Treatment Recommendation for Ankylosing Spondylitis After Multiple Treatment Failures
Switch to an IL-17 inhibitor (secukinumab or ixekizumab) immediately, as this is the guideline-recommended next step for patients with primary non-response to a TNF inhibitor, particularly when a JAK inhibitor has also failed. 1, 2
Rationale for IL-17 Inhibitor Selection
Your patient meets the definition of primary non-response to Enbrel (etanercept), defined as absence of clinically meaningful improvement over 3-6 months after treatment initiation. 1 The 2019 ACR/SAA/SPARTAN guidelines explicitly recommend secukinumab or ixekizumab over a second TNF inhibitor in patients with primary non-response to the first TNF inhibitor. 1, 2
Key guideline hierarchy for this scenario:
- IL-17 inhibitors (secukinumab/ixekizumab) are conditionally recommended over a different TNF inhibitor after primary TNF non-response 1
- IL-17 inhibitors are conditionally recommended over tofacitinib (and by extension, other JAK inhibitors like Rinvoq/upadacitinib) 1
- Guidelines strongly recommend against switching to a biosimilar of the first TNF inhibitor 1
Why Not Continue or Switch JAK Inhibitors
The guidelines rank TNF inhibitors, secukinumab, and ixekizumab as favored over JAK inhibitors (tofacitinib) for AS treatment. 2 Since Rinvoq (upadacitinib) provided no relief, continuing this class is not optimal. 2 The evidence base for IL-17 inhibitors in AS is substantially stronger than for JAK inhibitors. 1
Choosing Between Secukinumab and Ixekizumab
Both secukinumab and ixekizumab demonstrate similar efficacy in AS with comparable clinical response rates. 2 Critical decision point: If your patient has any history of inflammatory bowel disease (IBD), you should reconsider and use a TNF inhibitor monoclonal antibody instead, as IL-17 inhibitors can worsen IBD. 2
Practical dosing:
- Secukinumab: 150 mg subcutaneous injection at weeks 0,1,2,3,4, then monthly (may increase to 300 mg if needed)
- Ixekizumab: 160 mg subcutaneous injection at week 0, then 80 mg every 4 weeks
Alternative: TNF Inhibitor Monoclonal Antibody
If IL-17 inhibitors are contraindicated or unavailable, switch to a TNF inhibitor monoclonal antibody (adalimumab, infliximab, golimumab, certolizumab) rather than another TNF receptor fusion protein like etanercept. 2 This represents a different mechanism within the TNF inhibitor class and may provide benefit despite etanercept failure. 1
Critical Management Pitfalls to Avoid
Do not add methotrexate or sulfasalazine to the new biologic therapy for axial disease—guidelines explicitly recommend against co-treatment with conventional synthetic DMARDs for axial manifestations. 1, 2 Sulfasalazine is only recommended for persistent peripheral arthritis when TNF inhibitors are contraindicated. 1
Do not discontinue or taper biologics once disease control is achieved, as 60-74% of patients relapse upon discontinuation. 2 The guidelines conditionally recommend against discontinuation or dose tapering as a standard approach. 1
Do not use systemic glucocorticoids for axial disease—guidelines strongly recommend against this. 1 Local glucocorticoid injections may be considered for isolated sacroiliitis, enthesitis, or peripheral arthritis if present. 1
Monitoring and Response Assessment
Assess response to the IL-17 inhibitor at 3-6 months using clinical measures of disease activity (BASDAI, ASDAS, patient global assessment). 2 If there is inadequate response at 3-6 months, this constitutes primary non-response to the IL-17 inhibitor, and you should then switch to a different TNF inhibitor monoclonal antibody. 1
Continue Celebrex (celecoxib) during the transition to IL-17 inhibitor therapy, as NSAIDs remain foundational treatment and can be used concomitantly with biologics. 3 Celecoxib 200 mg daily or 100 mg twice daily has demonstrated efficacy in AS for pain, global disease activity, and functional impairment. 3
Physical Therapy Integration
Strongly recommend physical therapy as an essential component of treatment—guidelines give this a strong recommendation with moderate quality evidence. 1 Active physical therapy interventions (supervised exercise) are preferred over passive interventions (massage, ultrasound, heat). 1