Methotrexate - a history lesson: This popped up in... - PMRGCAuk

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Methotrexate - a history lesson

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This popped up in my feed this morning to celebrate MTX's 75th birthday - I thought others might find it interesting.

medscape.com/viewarticle/98...

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75 Replies
katiemills profile image
katiemills

Thanks for posting this article . It was an interesting read !

123-go profile image
123-go

Fascinating! Thank you so much for sharing this.

Rachmaninov2 profile image
Rachmaninov2

It’s easy to understand how Dr. Farbers background inspired him to research which ultimately resulted in the development of Methotrexate. My personal celebration will be if and when Methotrexate enables me to live my life with less pain.

piglette profile image
piglette

Sidney Farber was an American pediatricpathologist. He is regarded as the father of modern chemotherapy for his work using folic acid antagonists to combat leukemia, which led to the development of other chemotherapeutic agents against other malignancies.

Farber speculated that because cancer cells divide rapidly, they need folate to support the rapid cell growth. He also thought that taking a drug that is a folate inhibitor, such as methotrexate, would slow the progress of cancer. In 1948 Sidney Farber reported the successful use of aminopterin, an anti-folate in the treatment of childhood leukemia.

Because of difficulty in manufacturing aminopterin, the compound was modified to offer easier synthesis; this modified compound was methotrexate. It was not until 1980 that additional beneficial effects of methotrexate in the treatment of patients with refractory RA appeared in the literature. In 1988 methotrexate won FDA approval for treating RA in the US. I was a trustee for Arthritis Care when it was announced for use in UK and I remember all the rheumatologists on the committee getting very exited and saying this drug would be revolutionary for rheumatoid arthritis.

PMRpro profile image
PMRproAmbassador in reply to piglette

That's basically what the article is about. I didn't know any of that aspect.

piglette profile image
piglette in reply to PMRpro

I do find the history of drugs quite fascinating. It also reminded me of the meeting when MTX was mentioned and the general excitement about it.

PMRpro profile image
PMRproAmbassador in reply to piglette

I find history of any sort exciting now. If only it had been different at school!

123-go profile image
123-go in reply to PMRpro

Kings and queens, dates, dates and dates 😩.

Rachmaninov2 profile image
Rachmaninov2 in reply to 123-go

I needed something to occupy my mind recently due to mobility problems so I made a list of all the British monarchs/rulers from Alfred the Great to Charles 111. I have to say there were some I hadn’t heard of. I wonder how the powers that be decide what we should be taught.

PMRpro profile image
PMRproAmbassador in reply to Rachmaninov2

I've never been THAT desperate!

Rachmaninov2 profile image
Rachmaninov2 in reply to PMRpro

Actually I found it very interesting, I can decide what I want to learn about unlike school.

PMRpro profile image
PMRproAmbassador in reply to Rachmaninov2

I love archaeology programmes!!

Rachmaninov2 profile image
Rachmaninov2 in reply to PMRpro

Yes, I used to enjoy the old Time Team programmes. I think for me a lot depends on the presenters. Did you see the programme where they discovered the tomb of Richard (11?/111?) ? I seem to remember that they found out that his scoliosis wasn’t as bad as was originally thought. I stand corrected if I’m wrong.

DorsetLady profile image
DorsetLadyPMRGCAuk volunteer in reply to Rachmaninov2

Richard 111 -Leicester car park ?

Rachmaninov2 profile image
Rachmaninov2 in reply to DorsetLady

That’s it! I like to find out about the person not just the dates.

DorsetLady profile image
DorsetLadyPMRGCAuk volunteer in reply to Rachmaninov2

Agree…

PMRpro profile image
PMRproAmbassador in reply to Rachmaninov2

The Alice Roberts series at present is great

Bcol profile image
Bcol in reply to PMRpro

Alice Roberts is excellent

PMRpro profile image
PMRproAmbassador in reply to Bcol

She is!

PRL1957 profile image
PRL1957 in reply to Rachmaninov2

I think the commonly held and often exaggerated image of Richard III's deformed body comes from some politically expedient propaganda by Shakespeare. Richard III was the last monarch from the House of York. Following his victory over the Yorkist army at Bosworth (near Leicester), Henry VII from the House of Tudor and decended from the House of Lancaster, became king. That effectively marked the end of the 'wars of the roses' between the houses of Lancaster and York - although there was one further battle (of Stoke). Shakespeare was writing when the Tudor/Lancastrian Elizabeth I ruled, so defaming or satirising Richard of York would play well to the monarchy.

Rachmaninov2 profile image
Rachmaninov2 in reply to PRL1957

Thank you for your response PRL1957, very interesting. I now have a greater understanding of the machinations of the time.

Blackcat1M profile image
Blackcat1M in reply to PMRpro

me too I drive my OH bonkers watching them

PMRpro profile image
PMRproAmbassador in reply to Blackcat1M

Hehe - mine's poison was old films and Midsommer Murders, ad nauseum. I couldn't bear them. Separate rooms, own TVs!

Blackcat1M profile image
Blackcat1M in reply to PMRpro

oh good idea hope you are feeling better x

123-go profile image
123-go in reply to Rachmaninov2

Whatever works for you, I say, but it didn’t work too well for a class of pubescent girls in the late 1950’s . Probably the ‘powers that were’ didn’t want us to get over-excited 😄.

Rachmaninov2 profile image
Rachmaninov2 in reply to 123-go

My school was for girls only, and looking back I remember the teachers as uninspiring.

123-go profile image
123-go in reply to Rachmaninov2

Mine too: me too.

AuthorJ profile image
AuthorJ in reply to Rachmaninov2

I recently finished Charles Spencer’s book The White Ship. It is an excellent history lesson of British royalty and very well written. In the time of William the conqueror

Rachmaninov2 profile image
Rachmaninov2 in reply to AuthorJ

Sounds interesting, thanks AuthorJ. I will check it out.

DorsetLady profile image
DorsetLadyPMRGCAuk volunteer in reply to PMRpro

We had a fantastic history teacher at senior school -made it so interesting and was also my form tutor for 4 out of the 5 years I was there.

Bcol profile image
Bcol in reply to DorsetLady

Sadly, if the lessons of history had been/were taken on board then an awful amount of today's problems wouldn't have happened/taken place. I love history, but my biggest problems is that those in power, wherever they are across the world, refuse to learn from it.

PMRpro profile image
PMRproAmbassador in reply to Bcol

Just reading Berlin - the Russian advance against the Germans. The machinations of Stalin - and they think they can trust Putin ...

Bcol profile image
Bcol in reply to PMRpro

I am unable to comment on that on this forum and hope to remain a member.

piglette profile image
piglette in reply to PMRpro

I agree. I did not even do history O level.

PMRpro profile image
PMRproAmbassador in reply to piglette

Me neither - you had to choose at third year whether you were a scientist or not. I was one of a few girls doing chemistry, even fewer doing physics.

piglette profile image
piglette in reply to PMRpro

I did physics with chemistry for O level a double whammy in one. I assume easier than doing them separately for us thickos!!

PMRpro profile image
PMRproAmbassador in reply to piglette

The only science the "thickos" did was compulsory biology!

piglette profile image
piglette in reply to PMRpro

Ah I didn’t do that, so perhaps I am not a thicko!

PMRpro profile image
PMRproAmbassador in reply to piglette

Anything with physics in is hard ...

piglette profile image
piglette in reply to PMRpro

Ah, I did Physics A level!!

PMRpro profile image
PMRproAmbassador in reply to piglette

Show off!!!!

piglette profile image
piglette in reply to PMRpro

and Pure Maths and Applied Maths and Further Maths and Additional Maths!!!

PMRpro profile image
PMRproAmbassador in reply to piglette

Major show-off! OH did double difficult sums for A levels together with physics. There was something else but I can't remember what - could have been additional maths. Then he did physics at uni. Strange person ...

piglette profile image
piglette in reply to PMRpro

I gave up after A level. I just loved maths and you did not need to revise for it. A major plus for lazy teenagers.

PMRpro profile image
PMRproAmbassador in reply to piglette

My class had the same useless female teacher for 3 consecutive years, the parallel class had the brilliant guy. She eventually went off with a mental breakdown and he had the job of catching up 2 years of missed stuff for O-level. He did a sterling job but it was still a lack of basic knowledge that made my attempt at A-level a big struggle so I gave up.

piglette profile image
piglette in reply to PMRpro

I had good ones and bad ones and nutty one!!

Balletomane profile image
Balletomane in reply to PMRpro

Oh dear, I'm going to add to that. Besides the Physics A level and all the maths, I did Physics S level, plus went to the Chemistry A level lessons without doing any exams, which made it even more fun. (The Head said I was doing enough exams, but let me continue chemistry as the time table allowed it. Wish all learning was like that.) And went on to a Physics degree. And, oh yes, my mother was the Physics teacher. She was hoping, as I also loved them, that I'd do Languages and Literature A levels, or so she said, with a smile.

PMRpro profile image
PMRproAmbassador in reply to Balletomane

I hated languages other than English then - love them now and have combined science and language for most of my working life. But maths and physics? No, left them to OH!

PMRCanada profile image
PMRCanada

Thanks for posting this. Very interesting.

Grammy80 profile image
Grammy80

A little added history....

The Dana-Farber Cancer Center in Boston, Massachusetts is renowned. It is a mecca for people around the world seeking cancer treatment.

In 1947 Dr. Farber founded the Children's Cancer Research Foundation and in 1969 the Foundation expanded to include patients of all ages. In 1974 it became the Sidney Farber Cancer Institute, to honor its founder. The change to its present name was in 1983 to recognize the long term support of Charles A. Dana Foundation who had long financed the Institute and its research.

Having lived on the East Coast of the states I know many people who were given added life and quality of life because of treatment there. Just recently a 34 year old son-in-law of a friend who had stage 4 melanoma and underwent intense treatment and is now in year two cancer free. Another friend whose husband was diagnosed with lymphoma at age 23 was treated there until his passing at age 89 last year; he was a working Maine woods lumberman and arborist all of those years!

(I hope I'm not out of line or off-piste, as you say, in writing this)💞

123-go profile image
123-go in reply to Grammy80

Remarkable and uplifting! The question I’d like to ask right now wouldn’t be appropriate in this forum but thank you!

Grammy80 profile image
Grammy80 in reply to 123-go

Send me a message.....😉

123-go profile image
123-go in reply to Grammy80

👍

HeronNS profile image
HeronNS

Interesting, although the first thing that really caught my interest was the incorrect claim that thalidomide was originally intended to relieve nausea in pregnant women. I distinctly remember my father, a GP at that time, saying that thalidomide had not been approved for that use. He was pretty disgusted by what had been happening and it appears, thankfully, that he'd had no part in it. Thalidomide was supposed to be a sedative but was found through use to alleviate nausea.

Merryfield profile image
Merryfield

Very interesting how the same drug can have diverse uses. I take gabapentin for back pain at night but it is also prescribed for anxiety.

PMRpro profile image
PMRproAmbassador in reply to Merryfield

Basically - all drugs have "side" effects. If there is a side effect that fits a need - it is used for that. These days they call it "repurposing".

Merryfield profile image
Merryfield in reply to PMRpro

That is an interesting way of looking at it. Never thought of serendipitous repurposing as side effects🌝

Grammy80 profile image
Grammy80 in reply to Merryfield

Having lost sight in my left eye from undiagnosed GCA, my opthalmologist kept a close watch on my right eye. When my visual field worsened, I was referred to a neuro-opthalmologist who diagnosed me with occipital neuralgia, right optic nerve. He prescribed Gabapentin, 100mg x three; after a year, I have a small blind spot in that eye. Woohoo! Previously, over 40% of it was dark when tested monthly. I'm thankful for repurposing!!💞

Merryfield profile image
Merryfield in reply to Grammy80

So glad gaba has such an important use for your sight!!

Grammy80 profile image
Grammy80 in reply to Merryfield

AMEN....my GP said it made no sense....and didn't understand or like it....but I guess that is why one fellow is a specialist and the other not!💞 They are all important....but let's have a bit of respect.

PMRpro profile image
PMRproAmbassador in reply to Grammy80

Doesn't have to make sense - has to work ...

Grammy80 profile image
Grammy80 in reply to PMRpro

D____ straight!!💞

Bcol profile image
Bcol

Fascinating read, thank you.

redruth123 profile image
redruth123

Fascinating insight into the use and re-purposing of drugs. Thanks for posting.

LemonZest11 profile image
LemonZest11

Fascinating, thanks.

AutoAnnie profile image
AutoAnnie

fascinating!

Thanks for that - a really interesting read.

Katietee profile image
Katietee

Very interesting - thank you!

Arniestal profile image
Arniestal

My partner was on methotrexate for rheumatism. He now has scarred lungs and has been told he has approx 3 years! Is this right when the scarring is caused by drugs or is it for when caused by copd etc

PMRpro profile image
PMRproAmbassador in reply to Arniestal

MTX can cause pulmonary fibrosis as an adverse effect and it is very important that any lung problems are reported for screening. It is the drug that causes it but ironically, MTX is associated with reduced rates of exacerbations of COPD in patients who take it.

Rugger profile image
Rugger

Very interesting. When I commented to my Rheumatologist on the vast number of potential side-effects of MTX, she said it had been around a long time and, of course, everything has to be reported. I didn't know that it was as old as I am.....! 🤣

PMRpro profile image
PMRproAmbassador in reply to Rugger

Like pred - not a lot to be found out about either! Similar ages too.

jarn profile image
jarn

Interesting read and for me, particularly, the use of MTX for psoriasis in early times. Whereas the ust of Toscilizimab (TCZ) irritated my psoriasis! Nice to see that these drugs can be put to good use. Thank you, PMRpro

Poshcards profile image
Poshcards

Thanks, an interesting read xx

Gurt profile image
Gurt

My husband, after 10 year on prednisolone will be moved to this drug. The details will be shared with him after extensive testing; he will be given the injection. Seems its much less invasive? Many possible side effects, but seems he will not have to use it forever for his PMR.

PMRpro profile image
PMRproAmbassador in reply to Gurt

By definition, injections are more invasive than pills but that aside - has he been led to believe that MTX will get him off pred altogether? If so, that is stretching reality considerably! For a small group of patients, it will work very well but not necessarily get them off pred altogether though some do. For others it may get them to a slightly lower dose of pred but no more. And it does have considerable potential for adverse effects - I lasted a month before I stopped and never went back on it, The fatigue was overwhelming and I had so-called pred effects I had never suffered in years on prednisolone and prednisone. There are no good large-scale studies showing it reduces the pred dose - and one of the small ones used to justify its use did a follow-up after 5 years which found that even though it did reduce the MTX dose, it didn't reduce any of the pred-related adverse effects. Which begs the question - why bother to add another layer of quite unpleasant side effects? Rheumatologists claim that in RA (where it does work) it is well tolerated and effective. In fact, it works well and has no intolerable side effects for a third of patients, for a third they can't cope with it and for a third it simply doesn't show any effect after 6-12 months.

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