Is Xeljanz (tofacitinib) effective for treating Crohn's disease?

Xeljanz (Tofacitinib) Is Not Recommended for Crohn's Disease

Xeljanz (tofacitinib) is not recommended for the treatment of Crohn's disease as it failed to demonstrate significant efficacy in clinical trials and is not approved for this indication.

Evidence on Tofacitinib for Crohn's Disease

Clinical Trial Results

Phase IIb randomized placebo-controlled trials specifically evaluating tofacitinib for Crohn's disease showed disappointing results:

• Tofacitinib failed to meet primary efficacy endpoints in Crohn's disease clinical trials 1
• At week 8 of induction therapy, clinical remission rates were 43.5% with 5 mg twice daily and 43.0% with 10 mg twice daily, compared to 36.7% with placebo - differences that were not statistically significant (p=0.325 and p=0.392) 1
• During the maintenance phase (week 26), clinical response or remission was achieved in 55.8% with 10 mg twice daily versus 38.1% with placebo (p=0.130), again not reaching statistical significance 1
• The clinical development of tofacitinib was subsequently discontinued for Crohn's disease 2

Safety Considerations

While tofacitinib has been approved for ulcerative colitis, its safety profile raises concerns:

• In real-world studies of ulcerative colitis patients, a relatively high rate of adverse events was observed, with 6% of patients discontinuing due to adverse events 3
• Tofacitinib treatment is associated with significant increases in cholesterol, HDL, and LDL levels (18%, 18%, and 21% respectively) 3
• The risk for malignancy and infections may be higher when JAK inhibitors are combined with thiopurines 4

Current Guideline Recommendations for Crohn's Disease

According to established guidelines, the following treatments are recommended for Crohn's disease:

First-line and Established Therapies

• Azathioprine (1.5–2.5 mg/kg/day) or mercaptopurine (0.75–1.5 mg/kg/day) are effective for maintenance therapy and steroid-dependent disease 4
• Methotrexate (15–25 mg IM weekly) is effective for patients who have failed or are intolerant to azathioprine/mercaptopurine 4
• Infliximab (5 mg/kg at 0,2, and 6 weeks, then every 8 weeks) is recommended for patients with refractory disease, particularly for fistulating disease 4

For Pediatric Patients

• Exclusive enteral nutrition should be preferred in children with poor growth or catabolic state 4
• Immunomodulators (azathioprine, 6-mercaptopurine) are recommended for maintenance therapy 4
• Anti-TNF therapy is indicated for high-risk patients or those failing immunomodulators 4

Emerging JAK Inhibitors for Crohn's Disease

While tofacitinib has not proven effective, other JAK inhibitors show more promise:

• Filgotinib, a selective JAK1 inhibitor, demonstrated efficacy in Crohn's disease in the phase II FITZROY study 2
• Upadacitinib showed promising results in a phase II trial for moderate to severe Crohn's disease 2
• Phase III programs for both filgotinib and upadacitinib in Crohn's disease are ongoing 2

Case-Specific Considerations

There is limited evidence supporting tofacitinib use in specific Crohn's disease manifestations:

• A case report described successful treatment of esophageal Crohn's disease with tofacitinib in a patient who was refractory to TNF-α inhibitor therapy 5
• In a 48-week extension study, patients in remission at baseline receiving tofacitinib 5 mg twice daily maintained remission in 87.9% of cases (as observed) or 46.8% using non-responder imputation 6
• However, these limited findings do not override the negative results from larger controlled trials

Conclusion

Based on the available evidence, particularly the phase IIb clinical trials showing lack of efficacy, tofacitinib (Xeljanz) cannot be recommended for the treatment of Crohn's disease. Patients should instead be treated with established therapies including immunomodulators (azathioprine, mercaptopurine, methotrexate) and biologics (particularly infliximab) as recommended in current guidelines.