Can upadacitinib (Janus kinase inhibitor) be used in patients with axial spondyloarthritis (axial SpA) who have had an inadequate response or intolerance to conventional therapies?

Can Upadacitinib Be Used in Axial SpA Patients?

Yes, upadacitinib is indicated and effective for the treatment of active axial spondyloarthritis (axSpA), including both ankylosing spondylitis and non-radiographic axial SpA, particularly after inadequate response to NSAIDs or biologic DMARDs. 1

Evidence Supporting Use in Axial SpA

Regulatory Approval and Guideline Support

• Upadacitinib has been proven effective and is indicated for ankylosing spondylitis (AS) treatment, distinguishing it from other JAK inhibitors like filgotinib which lacks this indication 1

• The 2022 GRAPPA guidelines extrapolate evidence from ankylosing spondylitis trials to recommend JAK inhibitors (including upadacitinib, tofacitinib, and filgotinib) for axial psoriatic arthritis based on phase II and phase II-III RCT data 1

Clinical Trial Efficacy Data

For biologic-naive patients with ankylosing spondylitis:

• In the SELECT-AXIS 1 trial, 52% of patients achieved ASAS40 response at week 14 with upadacitinib 15 mg versus 26% with placebo (p=0.0003; treatment difference 26%) 2
• Efficacy was sustained through 1 year, with ≥70% achieving ASAS40 and ≥81% based on as-observed analyses at week 64 3

For non-radiographic axial SpA:

• In SELECT-AXIS 2,45% achieved ASAS40 at week 14 with upadacitinib versus 23% with placebo (p<0.0001; treatment difference 22%) 4

For biologic-experienced patients:

• At week 52 in bDMARD-inadequate responders, 66% achieved ASAS40, 57% achieved ASDAS low disease activity, and 26% achieved ASDAS inactive disease 5
• Efficacy was similar regardless of prior TNF inhibitor versus IL-17 inhibitor exposure 5

Treatment Algorithm for Axial SpA

First-Line After NSAID Failure (Biologic-Naive)

TNF inhibitors remain first-line for most patients, but upadacitinib 15 mg once daily is an appropriate alternative, particularly when:

• TNF inhibitors are contraindicated 1
• Patient preference favors oral therapy over injectable biologics 2, 3
• Concomitant inflammatory bowel disease is present (see special considerations below) 1

After Anti-TNF Failure

Primary non-response (lack of initial efficacy):

• Swapping to JAK inhibitors including upadacitinib is recommended with 91% expert agreement 1
• This represents a change in mechanism of action, which is preferred over switching within the TNF inhibitor class 1

Secondary non-response (loss of response) or intolerance:

• Multiple options exist: dose escalation of current TNF inhibitor, switching to another TNF inhibitor, or swapping to JAK inhibitors 1
• JAK inhibitors can be considered with 95-100% expert agreement depending on clinical context 1

Special Considerations for IBD-Associated Axial SpA

Active Axial SpA with Active IBD

• TNF inhibitors (infliximab, adalimumab) remain first-line 1
• After anti-TNF failure, JAK inhibitors can be considered with 95% agreement 1
• Upadacitinib has dual indication: approved by EMA for both Crohn's disease and ankylosing spondylitis, making it particularly suitable for this population 1

Active Axial SpA with IBD in Remission

• After primary anti-TNF non-response, swapping to JAK inhibitors is recommended with 91% agreement 1
• After secondary anti-TNF failure, JAK inhibitors can be considered with 100% agreement 1
• Treatment should focus on the rheumatological disease when IBD is quiescent 1

Safety Profile Through 1 Year

Adverse event rates are comparable to placebo in short-term studies:

• Week 14 adverse events: 48% with upadacitinib versus 46% with placebo 4
• Serious adverse events: 3% with upadacitinib versus 1% with placebo 4

Long-term safety through 1 year (237.6 patient-years exposure):

• No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths reported 3
• Most common adverse event: increased creatine phosphokinase (9% versus 2% placebo) 2
• Herpes zoster occurred in 1% of patients 4
• Neutropenia occurred in 3% of patients 4

Critical Caveats

Contraindications to consider:

• Active serious infections require treatment before initiating upadacitinib 6
• Screen for latent tuberculosis, hepatitis B and C before initiation 6, 7
• Baseline monitoring should include complete blood count with differential, liver enzymes, and lipid panel 6

Medications that should NOT be used:

• Sulfasalazine and methotrexate are not recommended for purely axial disease due to lack of efficacy 1
• IL-17 inhibitors are absolutely contraindicated in active IBD as they can exacerbate Crohn's disease 7
• Etanercept is ineffective in Crohn's disease and can trigger new-onset disease 1

Monitoring requirements:

• Ongoing monitoring for signs of infection, particularly herpes zoster 6
• Monitor for venous thromboembolism signs 6
• Serial complete blood counts to assess for cytopenias 6
• Do not automatically discontinue unless serious infection or malignancy is confirmed 6