Thread by @RheumTweeter

#Methotrexate is the nr1⃣drug of choice for Rheumatoid #Arthritis.

MTX's history is eventful, and deserves a 🧵

🔹It started with childhood leukeamia
🔹Sleeping Beauty in the 1960-70's
🔹Awakened by Hoffmeister
🔹FDA👍1988 and 🔝 in the 1990's

1/🧵 #RheumTwitter #MedTwitter

The start:
🔹1948, Dr Farber treated 5 children with #leukemia with Aminopterin, an anti-folate & precursor of #MTX, with outstanding results

🔹1951, first positive results of Aminopterin in #RA & #Psoriasis pts

Despite this, Aminopterin was aborted in RA

2/🧵 #RheumTwitter

MTX enters:
Due to difficulties in manufacturing, Aminopterin was modified and MTX was created.

🔹1962, positive results with MTX in both RA and #PSA

🔹Next 10 years: MTX was extensively studied in #psoriasis but halted in #RA

🔹In RA, MTX becomes the Sleeping Beauty👸💤

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MTX 💤:
In 1950, Dr P. Hench received the Noble Prize for the study of corticosteroids in RA.

⏬

🔹Rheumatologists were impassive in using MTX in RA due to
1⃣♥️Love for corticosteroids
2⃣Concerns for use of anti-cancer drug for a “benign disease” such as RA⁉️

4/🧵 #MedTwitter

MTX awakens:
🔹1972, Dr Hoffmeister, a practicing rheumatologist reported 🔝effects with MTX (10-15 mg/week) in 29 pts with RA

🔹11 had “major” improvements
🔹14 had “moderate” improvements
🔹treated for up to 25 months.
🔹80% flared when MTX<10mg/week

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Resistance:
🔹The outstanding results, by Dr Hoffmeister were only published as an abstract due to:

"the response to my abstract at the meeting was so negative that I did not want to spend the time submitting a manuscript only to have it rejected."

6/🧵 #RheumTwitter #RheumEdu

MTX gains traction:

🔹Several practising rheumatologists reported positive results during the next 5 years 🎉

🔹Despite this, placebo-controlled studies with #methotrexate in #rheumatoid #arthrits where not performed until the mid-1980s ❗️

7/🧵 #RheumTwitter #MedTwitter

2 pivotal RCT studies lead to MTXs FDA approval in 1988
🔹Weinblatt: 24-week with 35 pts bit.ly/3ulhwU3
🔹Williams: 18-week with 189 pts bit.ly/3iAyzPv

2 smaller studies with positive results
🔹 bit.ly/3ulM7B2 & bit.ly/3B509KQ

8/🧵 #RheumEdu

MTX investigations moved along two parallel lines:
🔹long-term, open studies
🔹active comparator trials

Results:
🔹Sustained response
🔹⬆️Function + ⬇️ESR
🔹⛰️Highest retention rates
🔹MTX superior to all other DMARDs

⏩Early 1990s, MTX was🥇RA therapy

9/🧵 #RheumTwitter

This thread is a condensation of the great article by Dr Michael E. Weinblatt, who played a pivotal role in the implementation of #MTX

It'a a great read, and I can highly recommend it! bit.ly/3F1gsJZ

10/🧵 #RheumEdu #RheumTwitter #MedTwitter