Crohn’s disease, a chronic inflammatory bowel disease, affects over 1 million people in the United States. Patients with moderate-to-severe Crohn's disease are impacted by frequent and intense abdominal pain and diarrhea, sometimes with significant weight loss. Symptoms can negatively affect physical, emotional, and social well-being. Medications used to treat Crohn's disease include corticosteroids, immunomodulators, and biologics. The goal is to relieve symptoms, improve quality of life, and prevent disease progression.
In today's side-by-side comparison, we compare the latest clinical practice guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA) on pharmacotherapy for moderate-to-severe Crohn’s disease.
Guidelines for Comparison
| Item | ACG Clinical Guideline: Management of Crohn's Disease in Adults | AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease |
|---|---|---|
| Authoring Society | American College of Gastroenterology | American Gastroenterological Association |
| Publication Date | June 2025 | November 2025 |
| Uses GRADE | Yes | Yes |
| Graded Recommendations | Yes | Yes |
| Links | Summary / Full Text | Summary / Full Text |
Key Takeaways
The ACG guideline provides 35 recommendations and 59 key concepts encompassing testing and diagnosis, as well as disease management of mild-to-moderate, moderate-to-severe, severe/fulminant and fistulizing and stricturing Crohn’s disease. There are also recommendations regarding when to refer patients for surgery and post-operative management.
The AGA guideline is more focused with 16 recommendations for medications used to manage moderate-to-severe Crohn’s disease.
Now we will review the similarities and differences in medications recommended for the treatment of moderate-to-severe Crohn’s disease.
Corticosteroids
- The ACG recommends corticosteroids for induction of remission in moderate-to-severe Crohn’s disease.
- The AGA, however, suggests that advanced therapies be initially used instead of corticosteroids and/or immunomodulator monotherapy.
Thiopurines
- Both guidelines recommend against using thiopurines for induction of remission, but suggest that thiopurines may be used for remission maintenance.
Methotrexate
- Both guidelines suggest using methotrexate, administered by either subcutaneous or intramuscular injection.
- What differs in these recommendations is that the ACG recommends this for maintenance of remission while the AGA recommends this for both induction and maintenance therapy.
Anti-TNF Agents
- Adalimumab
- The ACG recommends adalimumab for induction and maintenance of remission.
- The AGA looked at adalimumab monotherapy versus combination therapy with thiopurines or methotrexate and was not able to make a recommendation on superiority of one or the other for induction or maintenance of remission.
- Infliximab
- The ACG recommendations support the use of intravenous infliximab for induction and maintenance of remission with the option of subcutaneous infliximab for maintenance in those who achieved remission with IV infliximab.
- Both guidelines recommend that infliximab be used as combination therapy with thiopurines in patients naive to those agents.
- Certolizumab pegol
- Both guidelines recommend certolizumab pegol for induction and maintenance of remission.
Non-TNF Targeting Biologics
- Both guidelines recommend non-TNF biologics vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab, and upadacitinib for induction and maintenance therapy.
- The AGA identifies using non-TNF targeting biologics in combination therapy as a knowledge gap that needs further investigation before a recommendation for or against can be issued.
Choosing an Advanced Therapy
- Patients Naive to Advanced Therapies
- The AGA recommends patients naive to advanced therapies start treatment with a drug known to be more effective—infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab instead of less effective drugs—certolizumab pegol and upadacitinib.
- The ACG does not make a recommendation favoring use of any one advanced therapy for patients naive to these treatments.
- Patients with Previous Exposure to Advanced Therapies
- For patients with prior exposure to anti-TNF agents who are starting a non-TNF targeting biologic, the ACG recommends upadacitinib and has preference for risankizumab over ustekinumab.
- The AGA recommends using a high efficacy medication—adalimumab, risankizumab, guselkumab, upadacitinib or an intermediate efficacy medication— ustekinumab or mirikizumab over a lower efficacy medication like vedolizumab, certolizumab pegol for patients with prior exposure to advanced therapies, especially anti-TNF agents.
Comparison of Recommendations
| Category | ACG | AGA |
|---|---|---|
| Corticosteroids | We recommend oral corticosteroids for short-term induction of remission in patients with moderately to severely active Crohn's disease. | In adult outpatients with moderate-to-severely active Crohn's disease, the AGA suggests upfront use of advanced therapy compared with step-up therapy with initial use of corticosteroids and/or immunomodulator monotherapy. |
| Thiopurines | We recommend against azathioprine (at doses of 1.5–2.5 mg/kg/d) and 6-mercaptopurine (at doses of 0.75–1.5 mg/kg/d) for induction of remission in moderately to severely active Crohn's disease. We suggest azathioprine (at doses of 1.5–2.5 mg/kg/d) and 6-mercaptopurine (at doses of 0.75–1.5 mg/kg/d) for maintenance of remission in patients with moderately to severely active Crohn's disease who had induction of remission with corticosteroids. | In adult outpatients with moderate-to-severely active Crohn's disease, the AGA suggests against using thiopurines monotherapy over no treatment for inducing remission. In adult outpatients with moderate-to-severely active Crohn's disease who have achieved remission, the AGA suggests using thiopurine monotherapy over no treatment for maintaining remission. |
| Methotrexate | We suggest methotrexate (up to 25 mg once weekly intramuscular or subcutaneous) for maintenance of remission in patients with moderately to severely active Crohn's disease who had induction of remission with corticosteroids. | In adult outpatients with moderate-to-severely active Crohn's disease, the AGA suggests using subcutaneous or intramuscular methotrexate monotherapy over no treatment. In adult outpatients with moderate-to-severely active Crohn's disease, the AGA suggests against using oral methotrexate monotherapy over no treatment. |
| Anti-TNF Agents | We recommend anti-TNF agents (intravenous infliximab, subcutaneous adalimumab, subcutaneous certolizumab pegol) for induction and maintenance of remission for moderately to severely active Crohn's disease. We recommend combination therapy of intravenous infliximab with immunomodulators (thiopurines) as compared with treatment with either immunomodulators alone or intravenous infliximab alone in patients with Crohn's disease who are naive to those agents. We recommend subcutaneous infliximab as an option for maintenance of remission in patients with moderately to severely active Crohn's disease who respond to intravenous induction with infliximab. | In adult outpatients with moderate-to-severely active Crohn's disease, the AGA makes no recommendation on using adalimumab in combination with thiopurines or methotrexate over adalimumab monotherapy. In adult outpatients with moderate-to-severely active Crohn's disease, the AGA suggests the use of certolizumab pegol or vedolizumab, over no treatment. In adult outpatients with moderate-to-severely active Crohn's disease who are naive to thiopurines and starting infliximab, the AGA suggests using infliximab in combination with thiopurines rather than infliximab monotherapy. In adult outpatients with moderate-to-severely active Crohn's disease, the AGA makes no recommendation on using infliximab in combination with methotrexate over infliximab mono therapy. |
| Non-TNF Targeting Biologics | We recommend intravenous vedolizumab for induction and maintenance of symptomatic remission in patients with moderately to severely active Crohn's disease. We recommend subcutaneous vedolizumab as an option for maintenance of remission in patients with moderately to severely active Crohn's disease who respond to two intravenous induction doses of vedolizumab. We recommend ustekinumab in patients with moderate-to-severe Crohn's disease for induction and maintenance of remission. We recommend the use of risankizumab for induction and maintenance of remission in patients with moderate to severely active Crohn's disease. We recommend the use of mirikizumab for induction and maintenance of remission in patients with moderate to severely active Crohn's disease. We recommend the use of intravenous guselkumab for induction followed by subcutaneous guselkumab for maintenance of remission in patients with moderate to severely active Crohn's disease. We recommend the use of subcutaneous guselkumab for induction and maintenance of remission in patients with moderate to severely active Crohn's disease. | Monotherapy: In adult outpatients with moderate-to-severely active Crohn's disease, the AGA recommends the use of infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib, over no treatment. Combination Therapy: In adult outpatients with moderate-to-severely active Crohn's disease, the AGA makes no recommendation in favor of, or against, using non–TNF-targeting biologics (vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) in combination with thiopurines or methotrexate or corresponding biologic monotherapy. |
| Advanced Therapy Choice | We recommend the use of risankizumab as compared with ustekinumab in patients with moderate-to-severe Crohn's disease and prior exposure to anti-TNF therapy. We recommend upadacitinib for induction and maintenance of remission for patients with moderately to severely Crohn's disease who have previously been exposed to anti-TNF agents. | In adult outpatients with moderate-to-severely active Crohn's disease who are naive to advanced therapies, the AGA suggests using a higher efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab), rather than a lower efficacy medication (certolizumab pegol, upadacitinib). In adult outpatients with moderate-to-severely active Crohn's disease who have previously been exposed to 1 or more advanced therapies, particularly TNF antagonists, the AGA suggests using a higher efficacy medication (adalimumab, risankizumab, guselkumab, upadacitinib) or an intermediate efficacy medication (ustekinumab, mirikizumab), rather than a lower efficacy medication (vedolizumab, certolizumab pegol). |
This concludes our side-by-side comparison on pharmacotherapy for moderate-to-severe Crohn’s disease. Don’t forget to sign up for alerts to stay informed on the latest published guidelines and articles.
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