Table 1.
Summary of Consensus Recommendations for the Management of Pediatric Crohn’s Diseasea
| Aminosalicylates |
| Recommendation 1: In patients with moderate CD, we recommend against the use of 5-ASAs to induce clinical remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 67%; agree, 33%. |
| Recommendation 2: In patients with moderate CD limited to the colon, we suggest against the use of sulfasalazine to induce clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 67%; agree, 20%; neutral, 7%; disagree, 0%; strongly disagree, 7%. |
| Recommendation 3: In patients with CD in clinical remission, we recommend against sulfasalazine or 5-aminosalicylic acid to maintain clinical remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 33%; agree, 47%; neutral, 20%. |
|
Budesonide
Recommendation 4: In patients with mild to moderate ileal and/or right colonic CD, we suggest oral controlled ileal release budesonide to induce clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 33%; agree, 67%. |
| Recommendation 5: In patients with CD, we recommend against oral controlled ileal release budesonide to maintain clinical remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 87%; agree, 13%. |
| Corticosteroids |
| Recommendation 6: In patients with moderate to severe CD, we suggest conventional corticosteroids (eg, prednisone) to induce clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 47%; agree, 53%. |
| Recommendation 7: In patients with mild to moderate active CD despite use of sulfasalazine, 5-ASA, oral budesonide, or exclusive enteral nutrition, we suggest oral prednisone to induce clinical remission. |
| GRADE: Conditional recommendation, moderate-quality evidence. |
| Vote: strongly agree, 33%; agree, 67%. |
| Recommendation 8: In patients with CD of any severity, we recommend against oral corticosteroids to maintain clinical remission. |
| GRADE: Strong recommendation, low-quality evidence. |
| Vote: strongly agree, 100%. |
| Exclusive enteral nutrition |
| Recommendation 9: In patients with CD, we suggest exclusive enteral nutrition to induce clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence (for pediatrics). |
| Vote: strongly agree, 33%; agree, 67%. |
| Recommendation 10: In patients with CD, we recommend against partial enteral nutrition to induce clinical remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 80%; agree, 20%. |
| Recommendation 11: In patients with CD in remission, we suggest that if partial enteral nutrition is used it should be combined with other medications to maintain clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 13%; agree, 87%. |
| Immunosuppressants |
| Recommendation 12: In patients with CD of any severity, we recommend against thiopurine monotherapy to induce clinical remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 87%; agree, 13%. |
| Recommendation 13: In female patients with CD we suggest a thiopurine to maintain remission. |
| GRADE: Conditional recommendation, low-quality evidence. |
| Vote: strongly agree, 20%; agree, 73%; neutral, 7%. |
| Recommendation 14: In patients with CD, we suggest that testing for TPMT by genotype or enzymatic activity be done prior to initiating thiopurine therapy to guide dosing. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 27%; agree, 67%; neutral, 7%. |
| Recommendation 15: In patients with CD we suggest parenteral methotrexate to maintain clinical remission. |
| GRADE: Conditional recommendation, low-quality evidence. |
| Vote: strongly agree, 40%; agree, 60%. |
| Recommendation 16: In patients with CD who are in clinical remission with a thiopurine or methotrexate as maintenance therapy, we suggest assessment for mucosal healing within the first year to determine the need to modify therapy if significant ulcerations persist. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 13%; agree, 80%; neutral, 7%. |
| Anti-TNF biologic therapies |
| Recommendation 17: In patients with moderate to severe inflammatory CD who have failed to achieve clinical remission with corticosteroids, we recommend anti-TNF therapy (adalimumab, infliximab) to induce and maintain clinical remission. |
| GRADE: Strong recommendation, high-quality evidence. |
| Vote: strongly agree, 100%. |
| Recommendation 18: In patients with moderate to severe inflammatory CD who fail to achieve or maintain clinical remission with a thiopurine or methotrexate, we recommend anti-TNF therapy to induce and maintain clinical remission. |
| GRADE: Strong recommendation, high-quality evidence. |
| Vote: strongly agree, 93%; agree, 7%. |
| Recommendation 19: In patients with severe inflammatory CD judged at risk for progressive, disabling disease, we suggest anti-TNF therapy as first-line therapy to induce and maintain clinical remission. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 47%; agree, 53%. |
| Recommendation 20: When starting infliximab in males, we suggest against using it in combination with a thiopurine. |
| GRADE: Conditional recommendation, low-quality evidence. |
| Vote: strongly agree, 40%; agree, 47%; neutral, 13%. |
| Recommendation 21: When starting adalimumab in males, we suggest against using it in combination with a thiopurine. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 40%; agree, 53%; neutral, 7%. |
| Recommendation 22: In male patients with CD receiving immunomodulator therapy in combination with an anti-TNF therapy, we suggest methotrexate in preference to thiopurines. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 27%; agree, 53%; neutral, 20%. |
| Recommendation 23: In patients with CD who have a suboptimal clinical response to anti-TNF induction therapy or loss of response to maintenance therapy, we suggest regimen intensification informed by therapeutic drug monitoring. |
| GRADE: Conditional recommendation, very-low-quality evidence. |
| Vote: strongly agree, 53%; agree, 47%. |
| Non–anti-TNF biologic therapies |
| Recommendation 24: In patients with moderate to severe CD who fail to achieve or maintain clinical remission with anti-TNF–based therapy, we suggest ustekinumab to induce and maintain clinical remission. |
| GRADE: Conditional recommendation, moderate-quality evidence for induction, low-quality evidence for maintenance. |
| Vote: strongly agree, 47%; agree, 53% |
| Alternative therapies |
| Recommendation 25: In patients with CD, we recommend against cannabis or derivatives to induce or maintain remission. |
| GRADE: Strong recommendation, very-low-quality evidence. |
| Vote: strongly agree, 87%; agree, 7%; neutral, 7%. |
| Statements with no recommendations |
| No consensus A: In patients with mild CD, the consensus group does not make a recommendation (for or against) regarding the use of 5-ASAs to induce clinical remission. |
| No consensus B: In patients with mild CD limited to the colon, the consensus group does not make a recommendation (for or against) regarding the use sulfasalazine to induce clinical remission. |
| No consensus C: In patients with mild CD who have achieved clinical remission with sulfasalazine or 5-ASA, the consensus group does not make a recommendation (for or against) regarding continuing sulfasalazine or 5-ASA to maintain clinical remission. |
| No consensus D: In patients with mild to moderate CD, the consensus group does not make a recommendation (for or against) regarding the use of antibiotics to induce clinical remission. |
| No consensus E: In patients with mild to moderate CD, the consensus group does not make a recommendation (for or against) regarding the use of antibiotics to maintain clinical remission. |
| No consensus F: In male patients with CD the consensus group does not make a recommendation (for or against) regarding a thiopurine to maintain remission. |
| No consensus G: In patients with mild to moderate CD, the consensus group does not make a recommendation (for or against) regarding methotrexate monotherapy to induce clinical remission. |
| No consensus H: In patients with CD, the consensus group does not make a recommendation (for or against) regarding oral methotrexate to maintain clinical remission. |
| No consensus I: In patients with moderate to severe inflammatory CD who have achieved clinical remission but not mucosal healing with a corticosteroid, thiopurine, or methotrexate, the consensus group does not make a recommendation (for or against) regarding anti-TNF therapy to induce and maintain mucosal healing. |
| No consensus J: When starting infliximab in females, the consensus group does not make a recommendation (for or against) regarding combining it with a thiopurine to maintain a durable clinical remission. |
| No consensus K: When starting adalimumab in females, the consensus group does not make a recommendation (for or against) regarding combining it with a thiopurine to maintain a durable clinical remission. |
| No consensus L: In patients with CD who have achieved a clinical remission with anti-TNF therapy, the consensus group does not make a recommendation (for or against) regarding assessment for mucosal healing within the first year to determine the need to modify therapy. |
| No consensus M: In patients with moderate to severe CD who fail to achieve or maintain clinical remission with an anti-TNF–based therapy, the consensus group does not make a recommendation (for or against) regarding the use vedolizumab to induce and maintain clinical remission. |
a The strength of each recommendation was assigned by the consensus group, per the GRADE system, as strong (“we recommend...”) or conditional (“we suggest...”). A recommendation could be classified as strong despite low-quality evidence to support it, or conditional despite the existence of high-quality evidence due to the 4 components considered in each recommendation (risk to benefit balance, patients’ values and preferences, cost and resource allocation, and quality of evidence).