Guide to MTX according to Lamb's experience

This isn’t medical advice BUT my experience with what has proven to be one of my favorite meds.

  • IF you are taking it in pill form bad things are more likley to happen as it goes through the GI system. That is the cause of almost all the side effects reported.

  • The side effects most commonly reported on the “internet” are for a dose nearly 100 times greater, but are adopted by arthritis patients for reasons I don’t know. Its darned easy to talk yourself into them when they would not occur if you were “less” informed. The dose is no where near being “chemo therapy”

  • Injection is the way to go. Not only will you require less of the med to be effective with an equivlent pill dose it is more effective and better absorbed/used by the body

  • For the least shock/effect to the system inject in the fattest part of your body with a 3/4 inch insulin syringe (usually wthin 6 inches of the navel) If needle don’t bother you I prefer an IM injection with at least a 1’ needle.

  • Water Water Water… If your pee has ANY color to it when you inject, you will have more side effects than if you are water logged continue to drink water the day of and and day after injection to the point your pee looks like water. (in fact if its this way every day all your meds work better and YOU feel better.

  • Despite what would SEEM to be logical inject early in the week IN THE MORNING before your most active times and keep up your activity. You likley won’t even notice whats going on if you are busy. If you take it before your reat/down time, you WILL lose that time to the med. You need that time for YOU. Motion is lotion, activity following MTX is treatment. If you lay around waiting for something BAD to happen, it will.

  • Of course you take your folic acid but the more you take, the more MTX you need to be effective

  • The best combo I have found is no Folic acid in the evening before injection, none the day of or the morning following.

  • Let me repeat INJECTION and LOTS of fluid. avaoid caffeine and NSAIDs the day of and morning following taking the med. If you MUST drink even MORE water.

  • PLEASE don’t fear this med. It is NOT replaced by biologics. Use will lower peripheral pain which the bios don’t touch and dramatically increase the life span of many/most biologics. Remember changing biologics always involves a gap. WE DON"T WANT a gap.


I’m doing well on Enbrel without Methotrexate, but when you say it will increase the span of a biologic, that worries me. I really don’t want to add more meds to my list of 7 plus Enbrel…I take several meds for my heart and a cholesterol lowering med.
Should I be concerned that Enbrel is going to “poop out” on me faster because I don’t take MTX?

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Enbrel is not one of the bios that MTX clearly extends the life of. Here is an excellent study of dual therapy vs. monotherapy. Humira is the one where it makes the biggest difference although it does effect all including Enbrel. Extension of bio’s life isn’t the ONLT indication for MTX (now should it be. Mostly its an added benfit although necessary with at least one BIO (remicade)


So, it’s not proven that MTX extends the life of Enbrel? - but ?
I tried to read the study but my eyes give me trouble when I read for too long.
Can you explain that to us—those of us who take Enbrel without MTX? Enbrel has been effective for me for almost 4 years now. It has affected my WBCs in that I have a lower count and sometimes leukopenia. I would think MTX would lower my WBCs even more, putting me at greater risk for infections and other problems.
I’m just wondering why the difference in effectiveness of MTX with other biologics vs Enbrel.

Probably not you surpressing the same portion of the system with either med. Once it’s done it’s done.

Enbrel doesn’t create antibodies for most because it is human dna ( granted it’s grown in Chinese hamsters) humira is synthetic dna which can cause the body to create antibodies. Remicade is animal dna which does create antibodies.

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You mean protein or antibodies instead of DNA right?

I’m guessing this is what you meant:

"The next step is changing the cells to make the appropriate antibody. In some cases, that means injecting the cells with the antibody target, and letting it make antibodies naturally. More likely, it involves further genetic engineering. Extra DNA is introduced to the cell, to try to get it to make the correct antibody. Because non-human cells make non-human antibodies (which the human immune system recognizes as foreign), those cell lines have to be designed to make partly or fully human antibodies.

Partly human antibodies are usually called ‘chimeric’ antibodies. Remicade (infliximab) is a chimeric antibody, made from mouse cells that have been engineered to make human-like antibodies. The resulting antibody is about 30% murine (mouse) and 70% human. The murine part is why people develop allergic reactions to Remicade.

A lot like a mouse, really.
Cricetulus griseus, the Chinese hamster
Humira (adalimumab) is a fully human antibody, but it is made using Chinese hamster cells. In this case the researchers have been able to design a genetic sequence that makes a fully human antibody, without using any DNA from the hamster cell itself in the sequence. Because the product of that process looks like a regular human antibody, reactions to Humira are less common. The key point here is that even ‘fully human’ antibodies can be made by not-fully-human cells."

Nope I mean DNA, . Biologics are made from recombinant DNA. an Important process for producing biologics, requires isolating the DNA from human cells and potentially modifying that DNA segment, inserting it into bacteria or a mammalian cell, and getting that organism or cell to express it. The insertion process has a great deal to do with whether or not antibodies will be produced. Something (DNA) gets the body to produce the proteins. If the immune sytem senses something doesn’t belong it starts the process of creating antibodies. Granted I have over simplified it. Once you have isolated the DNA all kinds of things can happen. On the project I worked on we developed and MPL adjuvant which has lead to a step beyond biologics and gone into “vaccines” MPL adjuvant is only produced one place in the world (Hamilton Montana by GlaxoSmithKline who bought the company i worked fo Ribiimmunochem. The adjuvants have done amazing things including cancer treatment and the hepatitis vaccines. But by far and large the biggest effect has been immunotherapy for cancer. Over the next few years that therapy will be applied to many diseases. In fact my old group just announced human testing for would you believe THE HUMAN COLD. These aren’t immunizations like the measle shot but rather disease fighting. The adjuvants have had and amazing effect evereywhere including most recently Ebola. But they are all DNA based and something that causes other things to happen, so you are right about proteins that attache to IL7, TNF etc but its all in the DNA For example a Chimeric Antibody, change any species to any other IgG isotype but really is a modification of DNA.

The basis for all of it is Recombinant DNA technology, which is the joining together of DNA molecules from two different species that are inserted into a host organism to produce new genetic combinations. Recombinant DNA technology is what produces the “eternal cells” that allow manufacture of biologics

You’re not injecting DNA… The drug is made using DNA but you’re injecting proteins…

Sort of. Before double stranded DNA is turned into a protein it first goes through a process called transcription to turn DNA into single stranded RNA RNA is an important link between DNA and protein because RNA codons
give the code for the building blocks of protein. These building blocks are called Amino Acids
. There are 20 amino acids and they form chains called polypeptides.
RNA codons are read by your biological machinery and turned into polypeptides through a process called translation.

The amino acid codes that are determined during translation are extremely important because the structure of a protein ultimately depends on its amino acid sequence.

The reason myosin proteins and antibody proteins that recognize foreign invaders look so differently is because they have different amino acid sequences that determine the structural properties of each protein which goes back to the DNA. Most simply put for biologics, “the product is the process.” Because the finished product cannot be fully characterized in the laboratory, manufacturers must ensure product consistency, quality, and purity by ensuring that the manufacturing process remains substantially the same over time.

That’s a lot of big words… but it’s still saying the same thing… the antibodies produced need to be compatible with all humans… you need the right DNA inside a cell to produce those proteins… but that’s like saying you’re eating a recipe instead of saying your eating the meal…

There are proteins in your body that would cause my body to make antibodies… there’s even proteins inside my body that would cause my body to make antibodies if they ever come into contact with my immune system… that has nothing to do with the DNA being synthetic or inside a mouse…

Of course the process is important and needs to be good… but you’re still not injecting DNA…

You are eating the ingredients of that recipie. In the case of bioloigics the DNA is like a building block of the foundation. A foundation built with styrofoam blocks will be different than one built with the blocks made of concrete. In the case of the “arthritis” biologics it makes a hug e difference whether th foundation DNA is fully human, synthetic or modified mouse DNA. The DNA is very much a part of the final product and RNA production that builds the protein after injection is dependent on the DNA present. It also defines the difference between whether it is an MAB or PAB. Biologics are all MABs which is a function of the DNA. Irregardless wheter you consider the DNA OR the proteins the boddy"s immune system recognizes the difference in the DNA and acts accordingly. Thus you have more antibody production with Remicade, a bit less with Humira and even less with Enbrel. That is all a function of the DNA which the immune system recognizes as it is a part of the medication which also determine the protein production. The protein produced is the active part of the medication, but the nature of the protein is totally dependent on the DNA present. The antibodies incidentally are NOT compatible with all humans thus site reactions and an occasional allergic reaction. That also varies with the DNA. Remicade has the most reactions (a big reason it is infused along with benedryl or similar) and Enbrel the fewest and Humira somewhere in the middle.

Heres a pretty good picture of protein I used to use when explaining the process (I’m sure you remember the nucleaus of protein is primarily DNA which allows the protein to replicate:


These two statements contradict each other…so, is it Enbrel or is it Humira that’s human DNA?

Enbrel has recumbinant human DNA which is basically just cloned. The first step in the process requires a cloning vector which in the case of Enbrel is in the uterus of of Chinese hampsters. Humira is human in that the DNA involved was created in test a tube by process called phage. When it produced using hamster cells as growth media the process is glycosylation - the addition of sugar residues by the host organism during manufacturing process, is a major post-translational protein modification resulting in different structural isoforms or in this case whether you get humira. Or something else. BTW glycosylation is not unusual in making biologics. Keep in mind enbrel is not a monoclonal anybody because of the process and DNA, so because of the variation is it less likely to spur Antibody production against it, it messes less with the immune system and according to this study Less likely to result in infections etc. And I just realized I made one of my typical typos which is likely the source of confusion “Humira is synthetic DNA” should say "Humira has synthetic DNA.

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Wow, so over my head. Basically MTX, plus lots of water, no caffeine (can’t have anyway due to heart problem), no folic acid on the day (only take one a week, the day after I take mtx) and activity. Interestingly, I chose to take my mtx on a Tuesday evening, thinking that if I’m not going to feel good, I’d rather feel bad at work than on the weekend! But maybe i should take it in the morning instead? I also don’t drink alcohol on my mtx day, but do on other days, always in moderation and normally only a couple a week.
I’ve had no side effects to date, but also no benefit yet. I’ve been on 15mg/week for 8 weeks, and now 20mg/week for a further 3 weeks. Plus 2g ssz/day. Any ideas what the magic dose is? My nurse plans to do increase to 25 if no benefit and then try Certolizumab pergol injections (don’t know another name for it) - any opinions?

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That’s good to know! Like a.laker28 said, WAY OVER MY HEAD–almost all of it!

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The important thing (IMO) is not the academics and whether or not it matters if you referring to the DNA that makes up the “protein” or just the prtein when referring to the immune response, We KNOW which Biologics are more likley to have antibodies developed afgainst them and we KNOW MTX slows that process down,

I have had a long relationship with MTX and learned how to get along with it. Yup it was strange that it went better switching to mornings and like a.laker28 settled in on Tues for injection day. My experience may or may not be helpful to others, but thought it was worth laying out there…

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Your experience certainly is worth laying out.

Mtx has an image problem. Partly that’s because of potential side effects, especially if taken orally. But I think there are other, less factual reasons for its bad rep. It is so often the first drug taken by people with inflammatory arthritis who may not have taken any ‘serious’ drugs before. In that situation it can get the blame for the various symptoms of the disease itself, as they gradually emerge. It is also less glamorous by far than the newer biologics.

Yet Mtx can be a very good drug indeed. If biologics were unavailable for some reason, I’d cling to Mtx all the more. Steroids helped me in the early days, but they’re not sustainable unless they absolutely have to be. Mtx does seem to be very sustainable for me and it helped considerably in terms of getting me out of my first long-lasting flare-up. And I’m pretty sure it continues to help alongside Humira.

Every now and then, the suspicion surrounding this long-used and very widely-used drug does get to me and I wonder whether it’ll just cause some massive problem out of the blue. Yet so far, so good - nearly 6 years on. I don’t have big bags under my eyes, or raised liver enzymes, or grey skin or any extra health issues or bad symptoms worthy of concern, I seem generally quite healthy.

And, in fact, I take Mtx pills at night and sometimes forget to drink enough water etc. etc. If it does cause side effects it is most definitely worth trying the injectable version and taking it at a different time and so on. But some of us just chuck it down our necks whenever and do just fine. It can indeed be that simple.


And even though I got the common side effects at the start, my body adjusted. So I’ve gone from from initially taking it on a Friday so i could be wiped out on Saturday, to necking it on a Monday night, and looking forward to a good nights sleep!


Yep…I grew immune to Humira after about a year but was not taking MTX. I have just now moved on to Remicade and it is the first thing that is working since Humira. Enbrel didn’t work at all.