This page shows what was measured, who it was measured in, and what that does not settle.
What Leflunomide does in the body
Active rheumatoid arthritis
DNA is built from two families of chemical letters, and an immune cell preparing to divide has to manufacture both. Leflunomide is inert until the body converts it into its working form, which then blocks the single enzyme that controls production of one of those families. Immune cells, which cannot get enough of these letters by recycling, stall. Most other cells can recycle enough to carry on. The working form is reabsorbed from the gut over and over instead of being excreted, so it stays in the body for months to years after the last tablet — which is why coming off it usually means taking a second drug to strip it out.
What happened in people
ACR20 response 52% on leflunomide against 26% on placebo and 46% on methotrexate in 482 patients over 52 weeks, P<0.001 against placebo
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
The limit that matters most
That leflunomide is an improvement on methotrexate — its own registration trial found the two statistically equivalent, with more liver-driven discontinuation
Where it acts
The mitochondrial inner membrane of activated lymphocytes, where dihydroorotate dehydrogenase sits and where the pyrimidine supply for a dividing immune cell is decided
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · G162GK9U4W · read 2026-08-29
Its recorded molecular formula is C12H9F3N2O2, weighing 270.2.
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 141 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Energy
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Energy
manifestations of systemic symptom fatigue
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
1 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
American College of Rheumatology success rate — completing 52 weeks of treatment and meeting ACR20 response criteria
Phase 3, randomised, double-blind, placebo- and active-controlled, 12 months
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
ACR20 response 52% leflunomide, 46% methotrexate, 26% placebo; success rate 41%, 35%, 19%; P<0.001 for both active arms against placebo, active arms statistically equivalent to each other
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Discontinuation for asymptomatic transaminase elevation was 7.1% on leflunomide against 3.3% on methotrexate and 1.7% on placebo. The trial was powered against placebo, not to distinguish the two active drugs, so "statistically equivalent" describes an absence of detected difference rather than a demonstrated equivalence.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, 10 mg and 20 mg
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
PubChem CID 3899 — leflunomide structure, formula and molecular weight (https://pubchem.ncbi.nlm.nih.gov/compound/3899) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 1 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.6 registered measures of this kind. No reviewed result.
■What a body can do day to dayEvidence recorded. Walking, dressing, breathing, recovering.1 registered measure of this kind.
■Measured performanceEvidence recorded. How much was lifted, how far was run, how fast.1 registered measure of this kind.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.3 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Mouse, Rat, Dog. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Leflunomide
What a person takes: Oral film-coated tablet, 10 mg and 20 mg.
The measurement behind this step
Rapidly and almost completely converted to teriflunomide, so leflunomide itself is not detectable in plasma at steady state. Teriflunomide is more than 99% protein bound with a very small volume of distribution and is cleared slowly through extensive enterohepatic recirculation, giving a half-life of roughly two weeks and measurable concentrations for up to two years after the last dose. Because of that, the label describes an accelerated drug elimination procedure using cholestyramine or activated charcoal, which reduces plasma concentrations substantially over about eleven days and is directed for pregnancy, suspected liver injury and certain treatment switches.
Getting in
Swallowed as a closed ring that opens in the body
The tablet contains an inert molecule. Almost as soon as it is absorbed, a chemical ring in it opens up, and the opened form is the drug.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Leflunomide is an isoxazole that undergoes ring opening to teriflunomide, a malononitrilamide, largely in the gut wall and liver and partly non-enzymatically. Conversion is essentially complete, and leflunomide itself is undetectable in plasma at steady state.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
Reaching the cell
The active form is recycled instead of excreted
Rather than being cleared, the working molecule is sent into the bile, reabsorbed from the gut, and sent round again. This is why it lasts for months.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Teriflunomide is over 99% protein bound with a very small volume of distribution and undergoes extensive enterohepatic recirculation, giving an elimination half-life of roughly two weeks and detectable plasma concentrations for up to two years. Cholestyramine or activated charcoal binds it in the gut, interrupts the loop and reduces concentrations over about eleven days.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
What it acts on
It blocks one enzyme on the mitochondrial membrane
Deep inside the cell, on the surface of the mitochondrion, sits the enzyme that controls production of one of the two families of DNA building blocks. The drug binds it and stops it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Teriflunomide binds dihydroorotate dehydrogenase, an inner mitochondrial membrane flavoenzyme coupled to the respiratory chain through ubiquinone, which catalyses the fourth and rate-limiting step of de novo pyrimidine synthesis — oxidation of dihydroorotate to orotate.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
The change it makes
Activated lymphocytes cannot expand their pyrimidine pool
Most cells in the body can recycle enough building blocks to get by. An immune cell that has just been activated needs roughly eight times more than usual and cannot recycle its way there, so it stalls.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Resting and most somatic cells meet their pyrimidine requirement through the salvage pathway; activated lymphocytes expand their pyrimidine pool approximately eightfold and depend on de novo synthesis. The dependence is demonstrable in vitro by uridine rescue. Teriflunomide additionally inhibits several tyrosine kinases at higher concentrations, with unquantified clinical contribution.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
What that does for a person
Symptoms improve and joint erosion slows
About half of patients met the standard response threshold at a year, against a quarter on placebo, and X-rays showed less new joint damage.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
ACR20 response 52% against 26% on placebo and 46% on methotrexate in 482 patients over 52 weeks, with mean time to initial response of 8.4 weeks. Radiographic progression was less than placebo at P=0.001, and physical function and quality of life improved at P<0.001.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
What that does for a person
The liver and a possible pregnancy are the two hard limits
The drug can injure the liver badly, and it must not reach a pregnancy. Both of those are made harder by the fact that stopping the tablets does not remove the drug for a very long time.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Boxed warnings for embryo-fetal toxicity and for severe liver injury including fatal liver failure. Discontinuation for asymptomatic transaminase elevation was 7.1% against 1.7% on placebo in the registration trial. Because teriflunomide persists for up to two years, both problems are managed with an accelerated elimination procedure rather than by discontinuation alone.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
manifestations of systemic symptom fever
manifestations of systemic symptom fatigue
quality of life sf 36 questionnaire
Measured
Things only a test, a scale or a device shows.
blood pressure
il 6 in plasma
Meaningful
Things that change how a life goes, not only a number.
remission according to das28 crp at week 16
remission according to das28 crp at week 52
remission according to das28 crp at week 104
remission rate
health assessment questionnaire disability index at week 12
relapse rate at 12 months
overall survival
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (28)
american college of rheumatology 20 responses
rate and extend of absorption
renal function
bioequivalence based on auc and cmax
acr20
treatment emergent adverse events
validated aid associated product technical failures
treatment emergent adverse events and serious adverse events
achieving good eular response at the end of 12 weeks
rheumatoid arthritis impact of disease total at week 24
maximum tolerated dose
clinical benefit rate
psoriatic arthritis disease activity
who are eligible consent and complete the 48 weeks study
manifestations of systemic symptoms chest congestion
emerging signs or symptoms of ischemia
signs or symptoms of ischemia
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. 18 to 19 days
Read from the label, which states: “Due to the very long half-life of teriflunomide (18 to 19 days), a loading dose of 100 mg for 3 days was used in clinical studies to facilitate the rapid attainment of steady-state teriflunomide concentrations.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with active rheumatoid arthritis, usually where methotrexate has failed or cannot be tolerated. It is also used off-label in psoriatic arthritis and, at times, in BK virus nephropathy after transplantation.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of leflunomide in pediatric patients have not been established.”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
On older people, the label states: “Of the total number of subjects in controlled clinical trials (Trials 1, 2, and 3) of leflunomide, 234 subjects were 65 years and over [see Clinical Studies (14)] .”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to leflunomide during pregnancy.”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
On people who are breastfeeding, the label states: “8.3 Females and Males of Reproductive Potential Leflunomide may cause fetal harm if administered during pregnancy [see Use in Specific Populations (8.1)] .”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
On people with reduced liver function, the label states: “Dedicated studies of the effect of hepatic impairment on leflunomide pharmacokinetics have not been conducted.”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
On people with reduced kidney function, the label states: “Dedicated studies of the effect of renal impairment on leflunomide pharmacokinetics have not been conducted.”
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
Where the result stopped carrying
Severe liver injury including fatal liver failure was reported after approval and is now the second half of a boxed warning
Transaminase elevations forced discontinuation in more than four times as many patients as placebo in the registration trial itself
The drug cannot be reliably withdrawn by stopping it: the active metabolite persists for up to two years and needs a chemical elimination procedure
It did not displace methotrexate as first-line conventional therapy, because it never showed a reason to
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral film-coated tablet, 10 mg and 20 mg
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S1, S3, S4, S6.
No source is stored against this line.
What is in the pack
Rapidly and almost completely converted to teriflunomide, so leflunomide itself is not detectable in plasma at steady state.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Teriflunomide is more than 99% protein bound with a very small volume of distribution and is cleared slowly through extensive enterohepatic recirculation, giving a half-life of roughly two weeks and measurable concentrations for up to two years after the last dose. Because of that, the label describes an accelerated drug elimination procedure using cholestyramine or activated charcoal, which reduces plasma concentrations substantially over about eleven days and is directed for pregnancy, suspected liver injury and certain treatment switches.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Two boxed warnings. Embryo-fetal toxicity: contraindicated in pregnancy, with teratogenicity and embryo-lethality in animals at exposures below the human level; pregnancy must be excluded before starting and effective contraception used during treatment and during the elimination procedure. Hepatotoxicity: severe liver injury including fatal liver failure has been reported; contraindicated in severe hepatic impairment; patients with pre-existing liver disease or baseline ALT above twice the upper limit of normal should not be treated; ALT monitored at least monthly for six months and then every six to eight weeks. Other labelled risks include serious infection including tuberculosis reactivation, interstitial lung disease, peripheral neuropathy, hypertension, severe cutaneous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, and blood dyscrasias.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
DailyMed: ARAVA (leflunomide) tablets, Sanofi-Aventis — boxed warnings for embryo-fetal toxicity and hepatotoxicity, and the accelerated drug elimination pro… · a recorded source, not a stored snapshot
Drugs@FDA: ARAVA (leflunomide), NDA 020905, Sanofi-Aventis — label and approval history (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=over… · a recorded source, not a stored snapshot
Reports sent to a regulator
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Leflunomide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 86720 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
rheumatoid arthritis — 14361 reaction mentions
drug intolerance — 10784 reaction mentions
pain — 9460 reaction mentions
arthralgia — 9066 reaction mentions
drug hypersensitivity — 8796 reaction mentions
joint swelling — 7797 reaction mentions
treatment failure — 7447 reaction mentions
rash — 7130 reaction mentions
alopecia — 5947 reaction mentions
condition aggravated — 5932 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral film-coated tablet, 10 mg and 20 mg
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Teriflunomide is more than 99% protein bound with a very small volume of distribution and is cleared slowly through extensive enterohepatic recirculation, giving a half-life of roughly two weeks and measurable concentrations for up to two years after the last dose. Because of that, the label describes an accelerated drug elimination procedure using cholestyramine or activated charcoal, which reduces plasma concentrations substantially over about eleven days and is directed for pregnancy, suspected liver injury and certain treatment switches.
No source is stored against this line.
What is recorded as being sold
49 products list this as an active ingredient in the United States drug directory. 49 of them contain it and nothing else.
FDA National Drug Code directory · 62332-061 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 62332-061 · read 2026-08-29
The regulator's established pharmacologic class for it is antirheumatic agent [epc].
FDA National Drug Code directory · 62332-061 · read 2026-08-29
25 published labels name it as an active ingredient. 25 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-29
Leflunomide is oral at 3 DOSAGE FORMS AND STRENGTHS Leflunomide tablets USP are available in two strengths: · Tablets: 10 mg, supplied as white to off white, circular, biconvex, film coated tablets debossed with ‘L115’ on one side and plain o…, recorded as fda label in effect 2024-08-20 in the United States.
US prescribing information · c288d1d3-3fbe-4c34-a28a-923d515809b3 · read 2026-08-30
Recorded price in US: 0.29167–0.32475 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 20 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Leflunomide studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That leflunomide is an improvement on methotrexate — its own registration trial found the two statistically equivalent, with more liver-driven discontinuation
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That lymphocyte selectivity through salvage-pathway dependence explains both the effect and the toxicity profile in humans; the demonstration is in cell culture
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That teriflunomide is a distinct therapeutic advance, when it is the active metabolite leflunomide already produces
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a smaller p-value against placebo for radiographic progression ranks leflunomide above methotrexate; that comparison was not made
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Leflunomide are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
US301: better than placebo, statistically equivalent to methotrexate
In plain words
The registration trial compared leflunomide against a dummy tablet and against methotrexate in 482 patients over a year. About half responded on leflunomide, about half on methotrexate, and about a quarter on placebo. The new drug beat placebo clearly, and did not beat the old drug.
What was measured
ACR20 response and success rate at 52 weeks, and radiographic progression, against placebo and against methotrexate
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A randomised, double-blind, placebo- and active-controlled 12-month study at 47 centres in the United States and Canada enrolled 482 patients with rheumatoid arthritis of at least six months’ duration and no previous methotrexate treatment, randomised to leflunomide 20 mg daily, placebo, or methotrexate 7.5 to 15 mg weekly. ACR20 response and success rates were 52% and 41% for leflunomide, 46% and 35% for methotrexate, and 26% and 19% for placebo (P<0.001 against placebo for both active arms), with the two active treatments described as statistically equivalent. Mean time to initial response was 8.4 weeks on leflunomide against 9.5 on methotrexate. Radiographic progression was less with leflunomide (P=0.001) and methotrexate (P=0.02) than placebo. Asymptomatic transaminase elevations caused discontinuation in 7.1% on leflunomide, 3.3% on methotrexate and 1.7% on placebo.
Written into the record, not signed off as a reviewed claim
Hepatotoxicity: transaminase discontinuations at four times the placebo rate, then a boxed warning
In plain words
Even in the registration trial, liver enzyme rises made people stop the drug four times as often as placebo. Severe liver injury including fatal liver failure was reported afterwards, and the label now carries a boxed warning and a monthly blood test schedule.
What was measured
Discontinuation for asymptomatic transaminase elevation, 7.1% against 1.7% on placebo, in the registration trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In the registration trial, asymptomatic transaminase elevations resulted in treatment discontinuation for 7.1% of leflunomide patients against 3.3% on methotrexate and 1.7% on placebo. The label now carries a boxed warning stating that severe liver injury, including fatal liver failure, has been reported in patients treated with the drug; that it is contraindicated in severe hepatic impairment; that concomitant use with other potentially hepatotoxic drugs may increase risk; and that patients with pre-existing acute or chronic liver disease or a baseline ALT above twice the upper limit of normal are at increased risk and should not be treated. It directs ALT monitoring at least monthly for six months after starting and every six to eight weeks thereafter, and, if drug-induced liver injury is suspected, stopping the drug, starting the accelerated elimination procedure and monitoring liver tests weekly.
Written into the record, not signed off as a reviewed claim
A drug you cannot simply stop taking
In plain words
The active form is reabsorbed from the gut over and over rather than being excreted, so it can still be detectable up to two years after the last tablet. Getting it out requires taking a second drug that interrupts the recycling, which brings the level down in about eleven days.
What was measured
Plasma teriflunomide concentration decline with and without an accelerated elimination procedure, as described on the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Teriflunomide is over 99% protein bound with a small volume of distribution and undergoes extensive enterohepatic recirculation, giving a half-life of roughly two weeks and plasma concentrations that may remain measurable for up to two years after discontinuation. The label describes an accelerated drug elimination procedure — cholestyramine or activated charcoal, which interrupt the recirculation — that reduces plasma concentrations substantially over about eleven days. The label directs that this procedure be used if pregnancy occurs, if serious liver injury is suspected, and before switching to certain other agents. This kinetic property, not potency, is what most distinguishes the drug clinically.
Source
ARAVA (leflunomide) tablets United States prescribing information, boxed warning, Warnings and Precautions and Clinical Pharmacology sections
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The embryo-fetal warning has to be read together with the half-life
In plain words
The drug is contraindicated in pregnancy, and animal studies showed harm at exposures below what a person receives. The difficulty is that stopping the tablets does not remove the drug for a very long time, so avoiding pregnancy has to be planned rather than reacted to.
What was measured
Teratogenicity and embryo-lethality in animals at exposures below the human clinical level, as stated on the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The boxed warning states that the drug is contraindicated for use in pregnant women because of the potential for fetal harm, that teratogenicity and embryo-lethality occurred in animals administered leflunomide at doses lower than the human exposure level, and that pregnancy must be excluded before starting treatment in females of reproductive potential. It directs effective contraception during treatment and during an accelerated drug elimination procedure after treatment, and directs stopping the drug and starting that procedure if a patient becomes pregnant. The clinical consequence of combining a contraindication in pregnancy with a metabolite detectable for up to two years is that discontinuation alone does not make the drug safe to conceive on, and the label handles this by making elimination an explicit procedure rather than a matter of waiting.
Source
ARAVA (leflunomide) tablets United States prescribing information, boxed warning "Embryo-Fetal Toxicity"
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Equivalence to methotrexate is not superiority, and the trial reported both drugs plainly
In plain words
Leflunomide arrived as the first new conventional drug for rheumatoid arthritis in years, and it was often described that way. What its own registration trial showed was that it performed about the same as the drug already in use, with more liver-enzyme problems.
What was measured
That leflunomide is an improvement on methotrexate — the registration trial found the two statistically equivalent on response, with more transaminase-driven discontinuation on leflunomide
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The registration trial reported ACR20 response of 52% for leflunomide and 46% for methotrexate and described them as statistically equivalent — a term that in this design means no significant difference was detected between the active arms, in a trial powered to distinguish each from placebo rather than from each other. A trial with 482 patients across three arms has limited power to detect a modest difference between two active drugs. What the trial does establish is that leflunomide is clearly better than nothing on both symptoms and radiographs. What it does not establish, and was not designed to, is a reason to prefer it over methotrexate in a patient who tolerates methotrexate — and the discontinuation figures for transaminase elevation, 7.1% against 3.3%, point the other way.
Written into the record, not signed off as a reviewed claim
The metabolite became a separate drug for a different disease
In plain words
Leflunomide is inert until the body turns it into teriflunomide. In 2012 teriflunomide itself was approved as a new medicine for multiple sclerosis, under its own patents, more than a decade after leflunomide had gone generic. The molecule doing the work was the same one all along.
What was measured
That teriflunomide represents a distinct therapeutic advance over leflunomide — it is the active metabolite leflunomide produces, developed for a different disease and priced accordingly
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Leflunomide is a prodrug that opens to teriflunomide, the malononitrilamide that inhibits dihydroorotate dehydrogenase. Teriflunomide was developed separately, tested in relapsing multiple sclerosis, and approved in 2012 with its own labelling, its own price and its own patent protection, while leflunomide had been generic in the United States since 2005. Both carry boxed warnings for hepatotoxicity and embryo-fetal toxicity, and both are subject to the same accelerated elimination procedure, because they are the same active species. Developing a known active metabolite for a new indication is a legitimate and reasonably common path, and the resulting situation — a generic drug and a branded drug that a patient’s liver cannot distinguish between — is worth stating plainly.
Source
ARAVA (leflunomide) United States prescribing information, Clinical Pharmacology (conversion to teriflunomide); Drugs@FDA record for ARAVA, NDA 020905
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
Radiographic progression slowed, which is the endpoint that matters most
In plain words
Beyond how people felt, the trial measured joint damage on X-ray after a year. Both leflunomide and methotrexate showed less progression than placebo, and leflunomide’s result was the stronger of the two by p-value.
What was measured
Radiographic disease progression at 12 months against placebo, in the intent-to-treat population
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
X-ray analyses in the registration trial demonstrated less disease progression with leflunomide (P=0.001) and with methotrexate (P=0.02) than with placebo. Both active treatments also improved physical function and health-related quality of life significantly more than placebo (P<0.001 and P<0.05 respectively). A structural endpoint is the strongest evidence available in rheumatoid arthritis short of long-term disability, because erosion is irreversible and symptom scores are not. The p-values should not be read as ranking the two active drugs against each other: each is a comparison against placebo, and a smaller p-value in one comparison does not establish superiority in a comparison that was not made.
Written into the record, not signed off as a reviewed claim
The selectivity argument depends on a salvage pathway the assays have to test for
In plain words
The reason this drug is supposed to hit immune cells and spare everything else is that most cells can recycle the building blocks it blocks, and activated immune cells cannot. That is well supported in cell culture and it is an inference about what happens in a person.
What was measured
That lymphocyte selectivity explains the clinical effect and the toxicity profile — the pathway dependence is established in cell culture, the human demonstration does not exist, and the drug has activities beyond DHODH
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Teriflunomide inhibits dihydroorotate dehydrogenase, the rate-limiting enzyme of de novo pyrimidine synthesis. Resting and most somatic cells meet their pyrimidine needs through the salvage pathway and are relatively unaffected; activated lymphocytes expand their pyrimidine pool roughly eightfold and depend on de novo synthesis to do so. This is demonstrable in vitro by the uridine rescue experiment, in which adding uridine to the medium restores proliferation. In humans the corresponding demonstration does not exist, and the drug additionally inhibits several tyrosine kinases at higher concentrations, an activity whose clinical contribution is unquantified. The observed toxicity profile — hepatic injury, diarrhoea, hypertension, peripheral neuropathy, interstitial lung disease — is not obviously confined to tissues lacking salvage capacity.
Source
ARAVA (leflunomide) United States prescribing information, Clinical Pharmacology, Mechanism of Action; Strand V et al., Arch Intern Med 1999;159:2542-2550
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
25 documents were read for this substance.
RNAWiki source record
25 of them state the same halfLife, and they agree.
RNAWiki source record
25 of them state the same proteinBinding, and they agree.
RNAWiki source record
25 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
G162GK9U4W
RxNorm concept
205284
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S1, S3, S4, S6.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
13 approved applications cover products containing this substance. The earliest was NDA020905, approved 19980910 to SANOFI AVENTIS US.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A prodrug whose active metabolite blocks the rate-limiting enzyme of pyrimidine synthesis and so starves dividing lymphocytes of the other half of the DNA alphabet — in its 482-patient registration trial it produced an ACR20 response in 52% against 26% on placebo and 46% on methotrexate, statistically superior to placebo and equivalent to methotrexate, and it carries boxed warnings for embryo-fetal toxicity and for severe liver injury including fatal liver failure.
Recorded evidence blocks (12)
Q2
What did Leflunomide's largest trial (2000 people) and its longest (32 years) measure?
2000 people in Leflunomide's largest registered study, 32 years in its longest registered window, measuring Mortality resulting from treatment, underlying disease, or unrelated causes. ClinicalTrials.gov · 2026-09-01
23 phase2, 18 phase1, 18 phase3, 16 phase4, 10 na, 3 na or unstated, 1 early phase1; NCT04725422; 2050-08; no ageing endpoint recorded. Last human test completed 2026, NCT06714461.
Interpretation These counts include studies where Leflunomide was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
23
phase1
18
phase3
18
phase4
16
na
10
na or unstated
3
2 more recorded rows
early phase1
1
Last recorded human testNCT06714461
2026-05-14
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Leflunomide shown lifespan?
Interpretation Mortality resulting from treatment, underlying disease, or unrelated causes — the recorded outcome words.
Show the evidence
mouse
lifespan
rat
mechanism-only
dog
lifespan
humanNCT00230035
lifespan; Mortality resulting from treatment, underlying disease, or unrelated causes; 82
recorded 2026-09-01 · last checked 2026-09-04
Q4
9 of Leflunomide's trials stopped: safety, accrual/recruitment, funding/business, other?
safety (3), accrual/recruitment (3), funding/business (1) and other (2): Leflunomide's stop wording, clustered. ClinicalTrials.gov · 2026-09-01
"Recommended by DSMB due to lack of accrual"; 9 of 82 registered studies
Show the evidence
Trial
NCT00230035
withdrawn; "Recommended by DSMB due to lack of accrual"
NCT00476996
terminated; "Recruitment was fully completed for this study; however, the study was terminated during conduct after the primary endpoint analysis was completed."
NCT01342016
terminated; "Due to safety concern of active control drug"
NCT01611675
terminated; "Adverse Events"
NCT02930343
terminated; "Due to time constraints, the study was halted prematurely"
NCT03952832
withdrawn; "Budget issues"
3 further recorded trials
NCT04361214
terminated; "Terminated by PI"
NCT04932564
terminated; "Issues with recruitment. Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care."
NCT05605587
terminated; "The study was prematurely terminated due to significant difficulties in recruiting participants, arising from the extremely rare nature of the targeted gene mutation."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Leflunomide used ARAVA® 20 mg tablets — over how long?
Leflunomide's half-life is 18 to 19 days — which schedules were studied?
18 to 19 days, the half-life Leflunomide's label states. openfda-label · fc044417-cd9a-42f6-8a3d-a14e7c2f81a2 · 2026-08-30
Show the evidence
half life
18 to 19 days; Due to the very long half-life of teriflunomide (18 to 19 days), a loading dose of 100 mg for 3 days was used in clinical studies to facilitate the rapid attainment of steady-state teriflunomide concentrations.
metabolism
12.3 Pharmacokinetics Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity.
recorded 2026-08-30 · last checked 2026-09-04
Q7
Which of achieving good eular response at the end of 12 weeks, acr20 and american college of rheumatology 20 responses did Leflunomide's trials measure?
achieving good eular response at the end of 12 weeks, acr20 and american college of rheumatology 20 responses lead 40 outcome terms across Leflunomide's trials. ClinicalTrials.gov · 2026-09-01
bioequivalence based on auc and cmax, remission according to das28 crp at week 16, remission according to das28 crp at week 52, remission according to das28 crp at week 104, remission rate and acr20 follow.
Show the evidence
american college of rheumatology 20 responses
1
rate and extend of absorption
1
renal function
1
bioequivalence based on auc and cmax
1
remission according to das28 crp at week 16
1
remission according to das28 crp at week 52
1
14 more recorded rows
remission according to das28 crp at week 104
1
remission rate
1
acr20
1
health assessment questionnaire disability index at week 12
1
treatment emergent adverse events
1
validated aid associated product technical failures
1
treatment emergent adverse events and serious adverse events
Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis; Dose limiting toxicity; latest 2050-08
Show the evidence
Trial
NCT03414502
"Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response"; n 400; "Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis"; 2029-03
NCT04212416
"Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease"; n 18; "Dose limiting toxicity"; 2027-06-17
NCT04370483
"Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma"; n 1; "Progressive disease"; 2026-11-10
NCT04508790
"Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma"; n 29; "Overall response"; 2027-02-14
NCT04725422
"CHronic Nonbacterial Osteomyelitis International Registry"; n 2000; "The change of CNO disease activity score"; 2050-08
NCT04997993
"Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer"; n 23; "Number of participants with Dose-limiting toxicities"; 2028-07
11 further recorded trials
NCT05014646
"Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients"; n 27; "Progression to multiple myeloma"; 2027-01-16
NCT05443425
"Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies"; n 18; "Incidence of adverse events"; 2027-01-05
NCT05626348
"The Clinical Efficacy of Immunomodulators in RA Patients"; n 400; "The percentage of patients who achieve clinical remission using European League Against Rheumatism (EULAR) response criteria DAS28."; 2026-12-31
NCT05937191
"Leflunomide for Idiopathic Pulmonary Hemosiderosis in Children"; n 34; "Times of pulmonary hemorrhage"; 2026-12-31
NCT05937880
"Leflunomide for Henoch-Schonlein Purpura"; n 36; "Rash frequency"; 2027-06-30
NCT06229340
"Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations"; n 20; "Objective response rate"; 2026-10-01
NCT06454383
"Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer"; n 19; "Dose limiting toxicities (DLTs)"; 2026-11-13
NCT06923488
"Leflunomide in Combination With Decitabine for Treatment of Relapsed or Refractory Myelodysplastic Syndromes"; n 26; "Percentage of incidences of regimen limiting toxicities (RLTs)"; 2028-10
NCT07138898
"Immunosuppressant Management in Rheumatology Patients Undergoing Elective Total Shoulder Arthroplasty"; n 80; "Incidence of wound complications"; 2028-01
NCT07709013
"Leflunomide to Prevent Cytomegalovirus Reactivation in Stem Cell Transplant Patients"; n 22; "Number of participants with clinically significant cytomegalovirus (CMV) infection"; 2029-04
NCT07730723
"The Effect of Nicorandil on Rheumatoid Arthritis Patients"; n 70; "Evaluation of treatment Efficacy"; 2027-07
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which 18 trials of Leflunomide posted no result?
Posted no result
18 of 18 completed trials
Registrations
NCT00001573, NCT00003293, NCT00946686, NCT00001863, NCT00652665 and NCT00653003, and 12 more
Completion dates
oldest 2000-05; newest 2022-11-22
Show the evidence
Trial
NCT00001573
2000-05
NCT00003293
2001-05
NCT00946686
2002-09
NCT00001863
2003-02
NCT00652665
2003-07
NCT00653003
2004-01
12 further recorded trials
NCT00637819
2004-07
NCT00563849
2004-08
NCT00003775
2006-05
NCT00004071
2007-09
NCT00101374
2008-05-21
NCT00596206
2009-10
NCT01774877
2014-08
NCT02644499
2017-09-15
NCT02703194
2019-01
NCT01727193
2021-11-18
NCT05007678
2022-07-01
NCT02981979
2022-11-22
Q10
At the median, Leflunomide's trials enrolled 65 people — anything larger?
Median enrolment
65
Largest enrolment
2000
Registered trials counted
80
Q11
What do 86720 spontaneous reports say about Leflunomide — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Leflunomide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 86720 reaction mentions were counted: rheumatoid arthritis 14361; drug intolerance 10784; pain 9460; arthralgia 9066. open-targets-adr · CHEMBL960 · 2026-06-24
Show the evidence
rheumatoid arthritis
14361
drug intolerance
10784
pain
9460
arthralgia
9066
drug hypersensitivity
8796
joint swelling
7797
4 more recorded rows
treatment failure
7447
rash
7130
alopecia
5947
condition aggravated
5932
recorded 2026-06-24 · last checked 2026-09-04
Q12
Leflunomide and CYP2C8: shared by which compounds?
CYP2C8 appear in Leflunomide's recorded interaction sentences, 1 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP2C8pharmacokinetics
The potential effect of Leflunomide on other drugs · CYP2C8 Substrates There was an increase in mean repaglinide C max and AUC (1.7 and 2.4-fold, respectively), following repeated doses of teriflunomide and a single dose of 0.25 mg repaglinide, suggesting that teriflunomide is an inhibitor of CYP2C8 in vivo .
recorded 2026-08-30 · last checked 2026-09-04
Q13
What is recorded about Leflunomide and autophagy?
"These findings identify mitochondrial dynamics as a therapeutic target in RA and suggest that leflunomide promotes apoptosis of RA-FLS by modulating the mitochondrial fission-autophagy axis." — where Leflunomide and autophagy appear together. Europe PMC · pathway abstract search · 2026-05-16
"These findings identify mitochondrial dynamics as a therapeutic target in RA and suggest that leflunomide promotes apoptosis of RA-FLS by modulating the mitochondrial fission-autophagy axis."
AMPK
PMID 37792678
"These observations collectively suggest that leflunomide controls obesity in part by activating AMPK and inducing lipophagy."
PMID 39113703
"Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway."
mTOR
PMID 41176424
"Steroid-sparing agents such as methotrexate, azathioprine, and leflunomide are widely used, while biologics, particularly anti-TNF agents, and emerging small-molecule inhibitors (e.g., JAK and mTOR inhibitors) offer additional options in refractory disease."
PMID 29540819
"Here we report that inhibition of S6K1 by A77 1726, the active metabolite of an anti-inflammatory drug leflunomide, induced mTOR feedback activation and ULK1<sup>S757</sup> phosphorylation in NSC34 cells, a hybrid mouse motoneuron cell line."
AMPKPMID 29540819
"Our study suggests that S6K1 inhibition induces autophagy through TAK1-mediated AMPK activation in NSC34 cells, and that blocking S6K1 activity by a small molecule inhibitor such as leflunomide may offer a new strategy for ALS treatment."
autophagy
PMID 29540819
"Our study suggests that S6K1 inhibition induces autophagy through TAK1-mediated AMPK activation in NSC34 cells, and that blocking S6K1 activity by a small molecule inhibitor such as leflunomide may offer a new strategy for ALS treatment."
PMID 33461007
"We recently reported that A77 1726, the active metabolite of the anti-inflammatory drug leflunomide, induces autophagy by activating AMP-activated protein kinase (AMPK) and Unc-51 like autophagy activating kinase 1 (ULK1)."
mTORPMID 28389629
"Here we report that feedback activation of mTOR in the PI-3 kinase pathway by two p70 S6 kinase (S6K1) inhibitors (PF-4708671 and A77 1726, the active metabolite of an immunosuppressive drug leflunomide) or by S6K1 knockdown did not suppress but rather induced autophagy."
recorded 2026-05-16 · last checked 2026-09-04
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