Can Tofacitinib (tofacitinib) be used to treat ankylosing spondylitis?

Tofacitinib for Ankylosing Spondylitis: Treatment Recommendations

Tofacitinib can be used for ankylosing spondylitis (AS), but it is not recommended as a first-line or second-line therapy due to its limited evidence base compared to TNF inhibitors and IL-17 inhibitors. 1

Treatment Algorithm for Ankylosing Spondylitis

First-line Therapy

• NSAIDs are strongly recommended as first-line therapy for active AS 1
• Continuous treatment with NSAIDs is conditionally recommended over on-demand treatment 1

Second-line Therapy (after NSAID failure)

• TNF inhibitors (TNFi) are strongly recommended as the preferred second-line therapy 1
• IL-17 inhibitors (secukinumab or ixekizumab) are strongly recommended as alternatives but conditionally recommended to be used after TNFi 1

Third-line Therapy Options

• For patients who fail TNFi:
  • If primary non-response to TNFi: Switch to IL-17 inhibitors (secukinumab or ixekizumab) 1
  • If secondary non-response to TNFi: Switch to a different TNFi 1

Where Tofacitinib Fits in Treatment

• Tofacitinib is conditionally recommended only in specific situations:
  • When TNFi and IL-17 inhibitors are not available or contraindicated 1
  • In patients with prominent peripheral arthritis when TNFi are not available 1
  • In patients with coexisting ulcerative colitis where TNFi is not an option (tofacitinib is preferred over IL-17 inhibitors) 1

Efficacy of Tofacitinib in Ankylosing Spondylitis

• Phase III randomized controlled trial demonstrated that tofacitinib 5 mg twice daily was significantly more effective than placebo:
  • ASAS20 response: 56.4% vs 29.4% (p<0.0001) 2
  • ASAS40 response: 40.6% vs 12.5% (p<0.0001) 2
• Efficacy was observed in both biologic-naïve and TNFi-inadequate responder patients 3
• The magnitude of response was generally greater in biologic-naïve patients compared to TNFi-inadequate responders 3

Safety Considerations

• Safety profile in AS appears consistent with that observed in other indications 2
• Common adverse events include:
  • Herpes zoster infections (2.3% in tofacitinib group) 2
  • Hepatic events (2.3% in tofacitinib group) 2
  • Serious infections (0.8% in tofacitinib group) 2
• Pharmacokinetic characteristics in AS patients are similar to those in other inflammatory conditions, with a half-life of about 3 hours 4
• Tofacitinib is primarily metabolized by CYP3A4 with approximately 70% hepatic metabolism and 30% renal excretion 4

Special Considerations

• Contraindications to TNFi: If contraindication is congestive heart failure or demyelinating disease, IL-17 inhibitors are preferred over tofacitinib 1
• Infectious contraindications: If contraindication to TNFi is tuberculosis or other chronic infections, sulfasalazine is preferred over tofacitinib or IL-17 inhibitors 1
• Body mass index (BMI): Efficacy of tofacitinib is generally maintained across different BMI categories, although patients with BMI ≥30 kg/m² may show less response for some endpoints 5
• Coexisting ulcerative colitis: Tofacitinib is approved for ulcerative colitis and should be considered over IL-17 inhibitors in AS patients with this comorbidity 1

Key Pitfalls to Avoid

• Do not use tofacitinib as first-line therapy before trying NSAIDs 1
• Do not use tofacitinib before TNFi or IL-17 inhibitors unless specifically indicated 1
• Do not switch to a biosimilar of the first TNFi in patients who fail TNFi therapy (strongly recommended against) 1
• Monitor for infections, particularly herpes zoster, as these are known risks with JAK inhibitors 2

In conclusion, while tofacitinib has demonstrated efficacy in AS and is FDA-approved for this indication, current guidelines from the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network conditionally recommend TNFi and IL-17 inhibitors over tofacitinib due to their more extensive evidence base and established safety profiles 1.