Aminosalicylates, steroids and immunomodulators in IBD

01Purpose and principlesWhat the treatment does and how it fits into care.

Conventional therapy is chosen by disease, extent, severity and intended phase. Mesalazine acts topically within the colonic lumen and is central to UC; delivery site depends on preparation, so brand and formulation matter. Corticosteroids act quickly enough for induction but cumulative adverse effects make a clear stop plan essential. Budesonide preparations have different release sites and cannot be interchanged casually: an ileal-release product and a colonic multimatrix product answer different anatomical questions. The safest steroid course is the one supported by an effective maintenance strategy.

Thiopurines and methotrexate suppress immune activity slowly. They require pretreatment assessment, reliable shared monitoring and patient education about infection, cytopenia, liver injury and pregnancy. TPMT testing reduces but does not eliminate thiopurine myelotoxicity, while NUDT15 variation may be relevant according to ancestry and local practice. Thiopurine pancreatitis is not predicted by routine metabolite testing and usually precludes rechallenge. Methotrexate safety depends on weekly prescribing, folate, renal awareness and avoidance of interacting drugs. Treatment choice should account for prior malignancy, EBV status, age and combination-biologic risk through specialist discussion.

Key points

Mesalazine is effective for inducing and maintaining mild to moderate ulcerative colitis when formulation and route match extent; it has little general role in active Crohn disease.
Rectal 5-ASA is an active treatment, not an optional extra, for proctitis and left-sided disease; combined oral and topical delivery can outperform either route alone.
Systemic and locally acting corticosteroids induce remission but do not maintain it; steroid dependence, excess or refractoriness is a treatment outcome that demands a new strategy.
Thiopurines have a delayed onset and are maintenance or steroid-sparing medicines, not rapid induction monotherapy; assess TPMT and individual toxicity factors before use.
Methotrexate is prescribed once weekly, with folate and strict pregnancy prevention; daily administration is a potentially fatal medication error.
Baseline and early blood monitoring is more frequent than stable maintenance monitoring, and a downward trend can be clinically important before a numerical stop threshold is reached.
Before immunomodulation review vaccination, active or latent infection risk, cervical screening, skin protection, malignancy history, pregnancy plans, interactions and who owns monitoring.
If objective disease remains active despite adequate exposure, do not prolong toxicity through indefinite dose escalation; consider advanced therapy, nutrition, endoscopy or surgery.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Steroid dependence

Relapse during dose reduction, recurrence soon after stopping or repeated annual courses means the maintenance plan is failing even if each course produces temporary improvement.

Mesalazine intolerance

Headache, gastrointestinal worsening, rash, pancreatitis, chest symptoms or renal change can occur; an acute intolerance syndrome may resemble the UC flare being treated.

Thiopurine marrow toxicity

Sore throat, fever, mouth ulcers, bruising or falling white cells can signal myelosuppression and requires urgent blood testing and specialist advice.

Thiopurine pancreatitis

New persistent epigastric pain and vomiting soon after initiation requires drug cessation and pancreatitis assessment; dose reduction is not a safe assumption.

Methotrexate toxicity

Mucositis, bruising, infection, cytopenia, liver-test abnormality or new respiratory symptoms should prompt immediate review of dose timing, renal function and interacting medicines.

Adrenal suppression

Fatigue, hypotension, nausea or weakness during or after prolonged steroid exposure can indicate adrenal insufficiency, especially during intercurrent illness or abrupt withdrawal.

Red flags requiring action

Fever, sepsis physiology, severe sore throat, spontaneous bleeding or mouth ulceration on thiopurine or methotrexate needs urgent blood count and infection assessment before another dose.
A methotrexate prescription written or taken daily rather than weekly is an emergency medication-safety incident requiring immediate specialist and toxicology advice.
New dyspnoea or diffuse lung infiltrates on methotrexate needs urgent evaluation for infection and drug-related pneumonitis.
Severe epigastric pain after thiopurine initiation suggests pancreatitis and should not be managed by continuing at a lower dose without assessment.
Do not abruptly stop prolonged systemic corticosteroid during acute illness without considering adrenal suppression and providing appropriate medical review.

03Assessment before treatmentTests and checks that guide safe selection.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Baseline full blood count, liver and renal profileFirst step
Why
Identify contraindications and create a safety comparator before conventional immunomodulation.
Interpretation and limitations
Cytopenia, transaminitis or renal impairment changes agent choice and monitoring; repeat abnormalities and trends rather than assuming they are IBD itself.
02
TPMT assay
Why
Estimate thiopurine methylation capacity before azathioprine or mercaptopurine.
Interpretation and limitations
Absent activity usually precludes standard thiopurine use and reduced activity requires specialist modification, but normal activity does not remove the need for serial blood counts.
03
Thiopurine metabolites
Why
Investigate selected non-response, adherence, hypermethylation or toxicity.
Interpretation and limitations
Therapeutic, low or disproportionately methylated patterns can guide specialist optimisation; they do not screen reliably for pancreatitis or replace routine safety bloods.
04
Mesalazine renal monitoring
Why
Detect uncommon but important interstitial nephritis or worsening kidney function.
Interpretation and limitations
Check before treatment and at product- and risk-appropriate intervals; more frequent review is appropriate with renal impairment or a concerning decline.
05
Bone and metabolic assessment
Why
Identify consequences of recurrent or prolonged systemic corticosteroid exposure.
Interpretation and limitations
Review blood pressure, glucose, weight, fracture risk, vitamin D, bone protection and adrenal risk according to dose, duration and cumulative exposure.
06
Pregnancy and reproductive review
Why
Prevent teratogenic exposure and align treatment with conception or breastfeeding plans.
Interpretation and limitations
Methotrexate is contraindicated around conception and pregnancy; obtain current specialist advice because cessation intervals and safety of other IBD medicines differ.

04Treatment approachPreparation, options, escalation and aftercare.

015-ASAOptimise aminosalicylate treatmentFirst stepFirst lineMild to moderate ulcerative colitis is suitable for a mucosal first-line strategy.

1Map proctitis, left-sided or extensive disease and choose suppository, enema and oral delivery that physically reaches the inflamed segment.
2Explain formulation, daily routine and adherence, obtain baseline renal function and check for salicylate, sulfasalazine or excipient-specific risk.
3EscalationAssess response within the agreed induction period, verifying use before declaring failure and adding corticosteroid or escalation when optimised therapy is insufficient.
4Continue effective maintenance at the simplest supported schedule, with renal surveillance and rapid assessment of suspected intolerance or flare.

02STEROIDUse induction without creating dependenceFirst lineObjective activity needs faster control than optimised first-line or maintenance therapy provides.

1Exclude infection and abscess, select topical, ileal-release, colonic-release, oral or intravenous corticosteroid according to anatomy and severity.
2Before prescribing, define dose schedule, taper, adverse-effect prevention and the response point at which treatment will be considered inadequate.
3Start or optimise a steroid-sparing maintenance strategy during induction rather than waiting for another relapse after taper.
4EscalationRecord cumulative exposure and escalate to the IBD team when response is incomplete, taper fails or another course is requested.

03THIOPURINEInitiate slow-onset maintenance safelyA thiopurine is selected for maintenance, combination therapy or steroid-sparing control.

1Review TPMT, full blood count, liver and renal function, infection and vaccination status, cervical screening, EBV context, skin risk, interactions and pregnancy plans.
2Use weight- and enzyme-informed specialist prescribing, explaining delayed benefit and symptoms of marrow, liver, pancreatic and infective toxicity.
3Follow the gastroenterology blood-monitoring schedule closely after initiation and dose changes, responding to trends and symptoms rather than waiting for profound abnormalities.
4Once stable, continue defined shared-care monitoring and review ongoing need, objective disease control and age-related malignancy risk at least annually.

04METHOTREXATEProtect a weekly high-risk prescriptionMethotrexate is chosen as a specialist Crohn disease maintenance or steroid-sparing option.

1Confirm a single named weekly administration day, folate plan, baseline bloods, pregnancy prevention, alcohol discussion, lung history and medicine interaction review.
2Use route and specialist regimen appropriate to evidence and tolerance, ensuring every prescription and patient record states weekly rather than daily.
3Monitor blood count, liver and renal function frequently after initiation and dose change, then at the stable interval defined by the shared protocol.
4Withhold and seek advice for significant infection, mucositis, cytopenia, liver injury, renal decline or pulmonary symptoms, and never compensate a missed dose by doubling.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

Treats mild to moderate UC and maintains remission through direct colonic mucosal exposure.

Mesalazine

Preparation-specific oral or rectal induction followed by a licensed maintenance regimen.

Baseline and ongoing renal review is required; rare nephritis, pancreatitis, blood dyscrasia or intolerance can mimic relapse, and switching formulations needs dose and release-site checking.

Suppresses active inflammation rapidly while a durable maintenance treatment takes effect.

Prednisolone or budesonide formulation

Time-limited induction course with formulation, taper and duration specified explicitly.

Not for maintenance; infection, mood, glucose, blood pressure, bone, ocular and adrenal effects increase with cumulative exposure, while budesonide products target different bowel regions.

Provides slow-onset steroid-sparing maintenance and can reduce immunogenicity with selected biologics.

Azathioprine or mercaptopurine

Specialist weight- and TPMT-informed daily regimen adjusted for toxicity and metabolites.

Myelosuppression, infection, hepatotoxicity, pancreatitis, non-melanoma skin cancer and lymphoma require counselling, monitoring and individual age, EBV and combination-therapy risk assessment.

Offers steroid-sparing maintenance for selected Crohn disease when thiopurines are unsuitable.

Methotrexate

Once-weekly specialist regimen with separately scheduled folic acid and documented administration day.

Daily dosing can be fatal; pregnancy, liver disease, renal impairment, marrow suppression, pulmonary toxicity and interactions including trimethoprim or co-trimoxazole require strict safeguards.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

For mesalazine, document baseline renal function and follow the current product, SPS and local schedule, increasing frequency when renal risk or decline is present.
For corticosteroids, track cumulative courses, glucose, blood pressure, weight, mood, infection, fracture and adrenal risk, not merely the current daily dose.
For thiopurines, follow blood count, liver and renal testing closely after starting and dose changes, then continue stable shared-care monitoring without gaps.
For methotrexate, reconcile the weekly day at every transition, monitor blood, liver and renal profiles, and review new antibiotics or over-the-counter NSAIDs for interactions.
For every immunomodulator, review vaccination, infection history, cervical screening, sun protection, skin lesions, pregnancy plans and objective IBD control.
Create an explicit ownership plan between IBD service, primary care and pharmacy so abnormal results are acted on rather than merely filed.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

Formulation carries anatomy

Mesalazine and budesonide products release at different gastrointestinal sites. Prescribing a class name without checking formulation can miss the diseased segment.

Normal TPMT is not immunity

TPMT reduces a predictable component of thiopurine risk but cannot prevent infection, pancreatitis, hepatotoxicity or later marrow suppression.

Taper failure is data

Symptoms returning as corticosteroid falls indicate unresolved inflammation or an alternative steroid-responsive problem and should trigger objective reassessment, not automatic continuation.

Weekly must be visible

Methotrexate safety improves when the administration day appears on prescriptions, medicine lists, monitoring records and patient-held information at every care transition.

Monitoring needs a responder

A scheduled blood test is not a safety system unless someone is responsible for reviewing it, contacting the patient and changing the prescription.

08Common pitfallsFrequent interpretation and management errors.

01
Using mesalazine as general induction therapy for moderate or severe Crohn disease despite poor evidence for that role.
02
Ignoring rectal 5-ASA in active proctitis and repeatedly increasing oral treatment that does not adequately reach the site.
03
Treating corticosteroid response as durable remission without establishing maintenance before taper.
04
Starting azathioprine as sole rapid induction and labelling it ineffective before its delayed onset could occur.
05
Reassuring from normal TPMT and omitting serial blood monitoring.
06
Entering methotrexate as a daily medicine in prescribing or discharge systems.
07
Continuing a toxic immunomodulator because a metabolite value appears therapeutic despite concerning symptoms or falling blood counts.