Add Methotrexate??

[Mehita]

DS had a follow up routine GI appt today and I have a couple of questions for you all.

First thing to note, he's lost just shy of 4 pounds over the last two months. No explanation. GI hmmm'd about it, but wasn't overly alarmed. Scopes (routine) are scheduled for March 16th.

Background to my question: DS was on 5mg/kg every 8 weeks in April of 2015 and was having minor symptoms so we tested his Remi levels back then. He had 0 Remi in him and 24.4 antibodies. As a result of those results, he was bumped up to 7.5mg/kg every six weeks and has been doing fine. The GI ran Remi levels again at his last infusion on Feb 18th and the serum level came back at 8.4 (they want to see it between 5-10) so that was good and his antibody level dropped from the 24.4 to 7.8, which is good too. Isn't that odd though? I guess I've never heard of antibodies dropping.

His GI said he'd like us to consider adding Azathioprine (which he's been on before as a mono therapy), 6MP or methotrexate to help keep the antibodies in check and prolong use of Remicade. I get and understand all that, even agree, but what I'm confused on is why now? Why didn't we do this back when the antibody levels were high? If his scopes come back clean, would you still add something?

DS says he wants to add something. He listened to the whole discussion on how this may be better for the long term, etc. So now the question is which one. When he was on Aza, he had no side effects, but it wasn't effective either. He has an intermediate TPMT and would be on a lower dose because of this, but if he's on a lower dose, does it still have the same affect in preventing antibodies?

Can someone explain exactly how adding one of the three benefits the Remi? Is one better than the other?

His GI also says he'd like to get him to every 8 week again eventually. Having been in this group for so long, it seems like most of our kids are 6-7 weeks. I mentioned that to him and he said there is no difference between adults and kids. But if 6 weeks is working, why change it?

Thanks

 

[Maya142]

I'm not sure why he would add MTX or Imuran now except to prevent your son from building antibodies in the future. Hopefully someone who knows and understands more about antibodies can answer that!

I can tell you that Imuran/6MP risks scare us more than MTX risks. However, my younger daughter cannot tolerate MTX and so is on Imuran. With MTX, she had bad nausea, dizziness and fatigue and was so miserable she was in bed for two days every week. It just wasn't worth it, even though it worked very well for her joints. We tried many things - switching from pills to shots, lowering the dose, upping her folic acid, Leucovorin (folinic acid), several nausea medications - but nothing helped enough.

The higher skin cancer risks of Imuran especially scare me but we don't have much of a choice. If she could tolerate MTX we would definitely try that. With Imuran, she has only had nausea when increasing the dose - no other side effects. Her blood work looks good. The advanatge of 6MP/Imuran is that you can check levels - last time she was on Imuran, we were surprised to find that she needed quite a high dose for her weight, so that her levels were in the therapeutic range.

Every kid is different though - MOST kids have no issues with MTX, or if they have side effects, they are easily controlled with Zofran. My older daughter has been on MTX for years with no issues. She is on Humira too. In her case, the MTX is to help her joints, but also to prevent antibodies. Her rheumatologist likes to keep patients on both an immunomodulator and anti-TNF, especially with Remicade but also with other anti-TNFs, particularly in patients who have already been on multiple anti-TNFs.

The MTX shot has a very small needle and is not too bad. Both my girls said it doesn't really hurt, besides the poke. The medication itself does not burn like Humira. Both girls gave it to themselves. They sometimes used ice or Buzzy but neither really needed it because they weren't bothered by the shot. We used to give the shot in the evening, on a Friday or Saturday so that they had a chance to rest the next day.

We never got to 8 weeks (both my girls needed Remicade at 4-5 weeks) so I can't answer that. Some GIs are conservative though and if he can manage on 8 weeks, I guess that would be the goal.

There are some good presentations on Youtube about the use of Thiopurines in Pediatric IBD:

https://www.youtube.com/watch?v=ayQxJJ603Vw

https://www.youtube.com/watch?v=ayQxJJ603Vw

Good luck!

 

[CrohnsKidMom]

I don't know why the GI would pick now to add Asa/MTX either. My best guess would be that maybe when the antibodies were high he thought your son wouldn't end up being on Remi for the long term, but now that the antibodies are low he should add something before they go up again?! I really don't know!

My son was on MTX injections as a monotherapy and had a lot of nausea associated with it. It would start immediately after the injection and wear off by lunchtime the following day. It made him dread Friday nights. When he started Remi, he was changed to a lower, oral dose of MTX and he has no side effects from that at all. I give him some anti-nausea med with the MTX however, just in case.

Also, if at all possible, our GI avoids giving imuran/6mp to boys.

My son is on an 8 week Remi schedule, but had his trough levels tested to ensure the med was at a therapeutic level just prior to the next infusion.

 

[my little penguin]

You add Mtx /6-mp /Aza etc to reduce the body from fight against the med more .
This allows the remicade to be more effective because it can do what is suppose to do and not waste remicade on just fighting the immune system.
The immunosupresants will cause the levels of remicade to increase in his blood without actually giving more remicade.
Typically the dose of immunosuppressants is very small when given in combo with a biologic since it just is there to boost the biologic not do the heavy hitting.
The scope in March wouldn't really have any baring on the use of immunosuppressants to maintain his antibody level . That is the goal to not reduce but rather at minimum maintain where he is at which is very low.
They know the higher levels of remicade in the system the lower the risk of antibodies forming in the first place .
So immunosuppressants boost the remicade levels a lot.

Ds got very nauseous with injectable Mtx as a monotherapy
But has had no issues with oral Mtx combined with humira.
He does take folate at 2 mg a day which allows him to not have side effects
Not found of skin cancer issues with 6-mp or Aza

Good luck

 

[pdx]

I don't have any real advice for you, but I just wanted to say that it's great that your son's antibodies levels have dropped and that he's been able to continue on Remicade. I'm so glad that the increased infusion frequency helped.

 

[crohnsinct]

We added mtx a year into O's treatment. I think the GI is thinking he dodged the antibody bullet mine as well protect him the best way possible now. Personally, I would add it. I have read it is only a matter of time before antibodies start forming. So my thinking would be that he could still build antibodies. I know some GI's discontinue the use of immunomodulators after 6 months etc but I think most ped GI's are in the continue camp.

Methotrexate has been shown in studies to be just as effective as azatioprime to prevent antibodies.

 

[crohnsinct]

PS...the longer the kids are in remission and with good levels our doc does try to get the kids moved out to 8 weeks and lower doses of Remicade.

O was at every5 and 12mg/kg for a while and 4 years later she is every 7 weeks and 5mg/kg. A healed bowel doesn't sop up the medicine the way it did when inflamed...Also, with inflammation present a fair amount of the drug is lost in the poop. So higher levels are need with inflammation but as healing occurs yo can move interval out and/or de escalate dose

I think the reason most around here are at 5-7 weeks is because all the healthy, healed happy 8 weekers are off enjoying their lives. The forum naturally is going to have more of the population that is having issues etc. Therefore more frequent infusions, higher doses. etc.

 

[Tesscorm]

Mehita, I don't have any advice for you... but hope results come out well in scope results!

But, I do have some questions re remi...

The immunosupresants will cause the levels of remicade to increase in his blood without actually giving more remicade.

They know the higher levels of remicade in the system the lower the risk of antibodies forming in the first place .
So immunosuppressants boost the remicade levels a lot.

If the goal is to keep a higher level of remi, why not increase remi rather than introduce another med? Assuming you are not at the max, why wouldn't increased dose or frequency be the better option over adding an immunosuppressant?

I have read it is only a matter of time before antibodies start forming.

the longer the kids are in remission and with good levels our doc does try to get the kids moved out to 8 weeks and lower doses of Remicade.

Isn't this contradictory? Considering that levels testing is not done frequently (ie would be different if was part of regular labwork), isn't it a risk to lower frequency/dosage?

S has his next follow-up Monday and I was thinking of asking for a levels test and about moving him out to 8 weeks (he's at 6 now).

And, one more... how often do your kids have levels tested?

Mehita, I hope I'm not hijacking your thread and that this info is relevant to you too!

 

[my little penguin]

Increasing the remicade by itself is not as effective since the body is still fighting against it
The Mtx stops the body from fighting and allows the remicade to be more effective

 

[Mehita]

Mehita, I hope I'm not hijacking your thread and that this info is relevant to you too!

No worries, Tesscorm! You're asking all of my follow up questions.

I think we're leaning towards oral methotrexate. Is the pill once a week also? And what is the purpose of the folate? To prevent nausea?

No ideas on why antibodies would drop? Again, I wish I could think quicker on my feet. I was so happy to see the numbers, I didn't think to ask at the time. I should just set up two appts. One for fifteen minutes after the first ends and I've had time to process and think!

 

[Clash]

The pill for is taken once weekly just like the injection.Methotrrxate is an anti-folate so it's important to supplement.

 

[Mehita]

Increasing the remicade by itself is not as effective since the body is still fighting against it
The Mtx stops the body from fighting and allows the remicade to be more effective

So, theoretically, adding methotrexate could allow him to lower his dose or stretch out to eight weeks again at some (good) point in the future.

What is the typical methotrexate dose?

 

[Maya142]

Methotrexate dose varies. My kids have been on anything from 7.5 mg to 25 mg. The higher doses are often given by injection. Sometimes kids with Crohn's are given the injections because the pills are hard for inflamed intestines to absorb. So it really depends on your GI.

While on Remicade, usually lower doses are given. Anywhere from 7.5-15mg I'd guess (which is 0.3 - 0.6 mL if given by injection).

Folic acid is important and I'd also get a prescription for Zofran if you don't already have it, just in case. Folic acid can help prevent a lot of the side effects including mouth sores and hair loss. My daughter takes 2 mg daily but we started out at 1 mg daily. When she started having mouth sores, we increased the dose.

When my girls were first put on MTX we had to do weekly then biweekly blood work for a while to make sure it didn't impact their livers.

Good luck!

 

[pdx]

My daughter takes 15mg of MTX orally each week. She takes 1 mg of folic acid daily, but I've heard of others taking a larger dose weekly. She takes zofran at 8pm on Saturday, and then the MTX at 10pm just before falling asleep, and she wakes up Sunday feeling fine.

Tesscorm--our doctor has checked Remicade levels twice so far, once after 3 months on Remicade, and the second time after 5 months. Both were due to my daughter still having symptoms, and both times the levels suggested that an increased dose was needed. The doctor suggested testing levels again this spring; I'm assuming that this one is to see if we can decrease the dose or frequency.

 

[Jmrogers4]

Even though Jack is on remicade as a mono therapy it's only because he doesn't tolerate methotrexate and his GI is adverse to giving Imuran/6MP to boys if there is another option.
His GI only seems to test levels if something's off, we tested Jack's when he started to lose weight but since they all came back good, he's thinking that maybe those levels aren't right for Jack and since we had good results at 10ml/kg every 6 weeks before we moved to every 8 weeks he wanted to try every 7 weeks but insurance denied that (still fighting that battle). I kind of wish we would have been able to add metho and keep him at every 8 weeks.
He took oral metho once a week didn't have problems with nausea that we noticed but then he took it Friday night before bed, it actually seemed really effective against his crohn's

 

[CrohnsKidMom]

Tess, my son started Remi in Jul 2015 and had his Remi levels checked at the Oct 2015 visit (just prior to the infusion). His levels were good, so they likely won't be checked again unless there's suspicion the levels have dropped. Our GI said they just recently started testing levels in all their patients, whereas before they would just do it if they had real cause to.

Note: My son will likely have an increase in his Remi dose next time due to his weight gain. I was told the MTX dose would remain the same for now as its purpose is just to prevent antibodies.

 

[my little penguin]

Crohnskidmom
Remicade is always done by weight
It's given by mg/kg so the amount of the 100 ml
Bottle given in the Iv changes by how much the kid weighs but the dosage is still
5 mg/kg or 7.5 mg /kg or 10 mg/kg
So the dosage stays the same

 

[CrohnsKidMom]

Thanks for the clarification MLP. My son is given 5ml/kg, so yes, I guess the dose is the same, it's the amount given that is increasing.

 

[Worried mama]

My son has been on remicade for over a year and we are introducing mtx on March 11th, going to hospital for training on how to give injection. Our GI prescribed injection and did not offer us the pill option. He will be taking 15mg a week. He also prescribed a 20mg capsule of folic acid. He said to wait on the zofran to see if it's needed, he said many kids don't need it and he's got enough going into his body as is. Praying he tolerates the mtx well. We are adding mtx (and tube feeding at night) to help try to get inflammation under control, scopes still showed significant inflammation. Tube is so he gains some weight.

 

[my little penguin]

I would ask about the folic acid
I have never heard of taking 20 mg
Ds takes 2 mg total a day (1 mg in the morning and 1 in the evening )
The Rheumo thought that was high .
He takes folate instead of folic acid since he absorbs it better

 

[Worried mama]

I would ask about the folic acid
I have never heard of taking 20 mg
Ds takes 2 mg total a day (1 mg in the morning and 1 in the evening )
The Rheumo thought that was high .
He takes folate instead of folic acid since he absorbs it better

Ahh, you are right, it's 1mg folic acid tablet a day. I was reading label from something else....

 

[my little penguin]

If folic acid doesn't work ask for folate
Easier and Ds got ride of side effects of Mtx that way

 

[Maya142]

My kiddos both took 2 mg of folic acid. We tried 1 mg first, but they both got mouth sores so their rheumatologist increased their doses and that helped a lot. My older daughter still takes 2 mg of folic acid daily.

 

[Jenn]

I think doctors are currently advised to use combo therapy. I got some research reports from mine and my conclusion is that though combo helps to induce remission and can also prevent antibody development, it's unclear whether it's necessary to maintain it and for how long the combo should be done for. The results were mixed. I agree with using MTX vs 6mp/aza for the young male lymphoma risk. For some reason, I was hesitant to start mtx for my son when his GI pushed last year. There's no telling the future and I might kick myself later, but we've been holding off adding mtx to his Humira right now as the monotherapy is working for him. (I should point out that we did do a year of combo therapy with 6mp but stopped, didn't want to do another combo for seemingly no reason and no end date)

 

[Mehita]

Thanks for all the input, everyone. I'm 99% sure we'll go the mtx oral route after scopes. Only waiting until then (two weeks) because that's when we'll see his GI in person next and it will be spring break so no missing school if he does have side effects.

Is folic acid a prescription or OTC?

Also, a friend who's daughter had been on mtx (different disease and dose) said to ask y'all if there is a sterility risk at this low dose. Her daughter was on a much higher dose and was told having kids in the future may be questionable. Does anyone know anything?

 

[Maya142]

We were told that our girls would be able to have children - they'd just have to be off MTX for a while before they got pregnant.

Some GIs and rheumatologists insist that teenage girls have to be on birth control while on MTX but that is because if they get pregnant while on MTX, the baby could have birth defects.

The doses used for Crohn's and arthritis are tiny compared to the ones used for cancer.

The other thing to tell your son (since he's a teenager) is you are not supposed to drink on MTX. That said, my older daughter is 22 and definitely drinks on it. Her rheumatologist is aware and says an occasional drink is ok. Her blood work has been fine, so far.

Our folic acid is prescribed, but I think you can get it OTC.

 

[Maya142]

http://qjmed.oxfordjournals.org/content/92/10/551

MTX demonstrates significant teratogenicity. Skull and limb abnormalities are most frequent. The effects are unpredictable, making counselling difficult in individual cases. Depending on the condition being treated and the age of the mother the risk of abnormality and its consequences may be seen as acceptable.

Women wishing to continue with a pregnancy following exposure to MTX in the first trimester can be informed that there is a 10/42 chance of abnormality in the fetus on the basis of data from cases of MTX exposure. Four out of 13 cases of low-dose (<20 mg/week) exposure have resulted in abnormal fetuses. This incidence of abnormality is at least twice that seen following anti-convulsant exposure, where women are given an overall risk of malformation of around 10%.

In cases of MTX exposure, the drug should be stopped and women wishing to continue the pregnancy should, following counselling, be offered treatment with folinic acid for at least 5 months in order to minimize MTX effects on the fetus.

Women should be warned that there may be a small increased risk of spontaneous abortion early in pregnancy, and advised against taking MTX if they are considering conception. Those who choose to stop MTX and proceed to pregnancy should be advised against conception within 6 months of taking MTX. In the event of conception within this time, full counselling and close fetal monitoring should be offered.

MTX treatment is unlikely to have a major effect on short- or long-term fertility in men and women, but a washout period of 6 months cessation of treatment prior to conception is advisable to prevent the small chance of chromosomal abnormalities in offspring.

Breast feeding in mothers taking MTX will lead to infant MTX exposure and should be avoided.

With the increasing use of MTX in the rheumatic diseases and other inflammatory conditions, it is essential that all cases of MTX exposure in pregnancy are reported to central surveillance bodies to provide a complete picture of the teratogenicity of MTX. In the UK, this is the National Teratology Information Service, which also now monitors CSM reporting. Exposed children and their offspring should be monitored closely in the long term for the development of delayed neoplasms or second-generation congenital defects.

 

[crohnsinct]

Second maya's post. It isn't that they can't get pregnant but that they shouldn't due to the risk of birth defects..this goes for both male and female users.

Also, second and third the risk of injury to the liver if you drink while on Mtx...I have told my girls their livers will blow up if they so much as a sip...I will pay for the therapy later...jk of course

 

[awmom]

Hi Mehita, sorry for the late post. N has been on remicade for bout 5 years and he was just started on Mtx about 6 months ago. His pedi GI didn't seem to think it was necessary even though when we took him to Boston Childrens for a second opinion regarding his surgery the GI there said he should do a combo. He has a new GI as of 6 months ago and he wanted him on Mtx/folate to prolong the effectiveness of the remi. N takes 5mg/Kg of remi at 8 week intervals. He used to be at 10 week intervals which always worried me, but they had done that because his WBC was getting too low.

I never thought I would be relieved to have my boy on yet another drug, but somehow I am, hoping he can remain on the remi. He is taking Mtx in pill form and luckily did not have any side effects. The folate is OTC but he had the pharmacist recommend which one to get. My biggest worry is the drinking and his liver. I can only hope he is moderate.

I hope DS's colonoscopy comes with only good news!!

 

[Mehita]

A benefit(?) of Celiac is that most alcohol contains gluten and GF beer is pretty expensive. He's so picky though and can't even stand the fizziness of pop (soda) that I don't see him drinking beer for a long, long time - or at least not while he's on my watch.

Thanks for all the input!