METHOTREXATE
Considered a cornerstone of Rheumatoid Arthritis treatment among other autoimmune conditions
FDA approved in 1988 for the treatment of #rheumatoidarthritis but DISCOVERED in the 1940s
⁉️ why the delay ⁉️
here is the (short)story 🧵
#meded #rheumtwitter
Considered a cornerstone of Rheumatoid Arthritis treatment among other autoimmune conditions
FDA approved in 1988 for the treatment of #rheumatoidarthritis but DISCOVERED in the 1940s
⁉️ why the delay ⁉️
here is the (short)story 🧵
#meded #rheumtwitter
Dr Sidney Farber, pediatric pathologist, considered a founder of chemotherapy
recognized folic acid is important for DNA synthesis
🌟cancer needs more DNA synthesis
🌟Aminopterin developed to BLOCK folic acid and decrease cancer cell growth
🌟Used to treat childhood Leukemia
recognized folic acid is important for DNA synthesis
🌟cancer needs more DNA synthesis
🌟Aminopterin developed to BLOCK folic acid and decrease cancer cell growth
🌟Used to treat childhood Leukemia
Methotrexate, a similar molecule was found to be better tolerated and easier to administer 
Recognized early a side effect of Folic Acid antagonism is immune suppression
⁉️ A ha! why not use lower doses to treat autoimmune disease ⁉️
1951 a trial of Aminopterin in Rheumatoid Arthritis AND Psoriasis
with ➕ results!
⁉️ A ha! why not use lower doses to treat autoimmune disease ⁉️
1951 a trial of Aminopterin in Rheumatoid Arthritis AND Psoriasis
with ➕ results!
Dermatology went on to use folic acid antagonism for psoriasis
🌟 Rheumatologists hesitant to use a chemotherapy on a "benign" disease
➕ steroids discovered
➕we had 🪙 GOLD to inject and that kind of worked!
So, Methotrexate languished for RA until...
🌟 Rheumatologists hesitant to use a chemotherapy on a "benign" disease
➕ steroids discovered
➕we had 🪙 GOLD to inject and that kind of worked!
So, Methotrexate languished for RA until...
1971-Rex Hoffmeister
29 cases of RA treated with MTX
11 patients had "Major clinical improvement"
only published in abstract
🌟got pushback, many saying dangerous to use drug
🌟1983 showed data treating patients for 15 YEARS! with good results + safety
29 cases of RA treated with MTX
11 patients had "Major clinical improvement"
only published in abstract
🌟got pushback, many saying dangerous to use drug
🌟1983 showed data treating patients for 15 YEARS! with good results + safety
Then a flourish of trials demonstrating efficacy and safety in 80s, 90s
even demonstrating slowing progression of radiographic damage
it took 40 years since drug discovery, but Rheumatoid Arthritis finally got a drug that is both safe and efficacious!
even demonstrating slowing progression of radiographic damage
it took 40 years since drug discovery, but Rheumatoid Arthritis finally got a drug that is both safe and efficacious!
References:
Weinblatt ME. Methotrexate: who would have predicted its importance in rheumatoid arthritis? Arthritis Res Ther. 2018
Weinblatt ME. Methotrexate: who would have predicted its importance in rheumatoid arthritis? Arthritis Res Ther. 2018
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