MS Treatment Options: Part 3 - IV Infusions - Ben Thrower, MD - July 2016

[Music] thank you very much for for coming out and uh thank you to our sponsors for the evening have a neuroscience Genzyme a quart of pharmaceuticals am I missing somebody Mallinckrodt thank you guys for allowing us to be here this this evening so if you I see a lot of familiar faces this is part three of our MS therapies discussion we did the the oral therapies last month we did the injectable therapies and tonight we're gonna talk about some of the the drugs that are given by intravenous infusion or IV next month we're gonna do what's on the horizon or future therapies so hopefully you'll you'll join us do we have a date for that okay so twenty up 24 August 24th so same same bat-time same bat-channel 6:00 p.m. here August 24th and I'm going to see if my technology works here and it does so these are the currently available IV treatments for multiple sclerosis some of these are FDA approved some of them are off-label and we're gonna go through these in some detail so there's no vant Rhone or mitoxantrone Tysabri nate'll ism Abbe limb Trudeau alum to zoom AB rituximab and aqua lism AB we're gonna talk about those two together pulse solu-medrol or methylprednisolone and then we'll finish up with sigh toxin or cyclophosphamide are there any of these on there that that just raise your hand if you've heard of all of these treatments is everyone's so are there some you've never heard of before okay so we're going to start with my two zantron or no zantron no Van Tron was the first fda-approved infusible therapy and it wouldn't surprise me if some people here or in the audience on the internet have not heard of this drug and one of the reasons you may not have heard of it is we don't use it very much anymore it is a chemo therapeutic drug that's been around for quite a while but then when it was studied in multiple sclerosis it was shown to be effective in both relapsing remitting and in secondary progressive multiple sclerosis the way that we typically used this medication was given intravenously every three months sometimes we would use it in people who had very very aggressive relapsing forms of MS lots of active inflammation on the brain and lots of active relapses and in those people we might give it monthly for three months maybe six months one of the challenges with mitoxantrone is that there was a lifetime cap on how much you could get and if you were giving it at the three-month interval it ended up being about two years worth of the medication and then you didn't want to go any further and the reason you didn't want to go any further it was because there was risk of damaging the cardiac muscle so it wasn't damaging the blood vessels to the heart the drug can actually damage how hard your heart squeezes and can lead to congestive heart failure and the risk of that congestive heart failure got higher after about two years use of the medication at the typical dosing so the healthcare community the MS world was very aware of this cardiac risk so we would do echocardiogram where we look at how hard your heart squeezes in people on this drug in the original research there was a mention that the drug could also cause leukemia and it was felt to be about a 1 in 2,000 risk of leukemia as time went on and the drug was used more more often what we found and it was really our counterparts in Europe who first started seeing this it was discovered that that risk of leukemia was actually much much higher than one in 2000 maybe as high as 1 in 100 and it was a very aggressive form of leukemia acute myeloid leukemia which is frequently fatal we had two cases here at Shepherd Center the thing that was so scary about this leukemia is that it wasn't related to how long you had been on the drug you could get one dose of mitoxantrone and have risk of this leukemia so because of that leukemia risk you don't see this drug used much in the United States anymore some European country are still using it they feel like the risk might be worth it but very rare rare to see it used in the United States now Tysabri nettle is Ahmad this may be the IV treatment that most people are familiar with it's a once monthly IV infusion of 300 milligrams it's a type of drug called a monoclonal antibody you'll notice that a lot of the medicines on an original list nate'll is a map acryl is a map rituximab alum to the map the last three letters of all of these drugs is in a B that stands for monoclonal antibody now there are lots of these drugs out there they're used in multiple sclerosis there's some monoclonal antibodies they're used in other rheumatologic conditions like lupus and rheumatoid arthritis some of them are using certain cancers what Tysabri does is it binds to white certain white blood cells and it doesn't let them cross the blood-brain barrier to get into the central nervous system to cause inflammation in the first paper the first place it is probably one of our most effective drugs for relapsing forms of MS it's not proven in primary progressive or secondary progressive multiple sclerosis typically we think of Tysabri and someone who's maybe been on one of our our injectable therapies or an oral therapy and is either not tolerating the drug or their MS is breaking through in spite of that that baseline therapy and we go to this now as our second line choice it is it is possible to use it as our first line choice so if you have newly diagnosed MS and we think that the risk is worth it some people go on Tysabri as their first line treatment so why is it Tysabri used in everybody everywhere with multiple sclerosis progressive multifocal leukoencephalopathy PML PML is a brain infection caused by something called JC virus every now and then we have people get confused as there's another neurological condition out there called Jakob Creutzfeldt which also starts with a genesee totally unrelated to JC virus that's a bad disease caused by a weird thing called a prion jacoub Creutzfeldt sub is a bad actor people frequently or almost always die from that disease JC in relation to p.m. L stands for John Cunningham that was the first human who was ever described to where they found that the virus normally JC virus is a nothing kind of virus there are a lot of viruses out there that basically use us as transportation they use us to get from point A to point B and they really don't cause any any human illness that's what JC virus normally does JC virus lives in in the kidneys maybe in the bone marrow we think the way that it gets from one person to the next is actually you we pee it out so it gets out in urine so 55 percent of adults in the United States and in most countries carry JC virus and it's not a problem for them so we probably pick it up in childhood there's a lot of thought that if it gets out and urine maybe we pick it up in places like public swimming pools so if you're swimming in a public pool do not drink the water especially if you're in the kiddy pool so yeah hopefully you're not doing that anyway PML happens when your immune system is compromised and there's something about that normally benign nothing virus that changes it mutates and it becomes a very aggressive virus it leaves the places where it normally lives in the human body kidneys bone marrow and it goes to the brain and PML it can be very aggressive as of June 2016 there have been 667 cases of PML in people with multiple sclerosis on Tysabri that's in the whole world of those 667 people about 23% of them have died from it 77 percent of people have varying degrees of disability one of the areas of research is in those 77 percent of people who survive PML why do they survive what's different about their immune systems some of these people actually have almost no disability it's like nothing never happened to them some of those 77 percent of people are in nursing homes it's like they've have it have had a devastating stroke so there's a lot of research going on looking the antibodies and people who do well with PML trying to tap into that to see if it could it be something that would lead us to a treatment or a prevention or a vaccination for 4jc virus so your risk of PML if you're on Tysabri is determined by really three things the the whether you carry JC virus or not because you have to have the virus to get the the disease the length of time you've been on Tysabri and whether you've been on a prior immunosuppressant drug so things like mitoxantrone cyclophosphamide chemo therapeutic type drugs that suppress your immune system in the presence of the JC virus put people at a higher risk for developing this brain infection we've come a long ways in helping people determine whether they feel comfortable being on Tysabri or not one of the most important things has been developed is JC virus antibody testing we now have the ability to determine whether an individual carries JC virus or not are you in that 50% of adults who do or you and the 45% of people who don't the first generation blood test that we had simply said yes or no you have antibodies to the virus or you don't it didn't tell you how much antibody it was just a yes or a no what we're using now is second generation testing which is actually much better because it actually gives us a numeric value called the JC virus antibody index and what we can do with that number is we can put people into one of three groups either you're truly negative you have a number of an index number of less than point two your low positive meaning you're between point two and point nine or your high positive your greater than point nine and I'll show you a chart in a minute that we use actually to show people and say what is your risk if you were on Tysabri based upon those numbers I'll add a point here that I didn't put in the slides but doing the JC virus antibody index in a person on a drug like Tysabri is not something we do just one time it is possible for a person who doesn't have JC virus convert and develop one of these higher numbers and shift you from a low-risk group to a high-risk group the FDA recommends rechecking the JC virus antibody index every six months for people on Tysabri we like doing it every three months here just to be really obsessive and make sure those numbers aren't changing so if we look at the whole group of everybody with multiple sclerosis who's on Tysabri regardless of what their JC virus number is regardless of whether they've had a prior chemotherapy regardless of the length of time they're on treatment the overall risk of PML with Tysabri use is four point two two out of a thousand people when we start going through these numbers and talking about you know numbers per thousand one of the things I would really emphasize is that there's no absolute right or wrong we can't go to an individual and say you are the perfect candidate or you're the absolute worst candidate it's all about your individual risk tolerance I can get these same numbers to two very reasonable individuals with MS and one person could say absolutely not that risk is not okay for me and someone else would say I'm okay with that so you know what we want to make sure people understand what the numbers mean and then help make them a decision that's comfortable for them this I think is the most important table out there this takes that 4.22 per thousand number and says but there's a lot more information we can give people much more specific guidance this is from a researcher named Polina who published this a couple of years ago and what they did is looked at the JC virus antibody index number which was on that far left column so you can be less than 0.9 less than or equal to 0.9 you can be between point nine and 1.1 1.1 to 1.3 1.3 to 1.5 or greater than point one point five and then on the the top row we've got how long are you on treatment this chart only applies to people who've never had a chemo therapeutic drugs so if you've been on a medicine like a chemotherapy that's a that's a different risk group you are always going to be in a higher grupe if you've had prior chemotherapy but what you can see and where the second generation test is so helpful is that in that group of people that are technically positive they've got a number of greater than 0.2 but they're less than 0.9 so there with the old test we would have said you've got JC virus antibody in your system you're in a higher risk group what we know now is that there's a chunk with those people who have a positive test that when you look at that point 9 number or the point 2 to point 9 their risk is really no different from the people who have a negative number so these are these point one zero point three these are expressed in per thousand people so if you have a JC virus antibody number of less than 0.9 you have a risk of 0.1 Perth and one out of 10,000 people on Tysabri for the first two years as you go across to the next line 25 to 48 months your risk ticks up a little bit 3 per 10,000 then it goes up to four out of 10,000 and it stays there so if you if you're in that next risk group what if you're between 0.9 and 1.1 where your risk in the first two years is one out of 10,000 it goes to seven out of ten thousand and it stays there and so on so your highest risk group is down in that bottom right hand corner 8.5 for that equates to about one out of 120 people that's if you're number if you're JC Bars number is greater than 1.5 and you've been on treatment for more than four years your risk is up in the one out of 120 people group for me if I was making that decision for myself or if I was talking to a family member that's that's pretty high to me and I would we encourage our people who here at Sheppard who are in that group we're gonna start giving you a gentle nudge towards thinking about some other treatment do we have people who elect to stay on Tysabri even though they're there in that risk group we do these are typically people who've tried everything else out there and they feel really good on Tysabri and they feel like the risk is worth it so again there's no absolute right or wrong you hear a lot of things in the on the internet or read things saying that you can't use Tysabri for more than two years that's not true it's more than just the length of time is your JC virus antibody number and whether you've been on prior immuno immunosuppressants we're gonna shift now to our next IV treatment nestle entrada or alum to zoo map this is another one of those map drugs the the fancy immunologic term is that this is an anti cv 52 monoclonal antibody cv 52 receptors are present on the two major types of white blood cells in our body t-cells and b-cells so what this drug does is it knocks down the levels of both those types of cells it is a very very effective treatment for relapsing forms of MS not so much for progressive forms of MS it's it's given as a once a year IV dose the way that this works is you get five days in a row year one a year later you get three days in a row and then it's kind of on an as-needed basis if you're invested and it's not acting up you probably don't need to be retreated so there's a lot of watching and waiting after you receive this drug the safety issues with Lyn trata are something that we need to think about l'm trata is not something that we would consider as a first-line treatment it may not even be a second-line treatment because of the safety issues this is something where you really need to have the risk you know outweighed or outweighed by the benefits some of the side effects that we see with this drug are autoimmune disorders things like low platelet counts or thrombocytopenia a kidney disease called anti glomerular basement membrane disease and then thyroid problems the infusions themselves can be a little bit bumpy there are pre medications that we need to give when we give this medication some people look like they're sort of having a almost like an allergic type reaction when it's really a histamine reaction they can get red they feel a little short of breath they can be itchy one when they're getting their infusion there is an increased risk of certain cancers like mal Noma thyroid cancer and lymphoma the cause of those risks it is the is incredibly important that people not drop off the map there's safety monitoring that needs to be done meticulously with Lim trata we need to do blood testing blood count with differential looking at your kidney function looking at you at your urine test and that needs to be done very regularly and it needs to continue for four years after you receive your last dose of lung Trotta you need to get baseline and your skin exams because of the risk of skin cancers with this drug so this is one again that where the the the effectiveness is very high but the risk is also potentially significant and needs to - that's very important that we do regular safety monitoring with this drug I lumped these two drugs together rituximab and aqua ilysm AB because they're they're sort of in the same family these are both what we call anti cd20 monoclonal antibodies with the story with rituximab is that this is a drug that was originally originally designed to treat non-hodgkins lymphoma but it's not really a chemotherapy non-hodgkins lymphoma is B cells in the immune system growing out of control and so rather than using chemotherapy to treat that non-hodgkins lymphoma researchers found that during the lifespan of these B cells in the immune system there's a point in their life cycle when they have a receptor on the surface called a cd20 receptor it's almost like an on and off switch if you will and so that they could very selectively go in and turn off these cells that were growing out of control in these lymphoma patients and leave the rest of the immune system alone well that caught the attention of neurologists and rheumatologists because we know that b-cells play a role in multiple sclerosis they play a role in the cousin of multiple sclerosis neuro myelitis optica or Devex disease they play a role in lupus and rheumatoid arthritis so there was a research program looking at rituximab for multiple sclerosis researchers at the same time showed that rituximab is probably the most effective drug we have to treat neuroma whitus optica this cousin of multiple sclerosis none of our ms therapies have ever worked very well in neuroma myelitis Africa and nmo can be very aggressive people can die from it so rituximab was it was really a blessing for for those individuals as the research was going along in return for rituximab in multiple sclerosis one of the things that the research group wanted to try to improve upon was the molecule itself when you look at most of our map image it may be drugs you'll see that that before the MA B there's a zu natalizumab Tysabri lm22 zoom ab l'm Trotta rituximab was the only one of our map drugs that didn't have a zu in front of it and an X I in front of it and what that si means is that it's chimeric it's part mouse and mostly human that part Mouse part the antibody is what the research group wanted to get rid of because in theory if you have an antibody that is mostly human but a little bit mouse the human immune system could say you know what I don't like that Mouse antibody I'm gonna make antibodies to the antibody and make that drug less effective so that was the concern with rituximab so when the research group sort of humanized that and cleaned it up that's what our ilysm AB is once they change that molecule though it's set the research clock all over again so we were pretty far along in the research with rituximab when they changed the molecule that started the clock over again so aqua lism AB is the humanized version of this of this molecule it's slated to be FDA approved on December 28th of this year what's going to be very interesting is it should be approved for both relapsing remitting ms which is great news it will be the first drug ever approved for primary progressive MS so it should get approval for both of those forms of MS at the same time if so we have a lot of people on rituximab right now off-label we use it again for neural myelitis opteka we use it in certain situations with multiple sclerosis if those individuals on Rituxan if we switch them over to aqua ilysm ab and didn't tell them I would expect that they probably would never know the difference they're both every six month IV treatments what what would go an IV bag would obviously be different in the dosing of the the milligram dose is a little different with rituximab we typically use a thousand milligrams with the aqua ilysm ab we're gonna use six hundred milligrams one of the drawbacks with these drugs is they are very slow infusions they take about six hours to run in so twice a year someone's gonna be hanging out here most of the day back in the IV room and chatting with the IV nurses and and just hanging out for a bit we don't know yet but it's very possible when ocker ilysm app gets FDA approval there may be a warning label about PML progressive multifocal leukoencephalopathy and the backstory for why there could be is that with rituximab the very closely related drug there have been ten cases of PML but they were very distinct of nine of those ten cases were in the Rheumatology world for reasons we don't understand some rheumatologic conditions like lupus just the very nature of the disease itself we see a higher risk of PML in those individuals even without treatment when the rheumatologists use rituximab in rheumatologic conditions they almost always put it with a chemo therapeutic agent and Emmure an a methotrexate something like that so that that double hit on the immune system may be what's putting these people at some risk a small risk but still it's there of developing PML there has been one case of PML in the in the MS world that was an individual who was on Tysabri who had had high levels of JC virus antibody index and had been on the drug for quite a bit and was taken off for safety reasons got rituximab developed PML that really is a Tysabri PML case but because they had received a dose of rituximab it's gonna has to get labeled as a rituximab risk so there have been no cases of PML with with oralism ab we obviously will watch people closely and probably do some JC virus antibody index testing in my book and this is just me personally I don't think the individual who has JC virus antibody levels that are high is excluded from being on our Elizabeth we would still be comfortable and in fact we anticipate that maybe a group of people who are going to go on aqua lism ab fairly soon after it's approved are the individuals who are on Tysabri who do have high levels of JC virus and we're starting to get a little bit nervous and we're looking for another option shifting now to to pulse solu-medrol so or methylprednisolone so normally when we think of IV steroids solu-medrol methylprednisolone we think of it for relapse management so if you have an MS attack or relapse exacerbation you get three days five days in a row of IV steroids to treat that relapse and that is the traditional way that we use solu-medrol there is a some place in the in the toolbox for using pulse solu-medrol as your baseline therapy it's not done commonly I would say it was more common in a few years ago when we didn't have as many treatment options sometimes it was something that was added to a baseline treatment for instance if you were on Avonex Copaxone Betaseron and you were having some breakthrough ms activity maybe we would add the pulse solu-medrol to that there are a lot of different recipes out there for how solu-medrol can be given and pulse therapy some people would do one day a month IV others would do what we call a three one one protocol where you would do three days in a row month one one day month two one day month three and then start that cycle over again steroids over the long term we have to be aware of the of the long term risks of steroid usage it can raise your blood pressure can raise your blood sugar you can see mood changes some people are very happy and energetic and motivated and euphoric on steroids some people are evil and mean and their families want to move out when they're on steroids some people don't sleep at all and you just never know in a given individual how they're gonna respond potassium levels can drop weight can go up bone density can go down so that we have to be aware of some of these other things one of the most significant side-effects that we sometimes see with steroid usage is called aseptic necrosis of the femoral head so the the ball of your femur where it sits in the hip joint in some people the blood supply is is somehow affected by the steroid usage so that bone gets very crumbly and brittle and you can actually have that ball of the hip joint just pop off and in people and which is obviously not a good thing to have happen and then lastly premature cataracts are something that we see with with steroids I'm gonna finish up before I turn it over to you guys for for questions with cyclophosphamide or sight ox an old-school chemo therapeutic drug it's used sometimes in the MS world sometimes the the rheumatologist used this for things like lupus and rheumatoid arthritis usually is given as a once a month IV dose somewhere between 500 milligrams and a thousand milligrams some of the universities like Harvard do it'll do things a little differently they will do what I call induction therapy so if you have aggressive newly diagnosed MS they will use high high doses of cyclophosphamide for a very short period of time to really get in and whack your immune system hard kind of hit the reset button to get things restarted again and then so the risk is a little bit higher doing it that way but they are still doing studies with that when we think about cyclophosphamide or cytoxan safety can cause nausea we usually get premedicate people with something for nausea hair thinning unusual we have to monitor your platelets they can get low you can have increased risk of bruising or bleeding any time we alter the immune system significantly there could be a risk of secondary cancers down the line and then hemorrhagic cystitis or this irritation of the lining of the bladder or you start having some bleeding into the bladder as is a is a risk with cytoxan we don't use a lot of this drug anymore we have so many other options out there you know when we think about drugs that are like mitoxantrone or cyclophosphamide that are more chemo therapeutic I always think of those are sort of more the sledgehammer approach you know rather than manipulating one small part of your immune system like you might monoclonal antibody this is more just whacking the playing whack-a-mole with your immune system and kind of clubbing ended into submission which is not our favorite thing to do before I turn it over to QA I'll finish up so this is other than MS is a passion this is something that our family's passionate about I think we've talked about this a little bit before it's near and dear to our heart we just got back from Nicaragua on Sunday so we do our twice yearly medical trips down there the on the top left is our 18 year old he is he's a gentle giant the kids down there love him so that's him torturing one of the small children down there the he's like a Pied Piper he always has tons of the children from the village around my wife's there in the middle that's one of the houses we were going out to to do a home visit bottom left this is not an unusual sight in Nicaragua this is a typical house in the village they're literally think of the fort's if you're a guy think of the forts they used to build in the woods when you were a kid you get some plywood or some lumber and you still a piece of metal from over here that's what a lot of people live in down there dirt floors no running water no electricity one of the things that is amazing to me in this in the village is the mud eighty-five percent of the population is Catholic and there is a little cat small Catholic school in the village the boys and girls wear uniforms so white shirts slacks for the boys skirts for the girls perfectly pressed perfectly cleaned there's not a washer or dryer in this entire village of 2,000 people everything is is washboard or scrubbed on a stone and then hung out to dry but you'll never see a stain underneath these shirts how they keep their the uniforms so clean is just mysterious to me they're very proud about it the gentleman in the middle there in the wheelchair is is that's Armando he is a 45 year old gentleman who had a spinal cord tumor so he's paraplegic this guy so most of the people there their income is from subsistence farming coffee beans things like that this guy who is you know has a very very difficult time has put four of his five children through college just amazing they're mostly have gone into the veterinary field his fifth child is in grade school right now but will probably go to college like they like the four siblings did so just a real testament to how tough the people can be and then the two pictures of the the geography that's a volcanic crater lake up on the top and the dark is actually a lava field and then on the bottom corner that is Messiah that's one of the many many many volcanoes and in Nicaragua that one is is active and and that's actually looking from the window in the airport it's it's that close to the to the airport yep thank you guys very much I will let case you wrap it up here and and with some last thoughts I appreciate you coming out be careful going home

Channel: Multiple Sclerosis Foundation

Views: 4,114

Rating: 4.9024391 out of 5

Keywords: MSFocus, MS, Multiple Sclerosis, Ben Thrower, Treatment, Infusions

Id: Rrbs6k023vg

Length: 31min 54sec (1914 seconds)

Published: Thu Nov 17 2016