Aminosalicylates (5-ASA)

Aminosalicylates (5-ASA), such as mesalamine, are anti-inflammatory medicines used mainly for mild to moderate ulcerative colitis. They calm inflammation directly in the colon lining and have a long track record of safety. This article explains how 5-ASA drugs work, when they are helpful, common side effects, and how they fit alongside other IBD treatments.

Key takeaways

• 5-ASA medicines are first-line treatment for mild to moderate ulcerative colitis. (crohnscolitisfoundation.org)

• They work best when targeted to the inflamed area, often by combining oral and rectal forms. (pmc.ncbi.nlm.nih.gov)

• They are not strong immunosuppressants and usually have a favorable long-term safety profile. (crohnscolitisfoundation.org)

• Kidney injury and acute “5-ASA intolerance” are rare but important risks, so regular blood tests are recommended. (pmc.ncbi.nlm.nih.gov)

• 5-ASA has a limited role in Crohn’s disease and is often stopped once effective biologic or small-molecule therapy is in place. (journals.lww.com)

What are aminosalicylates (5-ASA)?

Aminosalicylates are medicines that contain 5‑aminosalicylic acid (5‑ASA). They act locally on the inner lining of the gut to reduce inflammation, mainly in the colon and rectum. (crohnscolitisfoundation.org)

They are a cornerstone treatment for mild to moderate ulcerative colitis (UC), both to bring flares under control and to help keep remission. Guidelines from major societies recommend oral and/or rectal 5‑ASA as first-line therapy for this group. (pmc.ncbi.nlm.nih.gov)

Unlike corticosteroids or many biologics, 5‑ASA medicines are not broad immunosuppressants. They mainly damp down inflammatory signals in the gut wall, which is why infection and cancer risks are not clearly increased in the same way as with stronger immunosuppressive drugs. (crohnscolitisfoundation.org)

Types and formulations

Several related 5‑ASA drugs are used in practice:

Mesalamine is also available as suppositories, foams, and enemas. For disease limited to the rectum (proctitis) or rectum plus sigmoid colon, guidelines strongly favor rectal 5‑ASA, often in combination with oral therapy for more extensive disease. (gastro.org)

When are 5-ASA medicines used in ulcerative colitis?

In UC, 5‑ASA drugs are primarily used in two settings:

• Induction of remission in mild to moderate disease

• Maintenance of remission after symptoms and inflammation have improved

For mild ulcerative proctitis, rectal mesalamine alone is usually recommended for both induction and maintenance. (pmc.ncbi.nlm.nih.gov)

For left‑sided or extensive mild–moderate UC, guidelines support: (pmc.ncbi.nlm.nih.gov)

• Oral mesalamine or a diazo‑bonded 5‑ASA as baseline therapy

• Adding rectal mesalamine (suppository or enema) to increase remission rates

• Using standard or higher oral doses if symptoms do not respond to initial treatment

In moderate to severe UC or acute severe colitis, 5‑ASA alone is usually not enough. Corticosteroids, biologics, or small-molecule drugs become the main therapies, and 5‑ASA may be stopped in many of these patients. (gastro.org)

How well do 5-ASA medicines work?

For mild to moderate UC, oral and rectal 5‑ASA clearly outperform placebo for both inducing and maintaining remission. A large meta‑analysis found that oral 5‑ASA cut the risk of relapse by about one third compared with no treatment, with standard doses more effective than very low doses. (journals.lww.com)

Combining oral plus rectal mesalamine works better than either alone for many people with left‑sided or extensive disease. (pmc.ncbi.nlm.nih.gov) Clinical trials of modern mesalamine formulations show high remission rates over 6 to 24 weeks, and once‑daily dosing maintains remission as well as divided doses. (pubmed.ncbi.nlm.nih.gov)

Symptom improvement is often seen within 2 to 4 weeks, though some patients improve more slowly. (pubmed.ncbi.nlm.nih.gov)

Safety, side effects, and monitoring

Overall, 5‑ASA medicines are well tolerated. Common side effects are usually mild and can include: (crohnscolitisfoundation.org)

• Headache

• Nausea, heartburn, or mild stomach pain

• Gas or diarrhea

• Joint or muscle aches

• Mild rash or flu‑like symptoms

A small number of patients develop acute 5‑ASA intolerance, which can mimic a severe flare. Typical features are worsening diarrhea, abdominal pain, fever, and increased rectal bleeding soon after starting or increasing 5‑ASA. Symptoms usually improve when the drug is stopped, and an alternative class is often needed. (pmc.ncbi.nlm.nih.gov)

A key rare risk is kidney injury, especially interstitial nephritis. Renal dysfunction has been reported in about 1% of patients on 5‑ASA, with biopsy‑proven interstitial nephritis in roughly 0.2%. (pmc.ncbi.nlm.nih.gov) Because damage can appear months or years after starting therapy, professional societies and national formularies advise: (pmc.ncbi.nlm.nih.gov)

• Checking kidney function (creatinine or eGFR) before starting

• Rechecking at about 2–3 months

• Ongoing checks at least yearly, more often if kidney function is impaired

Other rare but important adverse effects include pancreatitis, liver inflammation, blood count changes, inflammation of the heart (myocarditis), and serious skin reactions such as Stevens–Johnson syndrome. (crohnscolitisfoundation.org)

Sulfasalazine‑specific issues include sulfa allergy, bone marrow suppression, liver toxicity, and reversible low sperm counts, as well as reduced folate levels. Folate supplementation is commonly used when sulfasalazine is prescribed. (pubmed.ncbi.nlm.nih.gov)

Special situations: Crohn’s disease, pregnancy, and long-term use

Role in Crohn’s disease

Older studies suggested limited benefit of mesalamine in Crohn’s disease, and more recent guidelines recommend against using oral mesalamine for most Crohn’s induction or maintenance. Sulfasalazine may be considered only for mild colonic Crohn’s. (journals.lww.com)

For patients who escalate to biologics or thiopurines, several large cohort and cost‑effectiveness studies show no added benefit from continuing 5‑ASA, while pill burden and cost increase. (pubmed.ncbi.nlm.nih.gov)

Pregnancy and breastfeeding

European consensus statements classify mesalamine and sulfasalazine as low risk in pregnancy and lactation. (academic.oup.com) Maintaining remission during pregnancy is strongly associated with better outcomes for both parent and baby, so effective maintenance therapy is usually continued.

Sulfasalazine can reduce folate levels, so higher-dose folic acid is often recommended before conception and during pregnancy when this drug is used. (academic.oup.com)

Long-term strategy

Many people remain on 5‑ASA for years. Long-term studies and guidelines support 5‑ASA as the standard maintenance option in previously mild UC, as it clearly reduces relapse risk and allows steroid‑free control. (journals.lww.com)

In patients whose disease has required advanced therapies, clinicians increasingly simplify regimens by stopping 5‑ASA once the more potent drug is working, especially if the original disease was moderate to severe. (guidelinecentral.com)

FAQs

Are 5-ASA medicines considered “immunosuppressants”?

5‑ASA drugs reduce inflammation mainly on the surface of the colon rather than broadly suppressing the immune system. They are not associated with the same infection or cancer risks seen with systemic immunosuppressants such as steroids, thiopurines, or biologics. (crohnscolitisfoundation.org)

How long does it usually take 5-ASA to start working?

Clinical trials of modern mesalamine formulations show that rectal bleeding often improves within about 2 weeks, and stool frequency within 4–6 weeks for many patients. (pubmed.ncbi.nlm.nih.gov) Some people respond faster and others more slowly, so care teams usually judge response over several weeks rather than days.

What blood tests are recommended while on 5-ASA?

Most guidance suggests checking kidney function before starting, again after a few months, and then at least once a year, with more frequent tests in anyone with kidney impairment. (pmc.ncbi.nlm.nih.gov) Many clinicians also periodically monitor liver tests and complete blood counts, especially if sulfasalazine is used.

Why might a doctor stop 5-ASA when starting a biologic or JAK inhibitor?

For patients who need biologics or small‑molecule drugs because UC is moderate or severe, studies show that continuing 5‑ASA alongside these stronger therapies usually does not improve outcomes but does add cost and pill burden. (pubmed.ncbi.nlm.nih.gov) In that setting, many teams choose to rely on the more potent medication alone while continuing close monitoring of disease control.