Dr. Chester Oddis, a founding medical advisory board member of TMA, answers questions about the most ambitious study ever undertaken for a myositis drug. The RIM study focused on Rituximab in treating adults and children who have dermatomyositis or polymyositis. Dr. Oddis, who was the lead investigator for the multi-center study, is a professor of medicine in the department of Rheumatology and Clinical Immunology at the University of Pittsburgh and the director of the fellowship training program there. He has written extensively on the diagnosis and management of patients with myositis.
"There is some confusion about "Rituxan" and rituximab. Rituxan is a brand name for rituzimab, which is the generic name."
Aisha Morrow, TMA: We're very lucky to have Dr. Chester Oddis with us today. Dr. Oddis, a long-time friend of TMA, is an internationally-recognize authority. He was on the original medical board for TMA, is a current board member, and has participated in research and published studies that have greatly advanced the worlds's understanding of the nature, diagnosis and treatment of myositis. Today, Dr. Oddis answers questions about the "Rituximab in Myositis (RIM) Study," the most ambitious study ever undertaken for a myositis drug. The RIM study focused on Rituximab in treating adults and children who have dermatomyositis or polymyositis. Dr. Oddis, who was the lead investigator for the multi-center study, is a professor of medicine in the department of Rheumatology and Clinical Immunology at the University of Pittsburgh and the director of the fellowship training program there. Please Welcome Dr. Oddis
Dr. Oddis: Thank you.
TMA Member: I had some Rituxin treatments in 2005 to address very low blood platelet counts. Two and one-half years later I was diagnosed with Inclusion Body Myositis (IBM). What other conditions are treated with Rituxin? Could the Rituxin treatments have triggered my IBM condition?
Dr. Oddis: Rituximab is used to treat lymphoma and many other hematologic and autoimmune conditions. The list is quite long. There is no data to support its use in IBM and I would not recommend it. IBM is much different than PM or DM
TMA Member: What are the side effects ? Pls don't say none. All medicines have some.
Dr. Oddis: For me to outline the "potential" side effects would take several pages. The answer to this is available on the American College of Rheumatology website on medications and it is pasted below.
TMA Member: I have used rituxan with methotrexate on board for several years with great results. I have recently quit taking the methotrexate with the advice of my rheumatologist since most symptoms have diminished. Will the rituxan work on it's own? I am scheduled for another infusion in February.
Dr. Oddis: It may work on its own without the need for mtx, but some have reported that the concomitant use of mtx increases the effectiveness of rituximab. I think it is fine to adminster the rituximab alone at the next infusion.
TMA Member: I have had four(4) treatments of rituximab of twice each time spaced two weeks apart, with relapses between each. My last treatment was 18 months ago and I am currently without symptoms or adverse test readings. Should I consider a maintenance treatment or merely continue periodic testing until either symptoms or test results begin to worsen?
Dr. Oddis: We don't know the answer to this question. I don't usually give maintenance therapy and there is controversy, even in the rheumatoid arthritis literature, as to whether maintenance therapy is indicated. Since you have responded to the treatments my opinion is to administer the rituximab at the first sign of relapse.
TMA Member: I'll start with a brief histoy, diagnosed in 2007 with polymyositis/mixed connective tissue disease CK 13000 with significant weakness. Went from full time labor nurse to bedridden at home in hospital bed. I am now 64yrs old. I have been treated with prednisone (currently taking), methotrexate ( stopped because of elevated liver enzymes), azathioprine (stopped because of neutropenia), currently on IVIG 80 grams daily x 3 days every 6 weeks which controls symptoms and CK.
I am very aware, though of when my dose is due i.e.: harder to get off chairs less stamina etc. My doctor recently added cellcept, but is worried neutropenia may again develop. My doctor is also concerned insurance will deny IVIG soon ( been on it 2 years). With all of that in mind Rituxan may be my next option. My concern with it are side effects. Am I at increased risk because of age? risks of activating the JC virus?? Is it worthwhile to be tested for the JC virus prior?? Is knowing if someone is Anti SRP positive worthwhile in perhaps determining if my case is in that resistant category which Rituxan may help? Thank you for your time.
Dr. Oddis: I believe rituximab is a reasonable option in your case but it seems to me that damage of muscle may also be an issue in your case. However, if you are responding to therapy then this indicates some level of disease activity that may still be responsive to therapies.
The risk of PML is incredibly low. There is no routine testing for the JC virus that is being done in patients but I suppose if it is negative in your blood now that may put you at lower risk.
Knowing if you are anti-SRP positive may provide some help in assessing response and it would help to verify the accuracy of the diagnosis. However, if you have MCTD and if the anti-U1RNP is positive then it is unlikely that you have the anti-SRP autoAb.
TMA Member: I wonder if there is any aspect, even minor, regarding this study that might be of interest to those of us with IBM. Otherwise it would be of only academic interest.
Dr. Oddis: All IBM patients were excluded from the RIM Study and there is little to no data on treating IBM patients with rituximab outside of the RIM Study. I really have no good reason to believe that this treatment with help IBM patients.
TMA Member: I have dermatomyositis with ILD. How has this Rituximab helped with patients who have ILD?
Dr. Oddis: This is an important area to study and many of us are interested in ILD so we always want to know about new therapies in myositis-associated ILD. However, at this time we do not have enough data regarding the response of the lung to rituximab in the RIM Study patients. This may be looked at further in the RIM patients but there only a few patients with significant ILD in the RIM Study.
TMA Member: Hello I dermatomyositis for almost 12 years I have never used rituximab, but once only infliximab and I had anaphylactic shock reaction. Can I try rituximab?
Dr. Oddis: Even though you had a reaction to infliximab you can still try rituximab and it does NOT mean you will have a bad reaction to the rituximab.
TMA Member: I read that there seems to be a particularly strong effect of rituximab for those with anti-Jo-1 antibodies. Could you please discuss this impact further.
Dr. Oddis: The only thing that we can say now is that the presence of anti-Jo-1 autoantibodies predicted a beneficial response to rituximab so if a patient has this marker then there is better chance of responding to the drug than if they did not have this marker in their blood. The impact of this after the data is peer-reviewed is that this is the most common antibody marker in myositis so it affects a lot of patients.
TMA Member: What range should various measures of myositis show before trying a new treatment?
Dr. Oddis: I'm not sure that I understand this question. The indications to begin or change treatment vary from patient to patient. That is, if your disease is flaring by increasing muscle weakness combined with elevated muscle enzymes (blood CK levels) then this is often an indicator to begin treatment or change the treatment you are currently receiving.
TMA Member: I am a 73 year old female diagnosed with polymyositis in 2002. I have had 14 infusions of Rituxan in the past 4 years in addition to prednisone and cellcept medications. Muscle strength is continuing to deteriorate. With the start of IVIG octagam infusions in October 2012, can I expect any benefit from continuing the Rituxan?
Dr. Oddis: If you are saying that the rituximab infusions did not improve your strength, then I am not sure why you are continuing to receive them. Do you have PM or IBM? Personally, I would not continue rituximab if IVIg is being started, but I don't know the details of your case.
TMA Member: Dr. Oddis, my wife who has PM, received her first and only infusions of rituximab in June 2011. Now, eighteen months later, her CPK is still holding well under 120. She takes a combination of daily azothioprine and once per week methotrexate. She currently takes no prednisone. We are very pleased with these good developments. My question is: What is the average length of time for the rituximab to continue working in relatively healthy 56 year-old women?
Dr. Oddis: That is difficult to say but her response is encouraging and I would not adminster the drug again until there is a flare. We have long term responses in some patients.
TMA Member: i have had polymyositis for 4 years now. i have taken prednisolone, methotrexate, azathiopine, mycophenolate mofetil, mycophenolate sodium and IVIG. Last year around November i had a relapse and my doctor asked me to take rituximab. I refused taking and after a while I picked although I still walk with a walking aid to enable me climb stairs but now my muscles I weak its almost difficult for me to get up from a chair. Do you think i need to take rituximab and if i do will it take care of the muscle weakness and prevent me from having another relapse?
Dr. Oddis: IT is too difficult to predict the response in your case. Are we sure this is PM and not IBM.
TMA Member: Dr. Oddis, I am a 65 year old male diagnosed with IBMs in 2009 by biopsy. Is there any connection between s-IBM and Lyme disease. I spent much time in the outdoors most of my life.
Dr. Oddis: There is no connection between Lyme and IBM that I am aware of.
TMA Member: Is this drug good for people who have an overlap of dermatomyositis (skin problems) and Lupus?
Dr. Oddis: I think it would be fine to consider using rituximab in your case but there is no specific data available.
TMA Member: Hi Dr. Oddis, I was a subject in the RIM study and had considerable improvement of DM symptoms after receiving Rituxan in 2008. I was re-treated during a relapse in 2010 and my muscle strength improved again, but I had a severe SJS-like skin reaction. Now that I won't be able to take Rituxan again, I'm interested to know your expert opinion on current treatment options I should consider if necessary. Thank you so much for continuing your active role in TMA and taking time to answer our questions today.
Dr. Oddis: First let me thank you for allowing us to enroll you in the study - we appreciate that. Other options include cellcept for skin and there are many possibilities such as combination of methotrexate/imuran, IVIg etc.
TMA Member: I was wondering if any study has been done to see if going on a gluten-free diet can alleviate the adverse symptoms from Dermatomyositis and Polymyositis of which I'm experiencing both ailments since 2008. I'm asking because I've read going on a gluten free and/or even vegan diet has helped other immune problems like Lupus and Sjogren's Syndrome (both of my siblings suffer from one of these symptoms). I did my own test since July and noticed a difference. Not only did I drop 20 lbs but my finger tips didn't profusely cut and bleed but started to heal. It didn't heal completely but I noticed some relief. Also my breathing seemed to stabilize (Polymyositis affects my lungs). I'm currently on 2000mg Cellcept, 5 mg Prednisone and 400mg/80mg Bactrim. I'm a 54 year-old Asian female.
Dr. Oddis: Unfortunately, there are no good studies on this intervention. I wouldn't be surprised to know that some pts improve and this is a benign thing to do.
TMA Member: I'm a yoga teacher suffering from Dermatomyositis where it affects my fingertips (constant splitting/peeling of skin to the point it bleeds). It's so bad that I have to wear the medical gloves or finger tip latex covers throughout the day and evening hours to keep the cuts from being exposed to the air as the band aids just keep falling off. One of my students (from Bosnia) brought me a tube of Flogocid mast which you can only get from there. She said to try putting it on my finger tips to see if it alleviates the problem as it has helped her with other skin problems. I have to say that it does give me relief. The finger tips stay moist instead of drying, splitting, cracking but it requires me to use it all the time but I don't want to because I read that this cream was actually for vet medicine and not for human use. Yet, if you read the blog for this cream, many have said it has helped them. Just curious if you have ever heard of this cream. http://www.flogocid.com/what_is_flogocid.html
Dr. Oddis: I have not heard of this cream.
TMA Member: I have PM/ILD for 2-1/2 years. I take 3mg prednisone every other day and 2,000 mg of Cellcept. Is Rituximab recommended for ILD over IVIG? Is Rituximab the same as Rituxan? If the ILD were to get worse, do you add this drug as a 3rd line drug or replace Cellcept? Thanks so much!
Dr. Oddis: The drugs are the same. I think using ritux for ILD makes more sense than using IVIg so I would consider adding it as you suggest.
TMA Member: Why isn't this treatment also effective for Inclusion Body Myositis?
Dr. Oddis: What works for PM and DM does NOT work for IBM - it is essentially a different disease and I've never been convinced that I have imiproved any IBM pt that I have treated.
TMA Member: When would rituximab be recommended in treating PM if I have been successfully treated thus far with methotrexate? I know that I could have potential liver side effects under current treatment. Are there any side effects possible with Rituximab? Thank you.
Dr. Oddis: Ritux would not be indicated in your case since you have done well with mtx. I would stick with the mtx as the side effects may actually be less.
TMA Member: I'm a patient who has had 51 IVIG treatments over the past 6 years at 1.6g/kg body weight plus methotrexate and sometimes plus low dose prednisone. CK is 1300. The rashes for my dermatomyositis look most like anti-Mi2 but the auto-antibody test has not been done. We're now going to try rituximab. Hopefully rituximab on its own will be enough. Questions: 1. If necessary, can IVIG and rituximab be used together? 2. If so, what would be the timing of the doses? 3. Would full doses be used?
Dr. Oddis: Personally I would not combine the IVIg with ritux and would see what the ritux does alone. However, some of the dermatologic responses have not been as good to ritux.
TMA Member: Is there any medication for IBM? I am 77 female and getting really difficult to walk. Fell 2 weeks ago hit my head on cement wall. Lower back very painful.
Dr. Oddis: Nothing that I know of works for IBM
TMA Member: I have been taking Rituxan every 6 months as treatment for DM, along with prednisone, starting in February 2012. Is there any way to know if Rituxan is safe to use as long-term primary treatment (for years to come)? Or does the risk for PML or other side effects increase with each treatment? How safe is Rituxan as a long term treatment for DM?
Dr. Oddis: We simply have no data to answer that question.
TMA Member: There has been a lot of publicity recently about some work done at the McGowan Institute at the University of Pittsburgh involving muscle regeneration. The work involves implanting an extracellular matrix where muscle growth is needed. The matrix attracts the body's own stem cells which cause regrowth of the lost muscle cells. Do you think this could have implications for treatment of myositis and other muscle diseases?
Dr. Oddis: Too difficult a question to answer at this point and much too early at this time.
TMA Member: There was no response for the app so I am resubmitting my question. I have read about successful muscle regeneration done at the McGowan Institute at the University of Pittsburgh. An extracellular matrix is inserted where muscle growth is needed. The matrix attracts the body's own stem cells which replace the muscle which was lost through injury. This has worked in cases where severe muscle loss left the patient seriously disabled. Could it be used for muscle diseases such as myositis?
Dr. Oddis: see answer provided
TMA Member: How long should the conventional treatment of prednisone and Methodrexate be continued before trying rituximab? Example: after one year of treatment,I am now down to 10mg. prednisone and 7.5 methotrexate.
Dr. Oddis: If the response is good to mtx then don't change the therapy. Ritux is often difficult to get approved so there may have to be other therapies used first.
TMA Member: Hello, I have had PM for 4 years. At my worst my CPK was 9500 and I couldn't even roll over in bed. I was on high doses of prednisone that did nothing. Imuran made me very sick. About 18 months ago I started taking IVig and it has been a near miracle. I can function again. But I still have trouble getting out of chairs, off the floor, and up/down stairs. My CPK is running between 600 and 900. My rheumy thinks I can be even better if I switch to Rituxan. I am scared of the Rutuxin and its side effects and wonder if I should continue to be happy on IVig. My question is, what are the risk/benefits of Rituxin and have you seen significant improvements in individuals who were receiving good results from IVig?
Dr. Oddis: If the respons to IVIg is good then that is encouraging. I would agree wth your rheumatol. that a swithch to Rtx should be considered. You can review the side effects on line or with them.
TMA Member: Will there be RIM trials in CA?
Dr. Oddis: The trial is completed.
TMA Member: I have heard patients in remission after Rituxan. What % of patients end up in remission after Rutixin? How many treatments necessary to end up in remission?
Dr. Oddis: There is simply not enough data to answer this question but total remmision is unusual.
TMA Member: Dr. Oddis, Does this drug help relieve the pain, itching and sores which are a result of the derma part of myositis?
Dr. Oddis: The skin response to rituximab has not been as encouraging to date.
TMA Member: Hi Dr. Oddis,
Is there evidence that rituximab improves lung function in patients with polymyositis related interstitial lung disease?
Dr. Oddis: A very important question but one that we are not able to answer as yet. My hope is that it will improve the ILD.
TMA Member: How successful has rituximab been for patients who do not do well on prednisone and relapse? Thank you for ALL your hard work and sacrifices on our behalf.
Dr. Oddis: I think the initial results are encouraging for those that relapse.
TMA Member: Is there a difference between rituximab and rituxan?
Dr. Oddis: No, same drug.
TMA Member: Dr Oddis, if necessary can rituximab treatment be combined with IVIG treatment? Would the full doses be used of both or reduced doses?
Dr. Oddis: Not a common combination to be used except perhaps in children. And I doubt insurance will cover both.
TMA Member: Dr Oddis, is there a way to view an executive summary of the study?
Dr. Oddis: Not sure what you mean but the study will be published in its entirety within next couple of months.
TMA Member: How long should I stay on Prednisone/Methotrexate combo treatment before trying rituximab?
Dr. Oddis: Very difficult to say if response has been good to pred/mtx. Insurance coverage may also be an issue and there are other things to try first.
TMA Member: Can you address why some insurance companies will not pay for rituximab ?
Dr. Oddis: Unfortunately there is no good answer. This is a very expensive form of treatment.
TMA Member: I have had DM for three years, took prednisone and methotrexate for last three yrs. Finally off both. been taking imuran for last year, still on it 150mg/day together with IVIG for last year. IVIG helps. I am stable. My doctor does not do CPK tests. Is that ok? He feels my strength and says I'm doing well, I feel the same. At what point should I consider Rituxan. Has Rituxan worked DM patients out of any more drugs who are basically in remission?
Dr. Oddis: Do not use ritux if doing well.
TMA Member: I have Antisynthetase Syndrome with polymyositis and ILD. I am currently waiting for approval to go on Rituximab. I have heard that the potential severe side effects possible with this drug are less prevalant when used on the autoimmune diseases as compared to it's use on other diseases. What is your opinion on this?
Dr. Oddis: The chance of serious SE in your case are not that high. That is good you were approved.
TMA Member: Can you summarize your study? I am told that I'm in a crossover stage from PM to IBM. Diagnosed 4/10/2010. Thanks for all you do!!
Dr. Oddis: Will be available for review in next 2-3 months. Too complicated to review in this setting.
TMA Member: Dr Oddis, when is it appropriate to consider using Rituxan for treatment of PM and DM? Would it be used after trying normal treatments like prednisone, imuran, methotrexate, and even IVIG? Or are there indications that would make Rituxan the treatment of choice?
Dr. Oddis: It should only be considered after standard therapies fail so it is more like a 3rd line of treatment at this point.
TMA Member: How does Rituxan work in myositis patients? Is this something that a PM patient would have to take for the rest of their lives? What can one expect for results taking the drug?
Dr. Oddis: It depletes one type of immune cell, the B cell. You would not necessarily continue this treatment the rest of your life.
TMA Member: Not sure if this question was submitted in time...so please bear with me to re-submit. I have anti-syntetase syndrome with ILD, also very poor reaction to even low doses of prednisone and have relapsed twice. Dr. is considering rituximab as next course of treatment. Is this a good idea? MANY thanks for your sacrifices and hard work to help all of us!
Dr. Oddis: I think it is reasonable to consider ritux in your case given the dx of antisynth syndrome and the fact that you have failed conventional therapy.
TMA Member: Dr. Oddis, would myositis patients be able to try one infusion of Rituxin instead of two per treatment as I read RA patients may try?
Dr. Oddis: I would not recommend just one infusion.
TMA Member: What considerations should a DM/PM patient make when deciding with their doctor if rituximab or IVIG is the better option for treatment when other treatments fail?
Dr. Oddis: Very difficult to provide brief answer to this. Depends on previous therapies, severity of myositis and many other factors.
TMA Member: Hi Dr. Oddis, my husband is a 56 year old man diagnosed with PM, Anti-Jo 1 in 2009. He was on prednisone and Cellcept. His muscle enzymes are good, but lung function is deteriorating. He has been on Cytoxan for the last 2 months and lung function continues to deteriorate. DLCO in Feb 2012 was 70%, yesterday it was 43 %. Do you think it is at least worth trying rituximab to improve his lung function?
Dr. Oddis: I would consider ritux in this case.
TMA Member: Would you say that in most cases Rituxan to be better, longer lasting than IVig for DM for a 40yr male?
Dr. Oddis: Yes
TMA Member: Dr. Oddis, based on the questions there is much discussion about PM and other muscle disease but not much about DM. Is this drug used solely for DM or must the muscles be involved also?
Dr. Oddis: The data is not as good for ritux being effective in the skin rash alone.
TMA Member: Doctor, I am doing well on IVig but not completely in remission. I still have CPK 600-900, and still have problems in getting out of chair, stairs, etc. Since IVig has improved me significantly, should I stay with it or see if RituxAn would make me even better?
Dr. Oddis: If there is still active disease then you may get an added benefit from ritux
TMA Member: I was recently diagnosed with CADM after a year-long skin flare. I am on prednisone and tapering to plaquenil. I had a similar CADM flare 8 years ago after the birth of my first child, and it spontaneously resolved after one year (after I weaned, no meds). How often do you see spontaneous remission in CADM? Also, I am also allergic to nickel and have noticed the DM rashes on my hips are associated with/aggravated by metal grommets on jeans. Is there any correlation between metal allergies and DM? Could metal allergies be the cause of the chronic inflammatory state?
Dr. Oddis: I doubt that this is the case.
TMA Member: I have had PM for five years, am currently in remission except for residual interstitial lung disease which at times is quite debilitating. Prior treatments of rituximab always cleared this up. Should I consider a treatment for this reason alone?
Dr. Oddis: Yes, that is very interesting that your lung disease responded. would consider this again.
TMA Member: What does the acronym PML mean?
Dr. Oddis: Progressive Multifocal Leukoencephalopathy
TMA Member: Hello Dr Oddis, I was diagnosed with Antisynthetase Syndrome and BOOP last year. My doctors decided to treat the BOOP first with prednisolone, which took a year. Since mid September this year, I've been on an immunosuppressant (Imuran) to treat the antisynthetase syndrome. My condition has worsened since with more intense and prolonged joint stiffness and pain, muscle inflammation and weakness, and frequent appearance of "mechanic's hands". My rheumatologist mentioned in passing rituximab as a possible treatment option. Would rituximab help in my case of antisynthetase syndrome? If it would, what exactly would it do?
Dr. Oddis: I would agree with your doctor that ritux should be tried.
TMA Member: Can you give any conclusions of the study today?
Dr. Oddis: Will be available for review within next couple of months as it accepted and in press.
TMA Member: Low long after a Rituxan infusiuon should a patient know if it has been effective or not? Is two infusions still the standard treatment?
Dr. Oddis: A bit unpredictable but probably within 3 months.
TMA Member: Dr. Oddis, I've had PM, probably since 2000, but diagnosed 2008. Sjogren's also probably since 2000, but diagnosed 2005. Currently on Hydroxcloroquine, 200 mg/daily, and methotrexate injections, 0.4 cc/weekly (I think it's about equal to10 mg). Believe my CPK is in normal range, though still have significant muscle weakness, Last muscle testing was "stable" per neurologist. What would you think about my going off methotrexate as a trial? My rhumatologist says not a good idea, but what do you think? I know this question isn't about rituximab specifically, but just a treatment question, if you don't mind.
Dr. Oddis: I think it is always reasonable to try something like this but do it jointly wiht your doctor
TMA Member: Dr. Oddis, Is rituximab used in conjunction with other drugs or is it a treatment used by itself?
Dr. Oddis: It can definitely be combined with other agents like methotrexate, imuran and others.
TMA Member: Have there been any positive effects of rituximab on those with ADM? Is there any indication that a negative response to IVIG (asceptic meningitis twice) may mean a negative response to rituximab?
Dr. Oddis: Not as encouraging to treat the skin problems and no indication that negative response to IVIg indicates poor response to ritux
Aisha Morrow, TMA: TMA would like to extend a special thanks to Dr. Oddis for being with us and graciously spending the time to answer your questions. This concludes today's discussion. Thanks to all the members who participated today.