Johns Hopkins Myositis Center!
TMA Member: I have DM (Dermatomyositis) with related ILD (Intertisial Lung Disease). I was doing well on Imuran and Prednisone. Had a relapse end of June 2013 and ended up in Critical Care (ICU) in the hospital. I was taken off Imuran, Prednisone increased from 4 mg. to 60mg. (now 50 mg.) and infused with Rituxan. The first two infusions, July 29 & Aug 15 seem to have been well received by my system. I am slowly getting stronger and my O2 saturation is improving. If all goes according to what is expected by my doctors, the third infusion will be given January 2014. My concern is what to do if the third and, I understand the last infusion, does not produce good results.Look forward to meeting you in Louisville.
Dr. Mammen: If Rituxan is working well after the first infusions, I would be hopeful that it should continue to work well. However, sometimes people can ultimately fail any medication. What to do if Rituxan fails in your circumstance is a complex question and would require an in-depth evaluation. But IVIG would be one consideration.
TMA Member: When do the clinical trials begin for BYM338 (bimagrumab)? What are the requirements and how do I sign up?
Dr. Mammen: Nobody I know knows the answers to these very good questions. And I’ve asked around!
TMA Member: My polymyositis does not respond to Cellcept, Imuran, Mex or IVIG what else is it for me to do?
Dr. Mammen: In this circumstance, I always question the diagnosis. Could you have IBM or some other muscle disease that does not respond to immunosuppressive therapy?Most “refractory PM” in patients over age 50 without other symptoms of autoimmune disease (lung, joints, skin, etc…) turn out to be IBM…
TMA Member: I have taken Plaquenil since my DM diagnosis in 2004. When the amount I take goes below 200 mg/day, I start to experience muscle weakness. Will I need to continue this dosage indefinitely?
Dr. Mammen: There’s no way to know for surel. However, if your DM is controlled well on Plaquenil only, you are pretty lucky.
TMA Member: I have had myositis for almost four years. During that time I have been on high levels of Prednisone (up to 60 mg). My specialist has tried just reduction, then reduction with axathiopriine, methothrexate, and mycophenolate in succession. Each time when I get to about 20mg of Prednisone, my ck levels start to rise. Do you have any strategies for getting off Prednisone?
Dr. Mammen: The goal of therapy should be to normalize strength, not normalize the CK levels. In most myositis cases, as long as strength remains normal, I will tolerate elevated CK levels. I have some patients who clearly had myositis, who continue to have CKs in the 1000-2000 range, but are completely strong with no muscle complaints: I don’t treat these patients at all. That being said, rising CK levels do herald weakness in other patients…
TMA Member: Dr Mammen:Diagnosed with DM about 6 years ago, but more likely first symptoms showed up in 2002, but regular doctors could not figure it out. It took a few emergency room visits before I was referred to Gulfcoast Rheumatology in Slidell, Louisiana, and within a few months they figured out what was wrong with me.IVIG helped me the most, but never reached remission, and weakness and pain and overlap diseases of Sjogrens, Raynaud’s, arthritis, and heart disease complicates it. I will be 60 next year. I still work a full time job as an engineer for the Navy, and refuse to just lay down and give up with only 6 years to go for a full retirement.My Rheumatologists basically told me, I am difficult to treat, because of my refusing to go out on dissability, and only resting on weekends. Have you had patients with my frame of mind and difficulty treating them as well? I wonder if this could be a major reason for most of us old folks having such difficulty.
Dr. Mammen: I haven’t found that patients who continue to work are more difficult to treat. Consider Rituxan?
TMA Member: Dear Dr… When do we say that myositis is not responding to treatments ?Thank youHuda / PM
Dr. Mammen: Depends on the drug. Examples: Prednisone should work within weeks. Cellcept may take 6 months or longer to work.
TMA Member: I am currently being taken care of at the VA hosiptal in Richmond, Virginia. Should I also be seen by another hospital? Possibly VCU or John Hopkins? I have IBM and live by myself. I now require additional outside help due to falls.
Dr. Mammen: You should be cared for by somebody who sees lots of IBM patients. UVA and Hopkins would be good choices. If you’re falling, you probably need an assistive device (e.g, rolling walker or scooter)…
TMA Member: Thank you for answering our questions. I am age 66 & have PM, diagnosed in 2009 by biopsy. Also have Sjogren’s – diagnosed 2005. Am on methotrexate 0.4cc 1x/week. Plus Plaquenil (generic). No longer on steriods, thank goodness. It is necessary for me to do yoga & physical therapy (plus walking 1/2 mile 3x/week) & even then I seem to be less able to do things than in 2009. Even with this routine, now it is necessary to use a wheelchair in large shopping malls & so on whereas didn’t need that in 2009. Walking on uneven ground, like brick streets or the lawn, is really fatiguing, but wasn’t so in 2009. The biopsy in 2009 suggested there might be 2 processes going on — one was myositis (PM) but the other might be in the category of IBM. My neurologist said it’d take another muscle biopsy to tell. Also, I’m having skin rashes & dermatologist biopsy came back saying findings were consistent with DM. But again, would need a definitive skin biopsy to tell. The methotrexate seems to be keeping the joint & muscle pain under control (tried going off & didn’t work).The question always comes back — why do more biopsies when there’s no other treatments besides what I’m on & I’m tolerating the current meds fine.So…..at what point would you suggest more biopsies (muscle/skin) to nail down whether it’s some sort of IBM and/or DM? And are there treatments for DM or IBM that would make it worth it?Thank you again!
Dr. Mammen: Hard to answer without seeing you and evaluating your records. I would suggest a second opinion at a center where they see lots of PM and IBM. The Neuromuscular (Neurology) groups at Hopkins, Brigham and Women’s, UVA, Washington Univeristy, UCLA, and University of Washington are all very good (I apologize for leaving other good ones out!).
TMA Member: Thank you for taking my question. I was diagnosed with DM almost 9 years ago. I am doing better than when the disease ignited but I have hit a wall. Prednisone is stuck at 5mg. Methotrexate can’t go lower than 20mg. I was taken off plaquenil but had to go back on it due to the severity of the flare. The itch is unbearable but nothing seems to help. Mayo’s attitude is “that’s the way it is.” Is there anything I can try to ease the itch, calcium deposits, sores. Or is this the way it is?Again, thank you.
Dr. Mammen: Calcinosis is very very difficult to treat – sometimes nothing we do helps.But IVIG would be something to consider…
TMA Member: Is there anything which can be done for the calcium deposits in the arms which are beginning to hurt and making it difficult to do anything requiring putting pressure on the lower arm.Thank you.
Dr. Mammen: Again, calcinosis is a very very tough problem. If individual deposits are particularly problematic, surgical resection can be considered.
TMA Member: Hello Dr. Mammen,I am a 49 year old female with polymyositis and interstitial lung disease. I am currently being treated with leflunomide and a temporarily prednisone. My muscles have responded to treatment but my lungs don’t seem to. I get frustrated because it’s either my lungs or muscles. Do you have suggestions on what can help both?Thank you for considering my question.
Dr. Mammen: Consider azathioprine or methotrexate.
TMA Member: If a person with PM received Predisone, MTX, Immuran and 3 TX courses of IVIG with no success. She was labeled resistive to Tx. She has been seen at Cleveland Clinic who made a Dx. thru numerous test, labs and paraspinal Bx. She has been seen by Dr. Ottis, at John Hopkins and a Neuro Dr. to r/o Pompe disease. Has always been treated by a Rheumatolgist. She has not been receiving any Txs for a few years.My question: 1) Would you say the IVIG txs weren’t continued long enough. Should they be tried for a year or longer?2) Any other suggestions for tx or place or any help.
Dr. Mammen: 3 courses of IVIG is usually all I will try.If we failed at Hopkins to diagnose you, consider Dr. Anthony Amato at Brigham and Women’s. Or Dr. Alan Pestronk at Washington University. Or Dr. Matthew Wickland at Penn State. There are many others…
TMA Member: One of my problems caused by IBM has been difficulty swallowing.I recently had a procedure called cricopharyngeal myotomy, which involves disconnecting a muscle that controls a valve that opens and shuts to control the flow of food between the mouth and esophagus. The muscle is supposed to open just at the right time to allow food to enter the esophagus and otherwise stay closed to prevent regurgitation.I have been greatly helped. Has this procedure been given consideration by doctors who have studied IBM?
Dr. Mammen: We often recommend consideration of this procedure in those who have failed the conventional treatment: esophageal dilation.
TMA Member: When myositis doesn’t respond to treatment, how/what do you suggest to help someone to stay positive and not give up? When do you realize that we’ve truly exhausted all possibilities of treatment and say where do we go from here? Thank you for your time.~Suzanne Diagnosed w/PM & DM since 2008
Dr. Mammen: For patients with “refractory PM”, it’s important to be sure the diagnosis is actually correct. In most cases without other organ system involvement, it’s really IBM.It’s extremely rare to have “exhausted all posibilities”. For example, some patients with really refractory DM have responded to high dose cytoxan (chemotherapy-like dosing).
TMA Member: Hello, Dr MammenI am a retired physician (Infectious diseases) with sIBM.I am wondering if you can discuss Folistatin and bimagrumabIt appears that folistatin is administered directly into affected muscles.The Novartis drug is given Intravenously. This seems to have huge implications for actual treatment of IBM. Thank you
Dr. Mammen: Great questions, but beyond the scope of this short-answer format to fully answer. The short answer is that these drugs may make muscles stronger. However, I would not expect them to reverse the IBM disease course…
TMA Member: I was diagnosed in 2007 with PM confirmed by muscle biopsy ( also have antibody markers for mixed connective tissue). I have been on azathioprine had to stop because of low white count even after dose reduction. Currently on prednisone 35mg daily. Had to stop methotrexate because of elevated liver enzymes ( recently restarted so we shall see) , used celcept with no improvement . IVIG for last 2 years with fair results have ok strength for a couple weeks after infusion but it quickly dissipates . I now am having a big flair CKs 3300 ( my top at diagnosis was 13000) so IVIG was increased to every three weeks from every 4 weeks. Rituxan has been discussed but I am JC virus positive ( test was recommended to be done because of small risk of PML with Rituxan esp with hx of concurrent immunosuppressants. ) . Just wondering your take on being JCV positive and risk of PML with Rituxan. I know most people are not even tested and a great portion of the population is positive… How much have you used Rituxan have you personally seen any cases of PML? Thank You in advance for reviewing our questions.
Dr. Mammen: I have not seen PML with Rituxan in myositis patients, but we do warn patients about the possibility.
TMA Member: I was diagnosed in 2006 with DM. I have been through Prednisone, IVIG, and Rituxan treatments. But none of them have made me feel better or stronger. My Rheumatologist says that my DM is always smoldering under the surface. What new treatments are on the horizon?
Dr. Mammen: How about some old ones: methotrexate or azathioprine for example.
TMA Member: Hello, I am Sandra from Belgium, my mother Marie-Rose has been diagnosed with Inflammatory Polymyositis in 2009. She has received the following treatments:- methotrexate intramuscular 20 mg/week – 2 injections per week for 10 weeks – no improvement- immunoglobulines intravenous 2 g/kg (500 mg/kg, 4 days, monthly) + Solumedrol intravenous (15 mg/kg =750 mg 3 days), + Medrol 32 mg/day. light improvement at the beginning (first month) and then no more improvement. She received 7 months of IVIG treatment until Oct 2012. No positive conclusion. – Azathioprine 75 to 150mg oral from March 2012 till April 2013. No positive conclusion- Cyclosporine 200 mg November 2012 – she showed intolerance to it (oral) – Rituximab 1 g + 1g intravenous in December 2012 – she showed no improvement after 5 month – this was not repeated. CK levels are around 350. She decreased the Medrol to 10 mg / day for the side effect of taking corticoides so much time. The doctor from Belgium derived her to Paris in order to make another biopsy. She is very weak and her weight is 49 kg today. Thank you for your comments on her case.
Dr. Mammen: They should stongly consider that she has IBM. Make sure an experienced neuromuscular doctor checks for wrist flexor and distal finger flexor weakness (classic signs of IBM rarely seen in PM).
TMA Member: Polymyositis w/ILD, Jo-1 antibody. Acute attack with pneumonia, 4/2005. Tried all meds including, methotrexate, rituxin, IGG, cellcept, etc. been on tacrolimus and prednisone for over two years. Prednisone can’t stay below 15mg w/o flare ups. Ck measures flares along with changes I feel. Prednisone has been constant for the entire time from 60 to 12.5. Currently tapering again after flare. Lungs at 44% and declining. Is there anything left to try? Doctor does not see Acthar as a good choice. Thank you.
Dr. Mammen: This is a very tough situation – requires a lengthy evaluation and discussion between you, an experienced pulmonologist, and an experienced myositis doctor. Recommend going to a center that offers this (Hopkins..?)
Aisha Morrow, TMA: This concludes today’s discussion. TMA would like to extend a special thank you to Dr. Andrew Mammen for taking the time from his busy schedule to answer your questions. Thanks to all the members who participated.
Dr. Mammen: Thanks for having me! Dr. Mammen.