What medications are available in Indonesia for a patient with moderate to severe Inflammatory Bowel Disease (IBD) who cannot tolerate corticosteroids?

Medications Available in Indonesia for Moderate to Severe IBD with Corticosteroid Intolerance

For patients with moderate to severe IBD who cannot tolerate corticosteroids, azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.25 mg/kg/day) should be initiated as first-line therapy, with anti-TNF agents (infliximab or adalimumab) reserved for patients who fail or cannot tolerate thiopurines. 1

First-Line Immunomodulator Therapy

Azathioprine or mercaptopurine are the recommended first-line agents for steroid-refractory or steroid-intolerant disease:

• Azathioprine 1.5-2.5 mg/kg/day is the primary choice based on Grade A evidence from the European Crohn's and Colitis Organisation 1
• Mercaptopurine 0.75-1.25 mg/kg/day is an equivalent alternative 1
• These agents are effective for both Crohn's disease and ulcerative colitis in maintaining remission after steroid-induced remission 2, 3
• Allow 3-4 months for therapeutic response before declaring treatment failure, as thiopurines require prolonged time to reach steady-state 6-thioguanine nucleotide levels 3

Critical Monitoring Requirements

• Check complete blood count within 4 weeks of starting therapy and every 6-12 weeks thereafter to detect neutropenia 1
• Folic acid 5 mg once weekly (taken 3 days after methotrexate if using methotrexate) may reduce side effects 1

Second-Line Anti-TNF Therapy

If thiopurines fail or are not tolerated, infliximab should be initiated:

• Infliximab 5 mg/kg IV at weeks 0,2, and 6 for induction, followed by maintenance every 8 weeks 4
• This is indicated for moderate-to-severe disease refractory to or intolerant of steroids, mesalazine, and thiopurines 1
• Combination therapy with azathioprine or mercaptopurine when initiating infliximab is recommended to prevent antibody formation and improve outcomes 1
• For ulcerative colitis specifically, infliximab is strongly recommended to induce and maintain complete corticosteroid-free remission in steroid-dependent patients 5

Alternative Anti-TNF Options

• Adalimumab is equally effective for moderate to severe Crohn's disease 5
• Golimumab has high-quality evidence for maintaining remission in ulcerative colitis 5
• Evaluate response to anti-TNF induction therapy at 8-12 weeks to determine need for therapy modification 5

Alternative Immunomodulator: Methotrexate

For Crohn's disease patients who are intolerant or non-responders to thiopurines:

• Methotrexate 25 mg IM weekly for up to 16 weeks, followed by 15 mg weekly for maintenance 1
• This has Grade A evidence for chronic active Crohn's disease 1
• Evidence for methotrexate in ulcerative colitis is insufficient and it is not recommended for UC 1, 2

Vedolizumab for Anti-TNF Failures

For patients who fail anti-TNF therapy:

• Primary failure to anti-TNF: Switch to vedolizumab over switching to another anti-TNF 5
• Secondary failure to anti-TNF: Switch to another anti-TNF or vedolizumab based on therapeutic drug monitoring results 5
• Vedolizumab is recommended for moderate to severe active UC that fails corticosteroids, thiopurines, or anti-TNF therapies (moderate-quality evidence) 5
• Evaluate response to vedolizumab at 8-14 weeks 5

What NOT to Use

Mesalazine (5-ASA) is ineffective for patients who have needed steroids:

• Mesalazine has limited benefit in Crohn's disease maintenance, particularly at doses <2 g/day 1
• It is ineffective for patients who required steroids to induce remission (Grade A evidence) 1
• For ulcerative colitis beyond proctitis, oral 5-ASA 2.0-4.8 g/day can be used only for mild to moderate disease as first-line therapy, not for steroid-refractory cases 5

Cost-Effective Maintenance Strategy

For resource-limited settings like Indonesia:

• After achieving remission with infliximab induction (weeks 0,2,6), maintenance with azathioprine plus 5-ASA combination can sustain corticosteroid-free remission in 68% at 1 year and 59% at 2 years 6
• This strategy is cheaper by US$4,526 annually per patient compared to continuing infliximab maintenance 6
• Most relapses (67%) occur within the first 2 years and typically respond to repeat corticosteroid courses 6

Critical Safety Warnings

Serious infections and malignancy risks with anti-TNF therapy:

• Screen for latent tuberculosis before initiating infliximab; treat latent infection prior to use 4
• Monitor for invasive fungal infections (histoplasmosis, coccidioidomycosis, aspergillosis) 4
• Hepatosplenic T-cell lymphoma risk is highest in adolescent and young adult males receiving TNF-blockers with concomitant azathioprine or mercaptopurine 4
• Long-term azathioprine carries risks of myelosuppression and malignancy, though malignancy risk with monotherapy appears not increased relative to general population 3