Friday, June 20, 2014 12:00 pm – 12:00 pm EST This discussion is archived.

Join us today as we welcome Rohit Aggarwal, MD, MSc. Dr. Aggarwal is an Assistant Professor of Medicine and the Education Coordinator for the Rheumatology Division of the University of Pittsburgh Department of Medicine. He has recently joined TMA’s medical advisory board and had a leadership role in the improvement measurement consensus meeting held recently in Paris. He will be taking your questions today about Rituxan (rituximab), which was the subject of a multi-center myositis trial for adults and children with DM and PM.Dr. Aggarwal has received some of your questions in advance, and will choose those of most general interest to answer. Please feel free to submit new questions in the course of the live discussion. A transcript will be available shortly after the end of the discussion.Dr. Aggarwal, thank you for joining us today.

Ask a Question
TMA:

Dr. Aggarwal:

Thanks for having me here. I will be pleased to answer your questions as best as I can.

  • For Children

    Participant:

    Could you let us know how this drug worked for children in the studies?

    Dr. Aggarwal:

    Yes. There is no definitive studies but we believe it works in kids esp juvenile dermatomyositis. In rituximab in myositis clinical trial we actually saw more definitive improvement as compared to placebo than what we saw in adults.

  • Excercise Regimen

    Participant:

    I have just been diagnosis with DM. Im on prednisone and methotrexate. This is my second month of drugs. I exercise everyday. I do about and hours of stretches and ROM. I then alter do 1 1/2- 1 3/4 miles on treadmill and a couple miles on a stationary bike. Every other day i was doing weights. Only 1 lb. and occasionally trying couple reps of a 2lb. weight. It seems though every time i do weights the next day i dont feel well. should i back off the weights. Also how many times should I exercise a week.

    Dr. Aggarwal:

    You should back of weights. This is early in your disease as your health condition improves you will be do more and then you can add weights to your exercise regimen. 3 days a week is enough. Some ROM and stretching should be done every day.

  • Rituxan and CelCept?

    Participant:

    Thank you for working for all of us with Myositis. I was diagnosed in late Dec. of 2006. I was put on prednisone, then later Imuran, which caused a fever and elevated liver enzymes. I took methotrexate for some time which doctors didn’t think was helping enough. I have been on CelCept for several years, now with Rituxan infusions every four months for almost two years. The doctors have tried to wean me off CelCept several times, but I get very weak after 4 to 5 weeks and have to work my way back to being stronger. I am 73 years old. Does the combination of Rituxan with 1500 MG of CelCept seem reasonable to you? Would a smaller dose of CelCept be good with Rituxan?

    Dr. Aggarwal:

    Unfortunately, we don’t have good data to answer your question correctly. I will try to give you my general impression but it is not based on well-founded facts. If you flare up on decreasing cellcept then I will hesitate to stop it. Rituximab and cellcept are fine if that is what taking to keep your disease controlled, however, we are always worried about 2 strong drugs causing increase risk of infection. So, it is better if your disease can be controlled on lower dose of cellcept like 1000 mg a day and you can try to decrease the frequency of rituximab to every 6 months.

  • Lowering Drug Level in Remission

    Participant:

    Dr AggarwalI am on a combination of Cellcept and Rituximab and it has brought me to remission.My question is 2 part- how long do you suggest being in remission before trying to lower drug levels and is the best way to come off rituximab to increase time between infusions. Thank you for your work with myositis.

    Dr. Aggarwal:

    If you are in remission for 1 year I would try to lower the drug. There is not right way of coming off rituximab. Unfortunately we don’t have good data on it so it is not evidence based currently. I would say if you already have 2 years of rituximab (4-8 doses) and 1 year of remission then try to hold rituximab and watch carefully for disease activity. Re-administer rituximab it if any signs of flare up or worsening.

  • Epigastric Pain

    Participant:

    I have had several Rituximab treatments. About 24-hours after each, i developed severe epigastric pain. I subsequently was found to have evidence of small intestinal bleeding from AVMs (note: iron and ferritin levels also very low with accompanying hair loss). I take Xarelto because of multiple pulmonary emboli from IVIG. What is your experience with Rituximab and GI bleeding?

    Dr. Aggarwal:

    I have not had any case of rituximab with GI bleeding. It may or may not be related.

  • IVIG and Rituximab

    Participant:

    The last I heard, it was still a matter of discussion whether IVIG and rituximab could be used concurrently, different rheumatologists had different opinions as to whether they would support or oppose each other’s effects. What, if any, evidence has accumulated so far for and against using IVIG and rituximab concurrently? Thank you doctor.

    Dr. Aggarwal:

    Unfortunately, not much data on combination of IVIG and rituximab. My opinion (only opinion as no data) that they can be used concomitantly.

  • Two Treatments, IgG

    Participant:

    I have had two Rituximab treatments 6 months apart. Four months after my last treatment my IgG serum is now in the low 600s. My next treatment will not be until October or November depending on my CK results. Could this IgG be a problem? I feel the best I’ve felt in 8 years, and my CK levels are staying just a little above normal. Methotrexate is no longer an option due to liver issues. This treatment is the easiest and has the fewest irritating side effects so I would hate to lose this option.

    Dr. Aggarwal:

    I would say if you are not having any recurrent infections and you need rituximab due to your CPK levels going up or more muscle weakness, then you should get rituximab (after understanding increase risk of infection) and monitor IgG levels. My threshold for IgG level is 500 – that is when I get really worried about IgG levels.

  • Cytoxan vs. Rituximab

    Participant:

    Good afternoon, Dr. Aggarwal…I’m a 55 yr old Asian woman diagnosed with Antisynthetase Syndrome (diagnosed 2013), Polymyositis (diagnosed 2008), Interstitial lung disease (diagnosed 2008), Secondary Sjogren’s Syndrome (diagnosed 2013) and have mechanic’s hands.I’ve tried Imuran and Tacrolimus (Prograf) to no avail. I’m currently on 2000mg Cellcept, Bactrim (400mg/80mg) and yesterday I had to bump up to 20mg from 10mg Prednisone (I was on this level for 6 months before flare up) due to increased CK readings (505) from latest blood work.We tried to bump up Cellcept to 3000mg about 6 months ago but it gave me adverse effects (dizzyness and upset stomach), so we lowered it back to 2000mg.It was mentioned that I try Cytoxan as another possible source to get me off of Prednisone. Since then that doctor has retired and my new rheumatologist recommends Rituximab.I’ve read some of the previous discussions (Dec 2012 with Dr. Oddis) on Rituximab and from what I’m reading, it looks like Rituximab is probably favorable over Cytoxan given I have ILD. What are your thoughts and/or suggestion? Thanks for your time and consideration.

    Dr. Aggarwal:

    I would favor rituximab over Cytoxan. This is not based on any comparison between Cytoxan vs. rituximab, but rather just based on our experience with rituximab in anti-synthetase syndrome.

  • Loss of Energy/Drive

    Participant:

    I have DM and have had 2 Rituxan treatments. My CK levels and muscle strength are much improved, but more importantly I feel my movements are more fluid and less awkward. My question though is…..have any of your participants in the study noticed any mental changes? Through all the brain fog and exhaustion through the last 8 years with lots of changing of treatments, I always got up filled with drive and resolve to get things done during the day. Lately I feel happy, but I seem to chase my tail and not accomplish as much.

    Dr. Aggarwal:

    There has been no reports of mental changes from rituximab as such but has been due to brain infection esp viral encephalitis etc after patient receiving rituximab. If you have developed mental changes just after rituximab then I would be worried about brain infections especially viral and it needs to be investigated.

  • Time to See Results?

    Participant:

    I was diagnosed in 2007 with PM/MCTD in 2007 CK enzymes 13000 at diagnosis with positive muscle biopsy. I have been thru the medication wheel Prednisone,azathioprine,methotrexate, mycophenalate, and IVIG . I have had to stop some of the medications for side effects ie decreased WBCs and increased liver enzymes and some simply didn’t work. I have have never reached a great remission, I have had flares through it all. Currently I am receiving IVIG every 3 weeks with minimal effect ( it was working somewhat up until a few months ago) I had reluctance to do Rituxan just because I was worried about side effects esp the black box warning about the JC virus. My latest flare is a big one having a lot of difficulty at this point even walking much like first after my diagnosis, so I relented and have had my first 2 doses of Rituxan 2 weeks apart. Have not seen much change in my condition but it has only been a few weeks since infusion. My question is there any difference in effect for someone with MCTD and Rituxan I know its prob not been widely studied but was wondering in your experience have you seen it not work? How long and how many doses would you give it? Thank you in advance for your time in answering our questions.

    Dr. Aggarwal:

    For most patients it take 2-4 months to see good response from rituximab. So, you have had that yet. I would suggest to wait and see if you get more benefit in next several weeks. Response to MTCD/PM has not be specificially studied but if the disease is PM predominent then it may respond. Since you have failed so many treatment one thing your doctors should do is to make sure you have correct PM diagnosis. There are several time we see incorrect diagnosis and treatment since many muscle diseases like metabolic myopathy, muscle dystrophy, IBM etc..mimick PM very much.

  • Long Term Side Effects?

    Participant:

    Is this new drug having long term side effects like methotrexate?

    Dr. Aggarwal:

    Rituximab is very different from MTX. So their side-effect profile is very different.Rituximab doesn’t cause any liver enzyme abnormalities or stomach issues Or severe low counts, oral ulceration, hair loss etc like methotrexate can. Rituximab main side-effect is increase risk of infections including severe rare infections and infusion reactions. There are several other side-effects reports but all are very rare. Infusion reactions are mostly mild managed by giving steroids with rituximab.

  • What Side Effects Can I Expect?

    Participant:

    I have PM and IMNM and am scheduled for my first Rituxan infusion next week. I’ve been taking prednisone, methotrexate, Imuran and IVIG but have recently stopped metho. My doctors at Hopkins think I will probably stop IVIG once I start Rituxan. My question is what side-effects might I expect from this infusion. I am prone to severe headaches from IVIG, due partly to my inability to handle the viscosity of the liquid. I understand Rituxan is infused slowly the first time but more rapidly on the second, two-week-later infusion. Should I be super hydrating for these infusions in addition to the pre-medications prescribed? Other suggestions to minimize the side effects?

    Dr. Aggarwal:

    Some patients the immediate side-effect that can happen is infusion reaction while you are getting rituximab which can be managed by steroids. Other than that main long term side-effect is increased risk of infection. Which is the same side effect with steroids, methotrexate, imuran etc but possibility might be higher with rituximab. Otherwise rituximab usually do not cause headaches, GI side-effects, etc. Pre-medication could include benadryl, tylenol, steroid but is usually decided by your physician. There is nothing you need to do or take to prevent or minimize side-effects except seeing your doctor regularly, monitoring labs and if have any fever or infection then call your rheumatologist right away.

  • Realistic Expectations

    Participant:

    I will be starting Rituxan infusions soon and wonder what to realistically expect in the way of improvement. I realize every patient is different but statistically, how soon might I notice an increase in my strength? My CK is only about 350 (PM with IMNM) but in the last year have been getting steadily weaker. How soon do we decide that I need another round of infusions?

    Dr. Aggarwal:

    Generally we have seen that it takes upto 2-4 months for getting good effect of rituximab. You may need 2nd round generally after 6 months based on your symptoms. Sometimes patient only need one set of dose and not require recurrent infusion every 6 months, other patients require recurrent infusions.

  • B-cells

    Participant:

    Can you explain a bit about B-cells and how Rituxan combats them? Can two infusions really stop their action on my body?

    Dr. Aggarwal:

    B-cells are immune cells in your body. B-cells produce antibody and generally protect your body from infections. In myositis B cells become abnormal and start attacking your own muscle. So, thought behind rituximab is if you wipe out abnormal B cells then newer B cells that appear fresh are not abnormal. 2 infusions are generally enough to wipe out 99% of you B cell population in blood.

  • Additional Trials

    Participant:

    Do you anticipate any additional trials to help support the use of Rituxan for myositis patients?

    Dr. Aggarwal:

    I wish but there is nothing in pipeline for rituximab clinical trial. There are more studies being done on rituximab in myositis which will help us in treatment of myositis with rituximab but no trial is planned.

  • Insurance

    Participant:

    My physician believes I would benefit from this treatment but it is unclear if my insurance would pay for it. Do you have any suggestions on how to approach this?

    Dr. Aggarwal:

    This is very common problem. What we generally do is peer to peer with insurance company’s doctor or pharmacist. We send them the literature behind it and try to convince them. I have been successful 8 our 10 times but it really depends on your insurance.

  • Increased Risk of Infection

    Participant:

    I am concerned about the increased risk of infection that the drug company warns about. Could you elaborate on this?

    Dr. Aggarwal:

    Rituximab wipes out one type of immune cells called B cells. Our body have several types of immune cells including B cells, T cells, macrophages, neutrophils etc. So, definitly there is increased risk of infection on giving rituximab. But most patient tolerate it well and do well on it. Increased risk of infection doesn’t mean that you will get an infection. The percentage of patients getting serious infection is very low. Common infections are more common but those can easily be treated with simple antibiotic without much problem.

  • Specific Symptoms

    Participant:

    Are there any specific symptoms that Rituximab seems to alleviate?

    Dr. Aggarwal:

    NO. Mainly it help to improve muscle streght, rash and muscle enzyme.

  • Antibody Profile

    Participant:

    My physician wants to try me on Rituxan but I am not sure I want to start without any idea that it will benefit me. Is there a particular antibody profile that predicts a benefit from this drug?

    Dr. Aggarwal:

    Yes. Certain antibody profile has better outcome on rituximab than others. Generally, patients wtih some myositis associated antibody has more response than patients without any myositis antibody. Among the patients with myositis antibodies – anti-synthetase and anti-Mi2 and anti-SRP, TIF-1, have good response.

  • Advantages over IVIG

    Participant:

    What is the advantage of Rituximab over IVIG and what are the side effects?

    Dr. Aggarwal:

    Good questions. We don’t know clearly as there have been no studies to do that comparison. What we know that IVIG works well for dermatomyositis and some evidence for polymyositis. IVIG doesn’t have good outcome in terms of interstitial lung disease but has good outcome for dysphagia and severe skin rashes.For side-effect see on my answer to other question.

  • Success in Treating Resistant PM

    Participant:

    Good Afternoon,I have had PM for 6 years now, and take only IVig monthly. Prednisone had no affect so I stopped taking it about 1 1/2 years ago. I feel pretty good but do not have all my strength in my legs and my CPKs are still high (around 500). My doctor has suggested I try Rituxan, but I am afraid of the possible side effects.Can you tell me what side effects you have seen with this drug, how often they occur, and what success there has been in treating resistant PM.

    Dr. Aggarwal:

    If your strenght is not completely better then it might be a good idea to try rituximab. For side-effect of rituximab please read my response to other question. Mainly infusion reaction and increased risk of infection. These infusion reactions are generally mild and can be treated easily. Rarely you can get serious infection after rituximab but frequency of that is very low. Common infections like urinary tract infection, sinusitis, URI are more common but those can be easily diagnosed and treated by your rheumatologist/PCP.In our main clinical trial on rituximab in myositis about 85% of refractory patients improved on rituximab. Other studies have show about 50-80% response.

  • Flare Ups

    Participant:

    Hi. I have been receiving Rituxan since I participated in the study. I am certain that the rituxan works until it wears off at which time my ck will rise and I am in a flare. As long as I receive the riutxan before the year is up I can stay “flare free.” Does this sound right? Are there any labs that can be checked to keep an eye on this?

    Dr. Aggarwal:

    Yes. it does sound right and possible in some patients. Many patients need repeated doses of rituximab where as others may not need repeated doses of rituximab. CPK and aldolase are two labs that can be checked, however most of the time patient’s symptoms and physician muscle exam or skin exam are more important parameters.

  • FDA Approval

    Participant:

    Hi, I am no longer able to receive Rituxan due to the FDA not approving Rituxan for myositis. Why does it TRULY help so many people but was not approved and why would Genentech not help us?

    Dr. Aggarwal:

    Good question. See in the main clinical trial on rituximab in myositis, the study failed to show any difference in treatment early vs. treatment late. That is why FDA cannot approve the drug. So, I would say highiest level of scientific evidence is not in favor of rituximab. However, we still treat our patients with rituximab and many of them do improve. In rituximab in myositis study 80-85% achieved minimal improvement at least. Unless there is another definitive big trial on rituximab showing benefit it will be hard to get FDA approval.

  • Continual Use

    Participant:

    If Rituxan depletes B-Cells which works to keep inflammation down what is the risk of using rituxan continually?

    Dr. Aggarwal:

    Great question. We actually do not know for sure. We do have some evidence from other diseases. We know that from rheumatoid arthritis clinical trials in which rituximab was given the long term follow up suggested that several doses of rituximab are well tolerated without any major illness. However, we do not have very long term data to exactly answer your question.

  • Maximum Treatments

    Participant:

    PM since 05, 64yr, male currently on 5mgs of Prednisone per day & 2.5mgs of methotrexate per wk. Have had two treatments of Rituxan in 05 & 09 with good results. One treatment of IVIG in Jan 2014, resulting in severe rash over entire body. CPKs are currenly up to 1200 with increasing muscle weakness. My Dr. wants to do another Rituxan treatment. Is there any new Information on maximum treatments of Rituxan?

    Dr. Aggarwal:

    We don’t have good studies on multiple rituximab treatment in myositis patients. But we do have safety data from rheumatoid arthritis studies where patients were given multiple doses of rituximab and it appears to be safe and no major increase in infection rates on recurrent rituximab. Some patients need recurent rituximab every 6 months to 1 year to stay in remission. There is no right answer about maximal number of treatments of rituximab.

  • Timeframe

    Participant:

    How long should I know if Rituxan is working for me or not? I have DM and have had 4 infusions starting 5 weeks ago. So far I have not felt any positive effect.

    Dr. Aggarwal:

    About 2-4 months

  • Clinical Trial Participant

    Participant:

    I was in the clinical trial (out of NYC) 87% of us were helped by the retuxin. Why is it such a problem to be able to get it again ? And why was the trial considered a failure?

    Dr. Aggarwal:

    Because there was no difference in the group which got drug early vs. late. If the trial had shown that group that got rituximab early improved early as compared to one which got drug late then it would have been successful. But that didn’t happen and that is why despite 87% improving the trial is a failure. This is the reason FDA will not approve the drug and many patients are not able to get it.

  • Eligible Diseases

    Participant:

    Hello. I’m a member of TMA and a member of the Southwest FL Kit. My doctor has just prescribed Rituxan for my PM. My last Rituxan treatment was in Dec 2011 and it has kept the PM stable; however, after two and a half years, it’s now time for another boost as my CK numbers are slowly creeping back up. Due to the cost of this drug, I visited the website http://www.genentech-access.com/rituxan-nhl-cll/patients/find-patient-assistance/co-pay-cards and Genentech offers copay help. However, it’s only available for patients with RA, GPA, and MPA. Genentech’s copay assistance would lower my payment responsibility to $5.00 instead of the $2,000 I’ll have to pay. Is there anything TMA can do to help get PM and DM added to their list of eligible diseases? Also, is there anything I can do to help get PM and DM added to their eligibility list? Thank you for your help.

    Dr. Aggarwal:

    MA staff can answer this question but I doubt they can do much here. The drug is not on genentech assistance as it is not a FDA approved for myositis. The reason it is not FDA approved is due to the clinical trial failed. I wish you good luck with your treatment and assistance.

  • Getting Back to Full Strength

    Participant:

    I’ve just been diagnosed with DM with srp antibodies, my CK has gone from 6000 to 2500 and I ve been treated with IV methylpred followed by oral pred with no change in my symptoms. I’ve gone from being a normal 35 yo woman to being unable to stand or walk unaided. I’m due to start rituximab next week, when will I expect to see any improvement and will I ever get back to full strength?

    Dr. Aggarwal:

    It may take up to 2-4 months to see significant improvement. But I am glad you are taking rituximab.

  • Slow Infusion

    Participant:

    Having experienced side effects from too-fast IVIG infusion, I’m curious why Rituximab is infused slowly the first time and then twice as fast the second. Isn’t this risky?

    Dr. Aggarwal:

    If someone tolerate first infusion ok then the risk of any infusion reaction which 2nd infusion is very low. That is why 2nd infusion is given faster.

  • Muscle Weakness from Deconditioning

    Participant:

    I have junevile Dermatomyositis- had it since I was 6. I am now in my thirties. My lab work for CPK are in the normal ranges; however I am completly weak as evidence by physican muscle exam. The doctors think that I am weak due to deconditioning. We have tried Physical therapy, but it only causes pain and soreness in my muscle and then I am not able to do anything else for a few days because of weakness and fatigue. Would Rituximab be something that should be considered especially if the muscle weakness is b/c of deconditioning? Thanks

    Dr. Aggarwal:

    If your muscle weakness is entirely due to deconditioning or muscle atrophy then rituximab will not help you.

TMA:

TMA would like to extend a special thanks to Dr. Aggarwal 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.

Dr. Aggarwal:

Thanks for having me. I hope this was helpful for some patients.