This page shows what was measured, who it was measured in, and what that does not settle.
What Azathioprine does in the body
Starving that supply stops the immune response before it can be mounted.
Azathioprine is swallowed as an inert molecule and broken apart in the body into 6-mercaptopurine, which cells then convert into counterfeit versions of the building blocks used to make DNA. Immune cells are hit hardest because when they are activated they must divide fast, and unlike most cells in the body they cannot recycle old building blocks — they have to make new ones. Two enzymes decide how much of the counterfeit accumulates in any given person, and the genes for them vary enough that some people accumulate a dangerous amount at an ordinary dose.
Why people take it. Stopping the immune system rejecting a transplanted kidney, and severe rheumatoid arthritis that has not responded to other treatment
What happened in people
Loss-of-function TPMT alleles in about 0.3% of people of European or African ancestry, and loss-of-function NUDT15 in 2% of people of East Asian ancestry, both stated on the label
✎ 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.
That starting the drug early in Crohn’s disease changes the course of the disease — the trial designed to show it did not
Where it acts
Dividing lymphocytes. The drug works because T and B cells depend almost entirely on de novo purine synthesis, while most other tissues can use the salvage pathway instead.
Kind of result
What a body can do day to day
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 · MRK240IY2L · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 155 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
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.
Corticosteroid-free clinical remission at week 26 in Crohn’s disease
✗ The study did not show it
Who was studied
SONIC (NCT00094458)
How many people
508
Study design
Phase 3, randomised, double-blind, three-arm
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Azathioprine alone 30.0% against infliximab alone 44.4% and combination 56.8%; P<0.001 for combination against azathioprine
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Azathioprine monotherapy was the comparator arm and lost on both remission and mucosal healing (16.5% against 43.9%). Serious infections were similar across arms at 3.9% to 5.6%, which undercuts the usual assumption that combining immunosuppressants necessarily multiplies infection risk.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
44.1% against 36.5%; difference 7.6% (95% CI -9.2 to 24.4), P=0.48
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Discontinuation for adverse events was 20.6% against 6.35% (P=0.02). A post hoc analysis using a higher activity threshold did favour azathioprine (11.8% against 30.2%, P=0.01) and is frequently cited as though it were the trial result.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
Interval reported. 95% CI -9
Written into the record, not signed off as a reviewed claim.
Terminated at interim analysis: 8 deaths against 1 (P=0.01) and 23 hospitalisations against 7 (P<0.001) with no physiological or clinical benefit
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The combination — prednisone, azathioprine and N-acetylcysteine — had been standard practice for idiopathic pulmonary fibrosis for years without a placebo-controlled trial. The arm was stopped at a mean follow-up of 32 weeks with roughly half the planned data.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Incidence of lymphoproliferative disorder by thiopurine exposure status
✓ The study showed what it set out to show
Who was studied
CESAME prospective cohort (Beaugerie 2009)
How many people
19486
Study design
Prospective nationwide observational cohort, not randomised
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Multivariate-adjusted hazard ratio 5.28 (95% CI 2.01 to 13.9), P=0.0007, current users against never-users; incidence 0.90 against 0.26 per 1,000 patient-years
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. Observational and therefore open to confounding by indication. Only 23 events occurred in total, which is why the confidence interval spans a sevenfold range. Median follow-up was 35 months, short for a cancer endpoint.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 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 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.
Where a source records it acting
Immune and lymphatic system: Immunosuppressive: delayed hypersensitivity and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses, and lymph node hyperplasia was inhibited in an animal arthritis model
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
Kidneys: Used for inhibition of renal homograft rejection; the label records that the mechanism for this action is somewhat obscure, and that the drug suppresses hypersensitivities of the cell-mediated type
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
Start
Azathioprine
What a person takes: Oral tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt.
The measurement behind this step
Roughly 88% of an oral dose is absorbed. The molecule is a prodrug twice over: azathioprine releases 6-mercaptopurine, which must then be converted to thioguanine nucleotides inside cells before anything happens. The clinical effect takes weeks to months to appear because it depends on turnover of the existing lymphocyte population, which is why it is never used to treat an acute flare on its own.
Getting in
Swallowed with a chemical wrapper that survives the stomach
Azathioprine is a delivery device for a second molecule. On its own it does nothing; it exists so that 6-mercaptopurine can survive being swallowed and reach the bloodstream.
╌╌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
A nitroimidazolyl thioether of 6-mercaptopurine, designed by Elion and Hitchings specifically to slow the release of 6-MP and reduce its first-pass loss. Cleavage is largely non-enzymatic, by glutathione and other cellular thiols attacking the activated nitroimidazole ring.
Inside cells, the body’s own antioxidant molecules break the link and release the working drug. This happens throughout the body, not in one organ.
╌╌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
Glutathione-mediated nucleophilic attack releases 6-mercaptopurine and 1-methyl-4-nitro-5-thioimidazole. Roughly 88% of an oral dose is absorbed; the released 6-MP then enters a branching metabolic network with three competing fates.
Three enzymes compete for it, and two of them are gatekeepers
The released drug can be turned into the active form, methylated into an inactive form, or oxidised into waste. How much ends up active depends on two enzymes whose genes vary between people.
╌╌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
Hypoxanthine-guanine phosphoribosyltransferase begins the activation route to 6-thioguanine nucleotides. Thiopurine S-methyltransferase diverts 6-MP to inactive 6-methylmercaptopurine, and xanthine oxidase oxidises it to 6-thiouric acid. NUDT15 additionally dephosphorylates active thioguanine triphosphates back to inactive monophosphates. TPMT and NUDT15 loss-of-function variants shift the balance towards accumulation, and xanthine oxidase inhibition by allopurinol does the same.
Counterfeit nucleotides go into DNA and block new purine synthesis
The active form is incorporated into the cell’s DNA in place of a real building block, and it also shuts down the factory that makes those building blocks from scratch.
╌╌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
6-thioguanine nucleotides are incorporated into DNA and RNA, and the intermediate 6-thioinosine monophosphate inhibits the first committed step of de novo purine synthesis, amidophosphoribosyltransferase. A separate and probably important mechanism is 6-thio-GTP binding to Rac1 in T cells, blocking the co-stimulatory signal and inducing apoptosis — the effect that best explains the drug’s selectivity for activated T cells.
Activated lymphocytes cannot divide, so the immune attack does not happen
Immune cells must multiply rapidly to mount a response. Most other cells in the body can recycle old building blocks; lymphocytes largely cannot, which is why they are hit hardest.
╌╌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
Lymphocytes depend disproportionately on de novo purine synthesis rather than the hypoxanthine salvage pathway, which is the basis of the therapeutic window for this whole antimetabolite class. The clinical effect takes weeks to months to develop because it depends on turnover of the existing lymphocyte pool, not on immediate inhibition.
Bone marrow and long-term cancer risk come from the same mechanism
The bone marrow is also full of rapidly dividing cells, so it is affected too. And a mechanism that damages DNA and suppresses immune surveillance over years carries a measured cancer risk.
──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
Myelosuppression is dose-limiting and is severe in TPMT- or NUDT15-deficient patients. Thioguanine incorporated into DNA sensitises skin to ultraviolet A, and prolonged suppression of Epstein-Barr-specific T-cell surveillance underlies the lymphoproliferative signal — an adjusted hazard ratio of 5.28 in current users against never-users in 19,486 followed patients, returning towards baseline after discontinuation.
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 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.
Kidney transplant recipients, people with rheumatoid arthritis unresponsive to other treatment, and — off the licensed indication but at very large scale — people with inflammatory bowel disease, autoimmune hepatitis, myasthenia gravis, vasculitis and lupus.
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: “Safety and efficacy of azathioprine in pediatric patients have not been established.”
US prescribing information · 2f994aed-f8e7-4967-a167-b22b783b4192 · read 2026-08-30
On people who are pregnant, the label states: “Teratogenic Effects: Pregnancy Category D: See WARNINGS section.”
US prescribing information · 2f994aed-f8e7-4967-a167-b22b783b4192 · read 2026-08-30
On people who are breastfeeding, the label states: “The use of azathioprine in nursing mothers is not recommended.”
US prescribing information · 2f994aed-f8e7-4967-a167-b22b783b4192 · read 2026-08-30
Where the result stopped carrying
AZTEC found no significant benefit over placebo at 76 weeks in newly diagnosed Crohn’s disease, with three times the discontinuation rate for adverse events
SONIC placed azathioprine monotherapy last of three arms on both remission and mucosal healing
PANTHER-IPF was stopped early because the combination containing azathioprine increased death and hospitalisation in pulmonary fibrosis
Mycophenolate displaced it as the standard transplant antimetabolite in the 1990s on the strength of head-to-head rejection data
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 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 (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
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
Given by a clinician
❝ 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 tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
✎ 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
Roughly 88% of an oral dose is absorbed. The molecule is a prodrug twice over: azathioprine releases 6-mercaptopurine, which must then be converted to thioguanine nucleotides inside cells before anything happens.
✎ 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: The clinical effect takes weeks to months to appear because it depends on turnover of the existing lymphocyte population, which is why it is never used to treat an acute flare on its own.
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.
The recorded stepping schedule
What follows is the schedule printed on the label, recorded as it is written there. It is a record of what was done, not a recommendation.
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
Initial dose (rheumatoid arthritis): Approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice-daily schedule
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
Beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals (rheumatoid arthritis): Dose increments of 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day — Recorded as applying where there are no serious toxicities and the initial response is unsatisfactory
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
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
Boxed warning for malignancy: chronic immunosuppression with a purine antimetabolite increases the risk of malignancy in humans, with post-transplant lymphoma and hepatosplenic T-cell lymphoma specifically named. Dose-limiting myelosuppression, severe and potentially fatal in patients deficient in TPMT or NUDT15, whose testing the label addresses. Serious and fatal interaction with xanthine oxidase inhibitors, allopurinol and febuxostat. Increased susceptibility to infection, hepatotoxicity, pancreatitis, a hypersensitivity syndrome with fever and rash that can mimic sepsis, and photosensitivity with an associated non-melanoma skin cancer risk.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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 tablet (50 mg, and 75 mg and 100 mg as Azasan) and intravenous sodium salt
✎ 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
The molecule is a prodrug twice over: azathioprine releases 6-mercaptopurine, which must then be converted to thioguanine nucleotides inside cells before anything happens.
✎ 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 which forms are sold. The rest of the recorded wording: The clinical effect takes weeks to months to appear because it depends on turnover of the existing lymphocyte population, which is why it is never used to treat an acute flare on its own.
No source is stored against this line.
What is recorded as being sold
45 products list this as an active ingredient in the United States drug directory. 45 of them contain it and nothing else.
FDA National Drug Code directory · 72789-129 · read 2026-08-29
They are sold as injection, powder, lyophilized, for solution, powder and tablet, taken intravenous and oral.
FDA National Drug Code directory · 72789-129 · read 2026-08-29
The regulator's established pharmacologic class for it is nucleic acid synthesis inhibitors [moa], nucleosides [cs] and purine antimetabolite [epc].
FDA National Drug Code directory · 72789-129 · read 2026-08-29
21 published labels name it as an active ingredient. 21 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 2f994aed-f8e7-4967-a167-b22b783b4192 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 2f994aed-f8e7-4967-a167-b22b783b4192 · read 2026-08-29
Azathioprine is tablets at 50 mg (as supplied by this distributor), recorded as prescription product; fda label in effect 2025-05-19 in the United States.
US prescribing information · 040d010a-b1b2-4db7-905d-8aa7f1bab0cd · read 2026-08-28
Recorded price in US: 0.12486–7.64868 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 13 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 Azathioprine 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 starting the drug early in Crohn’s disease changes the course of the disease — the trial designed to show it did not
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 the measured lymphoma excess is entirely attributable to the drug rather than partly to the disease it treats
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 an unlicensed use with long-standing practice behind it has evidence behind it; the label covers two indications and the drug is used for a dozen
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 the drug remains a first-line choice on efficacy, when all three head-to-head comparisons on this page place it behind the alternative
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 Azathioprine 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.
AZTEC: early azathioprine did not beat placebo in newly diagnosed Crohn’s disease
In plain words
The reasoning was that starting an immunosuppressant early, before damage accumulates, would change the course of Crohn’s disease. A blinded trial gave azathioprine or placebo to adults diagnosed within the previous eight weeks. After a year and a half, the two groups were not meaningfully different, and more people stopped the drug because of side effects.
What was measured
Sustained corticosteroid-free remission at 76 weeks, against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
AZTEC randomised 131 adults diagnosed with Crohn’s disease within the previous 8 weeks at 31 Spanish hospitals to azathioprine 2.5 mg/kg/day (n=68) or placebo (n=63), with corticosteroids permitted but no other concomitant medication. After 76 weeks, sustained corticosteroid-free remission was achieved by 30 (44.1%) against 23 (36.5%), a difference of 7.6% (95% CI -9.2 to 24.4, P=0.48). Relapse rates using a Crohn’s Disease Activity Index threshold of 175 and corticosteroid requirements were similar. A post hoc analysis using a threshold of 220 did favour azathioprine (11.8% against 30.2%, P=0.01). Serious adverse events occurred in 20.6% against 11.1% (P=0.16), and discontinuation for adverse events in 20.6% against 6.35% (P=0.02).
Written into the record, not signed off as a reviewed claim
SONIC: azathioprine alone was the weakest of the three arms
In plain words
Five hundred and eight people with moderate to severe Crohn’s disease who had never had either drug were randomly given azathioprine, infliximab, or both. Three in ten were in remission off steroids at six months on azathioprine, four and a half in ten on infliximab, and nearly six in ten on the combination.
What was measured
Corticosteroid-free clinical remission and mucosal healing at week 26, three-arm randomised comparison
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SONIC randomised 508 immunosuppressive-naive and biologic-naive adults with moderate-to-severe Crohn’s disease. Corticosteroid-free clinical remission at week 26 was 51 of 170 (30.0%) on azathioprine 2.5 mg/kg/day alone, 75 of 169 (44.4%) on infliximab alone, and 96 of 169 (56.8%) on the combination — P<0.001 for combination against azathioprine and P=0.006 for infliximab against combination. Mucosal healing at week 26 was 18 of 109 (16.5%), 28 of 93 (30.1%) and 47 of 107 (43.9%) respectively. Serious infections were 5.6%, 4.9% and 3.9% — no worse on combination therapy.
Written into the record, not signed off as a reviewed claim
CESAME: a fivefold hazard for lymphoproliferative disorder on current thiopurine
In plain words
A French cohort followed nearly twenty thousand people with inflammatory bowel disease. Those currently taking a thiopurine developed lymphoma at about five times the rate of those who never had. Those who had stopped were back near baseline. The absolute numbers are small — about nine cases per ten thousand patient-years — and the ratio is large.
What was measured
Incidence of lymphoproliferative disorder per 1,000 patient-years by thiopurine exposure status, with multivariate adjustment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A prospective nationwide French observational cohort enrolled 19,486 patients with inflammatory bowel disease reported by 680 gastroenterologists, with a median follow-up of 35 months. At baseline 5,867 (30.1%) were receiving thiopurines, 2,809 (14.4%) had discontinued and 10,810 (55.5%) had never received them. Twenty-three lymphoproliferative disorders were diagnosed. Incidence was 0.90 per 1,000 patient-years (95% CI 0.50 to 1.49) in current users, 0.20 (0.02 to 0.72) in past users and 0.26 (0.10 to 0.57) in never-users (P=0.0054). The multivariate-adjusted hazard ratio for current against never use was 5.28 (95% CI 2.01 to 13.9, P=0.0007). Most cases matched the pathological range of post-transplant lymphoproliferative disease, consistent with an Epstein-Barr-driven mechanism.
Written into the record, not signed off as a reviewed claim
PANTHER-IPF: prednisone with azathioprine killed patients with pulmonary fibrosis
In plain words
A steroid plus azathioprine plus an antioxidant had been standard treatment for idiopathic pulmonary fibrosis for years without ever being tested against placebo. When it finally was, the trial stopped that arm early: eight deaths against one, and three times as many hospitalisations.
What was measured
Death and hospitalisation at planned interim analysis, combination therapy against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
PANTHER-IPF randomised patients with idiopathic pulmonary fibrosis and mild-to-moderate lung function impairment to prednisone plus azathioprine plus N-acetylcysteine, to N-acetylcysteine alone, or to placebo. At a planned interim analysis with about half the data collected — 77 patients in the combination group and 78 in the placebo group — the combination arm showed an increased rate of death (8 against 1, P=0.01) and hospitalisation (23 against 7, P<0.001), with no evidence of physiological or clinical benefit. The independent data and safety monitoring board recommended termination of the combination arm at a mean follow-up of 32 weeks.
Written into the record, not signed off as a reviewed claim
Two genes decide who can take it, and the label says so
In plain words
A small proportion of people inherit two broken copies of one of the enzymes that disposes of this drug. In them, a normal dose accumulates until it destroys the bone marrow. Which gene matters depends on ancestry, and the label carries the numbers.
What was measured
Population frequencies of loss-of-function TPMT and NUDT15 alleles, and their association with severe myelosuppression, as stated on the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Azathioprine releases 6-mercaptopurine, which is inactivated by two routes: thiol methylation by thiopurine S-methyltransferase and oxidation by xanthine oxidase, while NUDT15 converts active thioguanine nucleotides to inactive monophosphates. The label states that approximately 0.3% (1 in 300) of patients of European or African ancestry carry two loss-of-function TPMT alleles with little or no activity, and approximately 10% carry one; the TPMT*2, *3A and *3C alleles account for about 95% of reduced-activity individuals. NUDT15 deficiency is found in under 1% of patients of European or African ancestry, but among patients of East Asian ancestry 2% carry two loss-of-function alleles and approximately 21% carry one, most commonly the p.R139C variant. The label states that patients with TPMT or NUDT15 deficiency require alternative therapy or dose modification because of the risk of severe myelosuppression.
Source
IMURAN (azathioprine) tablets United States prescribing information, Clinical Pharmacology and Warnings sections (NDA 016324)
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
A boxed warning for malignancy, on a risk that is hard to separate from the disease
In plain words
The label warns that long-term use raises the risk of cancer, including two specific lymphomas. That warning rests on observational data, and the diseases the drug treats also raise cancer risk on their own. Untangling the two has proved difficult and the field has not fully done it.
What was measured
That the measured lymphoma excess is caused by the drug rather than by the disease it treats — the reversal on discontinuation supports the drug, and the trials that would settle it have not been run
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The IMURAN boxed warning states that chronic immunosuppression with a purine antimetabolite increases the risk of malignancy in humans, and specifically names post-transplant lymphoma and hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. The supporting evidence is observational: transplant registries, and cohorts such as CESAME, which measured an adjusted hazard ratio of 5.28 for lymphoproliferative disorder in current thiopurine users. Confounding by indication and by disease severity is the standing objection — people on thiopurines have more active disease — and the CESAME finding that past users return to near-baseline incidence (0.20 against 0.26 per 1,000 patient-years) is the strongest argument against that objection, since disease severity does not reverse when the drug stops. Hepatosplenic T-cell lymphoma in particular is reported overwhelmingly in young men on combined thiopurine and anti-TNF therapy, which makes attribution to either drug alone unresolvable from case series.
Written into the record, not signed off as a reviewed claim
From first-line immunosuppressant to a drug used because it is cheap
In plain words
For twenty years azathioprine and steroids were the whole of transplant medicine. Cyclosporine displaced it as the main agent in the 1980s, mycophenolate displaced it as the antimetabolite in the 1990s, and the biologics beat it in Crohn’s disease in 2010. It is still used, and the reason has changed from being the best option to being an affordable one.
What was measured
That continued widespread use reflects continued first-line efficacy — each of the three head-to-head comparisons in this batch places it behind the alternative, and the case for it now rests substantially on cost and on familiarity
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Azathioprine was introduced into clinical transplantation in 1962 and, with corticosteroids, constituted standard immunosuppression until cyclosporine arrived in 1983. Mycophenolate mofetil, which inhibits the same de novo purine pathway with selectivity for the type II isoform of inosine monophosphate dehydrogenase expressed preferentially in lymphocytes, replaced it in most kidney transplant protocols after trials in the mid-1990s. In inflammatory bowel disease, SONIC established in 2010 that infliximab alone outperformed azathioprine alone on corticosteroid-free remission (44.4% against 30.0%) and on mucosal healing (30.1% against 16.5%), and AZTEC established in 2013 that early azathioprine did not beat placebo in newly diagnosed disease. The drug remains in wide use, and at US$0.12 a tablet the reason is not obscure.
Written into the record, not signed off as a reviewed claim
The licensed indications are two; the actual uses are a dozen
In plain words
The label covers kidney transplant rejection and rheumatoid arthritis. The drug is used routinely for Crohn’s disease, ulcerative colitis, autoimmune hepatitis, myasthenia gravis, lupus, vasculitis and several skin diseases, none of which is on the label. Some of those have good trial support and some have almost none, and the label does not distinguish.
What was measured
That because the drug is widely used for a condition it is effective for that condition — the licensed indications and the actual indications overlap only partly, and the evidence behind the unlicensed ones ranges from randomised to almost none
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The IMURAN indications section covers adjunctive prevention of rejection in renal homotransplantation and the management of active rheumatoid arthritis in patients who have not responded adequately to rest, aspirin or other non-steroidal anti-inflammatory drugs. Inflammatory bowel disease, autoimmune hepatitis, myasthenia gravis, systemic lupus erythematosus, ANCA-associated vasculitis, bullous pemphigoid and atopic dermatitis are all treated with azathioprine off-label. The evidence quality across those uses is highly uneven: maintenance of remission in ANCA vasculitis and in autoimmune hepatitis has randomised support, while induction of remission in Crohn’s disease does not — Cochrane review evidence and the AZTEC result both point against it. Off-label use is lawful and often appropriate; the audit point is that a reader looking at the label learns nothing about which of these uses is well supported.
Source
IMURAN (azathioprine) tablets United States prescribing information, Indications and Usage section (NDA 016324); Panés J et al., Gastroenterology 2013;145:766-774
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
19 documents were read for this substance.
RNAWiki source record
19 of them state the same halfLife, and they agree.
RNAWiki source record
19 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
MRK240IY2L
CAS registry number
446-86-6
PubChem compound
2265
RxNorm concept
1256
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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
9 approved applications cover products containing this substance. The earliest was NDA016324, approved 19680320 to LEGACY.
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What is not here
7 questions this page could not answer
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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 purine antimetabolite prodrug that starves dividing lymphocytes of the building blocks for DNA — it made kidney transplantation survivable in the 1960s and still prevents rejection, and it failed to beat placebo for sustained corticosteroid-free remission in newly diagnosed Crohn’s disease (44.1% against 36.5%, difference 7.6%, 95% CI -9.2 to 24.4, P=0.48) while carrying a boxed warning for lymphoma and a measured hazard ratio of 5.28 for lymphoproliferative disorder in 19,486 followed patients.
Recorded evidence blocks (10)
Q2
On the Azathioprine label: indicated for what?
"INDICATIONS & USAGE Azathioprine is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms.": indications and usage on Azathioprine's label. DailyMed label · 5116b22b-1460-5535-e063-6394a90acbe5 · 2026-05-05
Q3
119 registered trials of Azathioprine — at which phases?
Registered studies posting no result
93 of 119
119 registered studies of Azathioprine: 36 phase3, 31 phase4, 26 phase2, 13 na, 13 na or unstated, 3 phase1, 2 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
safety (1), accrual/recruitment (14), sponsor decision unspecified (1) and other (7): Azathioprine's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Study design changes were needed based on GIPF-001 results"; 23 of 119 registered studies
Show the evidence
Trial
NCT00052039
terminated; "Study design changes were needed based on GIPF-001 results"
NCT00098111
terminated; "Lack of recruitment"
NCT00113503
terminated; "Insufficient enrollment"
NCT00230035
withdrawn; "Recommended by DSMB due to lack of accrual"
NCT00425438
terminated; "Study was terminated early for administrative reasons."
NCT00504244
terminated; "Insufficient recruitment"
14 further recorded trials
NCT00537316
terminated; "Infusion reactions during re-induction cycles after a period of no treatment in another study \[P04563, NCT0358670\]"
NCT00608894
terminated; "Study was discontinued due to slow enrollment"
NCT00626197
terminated; "Study was terminated due to an imbalance of serious and opportunistic infections in the ocrelizumab treated patients versus the placebo arm."
NCT00796250
terminated; "Due to poor patient recruitment, a decision was made to terminate this trial."
NCT00866684
terminated; "Insufficient patient recruitment"
NCT00984568
terminated; "Due to slow recruitment the study was stopped prematurely."
NCT01275274
withdrawn; "no subject enrolled in nearly 2 years"
NCT01752790
withdrawn; "The study will be part of a European multicenter trial (Infliximab Top-down Study in Kids with Crohn's disease)"
NCT01880307
terminated; "Not enough study subjects"
NCT02247258
terminated; "Slow recruitment"
NCT02281799
withdrawn; "No Participants Enrolled"
NCT02413047
terminated; "physician decision to stop study early due to low enrollment"
NCT02444728
terminated; "Because of insufficient enrollement"
NCT02579733
terminated; "Not enough number of enrolling patient"
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Azathioprine used 50mg azathioprine tablets + 5mg prednisone tablets — over how long?
studies of Azathioprine used the recorded amount. ClinicalTrials.gov · 2026-09-01
3 recorded entries; human; oral; also "50mg azathioprine tablets + 5mg prednisone tablets", "Azathioprine 50Mg Tab", "Azathioprine 10mg/mL oral suspension"
1 to 2 hours; Maximum serum radioactivity occurs at 1 to 2 hours after oral 35 S-azathioprine and decays with a half-life of 5 hours.
metabolismclinical_pharmacology
Because of extensive metabolism, only a fraction of the radioactivity is present as azathioprine.
recorded 2026-05-05 · last checked 2026-09-04
Q7
Which running trial of Azathioprine could settle lifespan?
NCT02081755 measures Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first., reading out 2027-03.
2 open trials; n 336; "Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer"
Show the evidence
Trial
NCT02081755
"Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer"; n 336; "Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first."; 2027-03
NCT07616154
"Haploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease"; n 45; "GVHD-free and rejection free survival (GRFS)"; 2035-09
Q8
Which 30 trials of Azathioprine posted no result?
Posted no result
30 of 30 completed trials
Registrations
NCT00268515, NCT00150891, NCT00753103, NCT00525473, NCT01392833 and NCT00946946, and 24 more
Completion dates
oldest 2003-03; newest 2024-01
Show the evidence
Trial
NCT00268515
2003-03
NCT00150891
2006-01
NCT00753103
2006-07
NCT00525473
2008-01
NCT01392833
2008-01
NCT00946946
2009-07
14 further recorded trials
NCT00626678
2010-09
NCT01381432
2011-05
NCT01390766
2011-05
NCT00204022
2011-08
NCT00521950
2011-12
NCT00748644
2013-06
NCT01056237
2013-06
NCT00355862
2014-05
NCT01564823
2015-01
NCT01112215
2015-12
NCT02645565
2016-12
NCT02949349
2017-01-25
NCT00494741
2017-11-29
NCT07012239
2018-01-01
Q9
At the median, Azathioprine's trials enrolled 86 people — anything larger?
Median enrolment
86
Largest enrolment
2000
Registered trials counted
118
Q10
What do 7080 spontaneous reports say about Azathioprine — 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.
Azathioprine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 7080 reaction mentions were counted: drug intolerance 1181; rheumatoid arthritis 938; treatment failure 902; drug hypersensitivity 751. FAERS via Open Targets · CHEMBL1200400 · 2026-06-24
Show the evidence
drug intolerance
1181
rheumatoid arthritis
938
treatment failure
902
drug hypersensitivity
751
condition aggravated
730
pneumonia
690
4 more recorded rows
hypersensitivity
510
joint swelling
474
leukopenia
464
crohn's disease
440
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Azathioprine's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
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