What is the recommended next‑step management for an ankylosing spondylitis patient who has not achieved an adequate response after a full 12–16‑week trial of secukinumab (150 mg or 300 mg subcutaneously every 4 weeks)?

Management of Ankylosing Spondylitis Unresponsive to Secukinumab

Switch to a TNF inhibitor (adalimumab, etanercept, infliximab, golimumab, or certolizumab pegol) as the next-step therapy for an AS patient who has failed secukinumab after 12–16 weeks. 1

Understanding the Clinical Context

The 2019 American College of Rheumatology/Spondylitis Association of America guidelines explicitly address this scenario and distinguish between primary non-response (never achieved meaningful improvement) versus secondary non-response (initial response followed by loss of efficacy). 1

Key Decision Point: Type of Non-Response

For primary non-response to secukinumab (no clinically meaningful improvement over 12–16 weeks):

• Switch to a TNF inhibitor rather than trying another IL-17 inhibitor (ixekizumab), as the lack of response suggests IL-17 blockade is not the appropriate therapeutic target for this patient 1
• The ACR panel reasoning: if secukinumab failed from the outset, TNF—not IL-17—is likely the key inflammatory mediator driving disease activity 1

For secondary non-response to secukinumab (initial response followed by relapse):

• Still switch to a TNF inhibitor as the preferred next option 1
• While ixekizumab could theoretically be considered, no head-to-head trials compare switching within the IL-17 class versus switching to TNF inhibitors in this scenario 1

What NOT to Do: Critical Pitfalls

Do not add methotrexate or sulfasalazine to secukinumab in an attempt to salvage the response—the ACR conditionally recommends against this strategy in favor of switching to a new biologic entirely 1

Do not switch to a biosimilar of secukinumab (if one existed)—the ACR strongly recommends against this as clinical response would not be expected to differ 1

Do not add conventional synthetic DMARDs (methotrexate, sulfasalazine, leflunomide) for axial disease, as these agents have no proven efficacy for axial manifestations of AS 2

Confirming Adequate Trial of Secukinumab

Before switching, verify the patient received an adequate trial:

• Correct dosing: 150 mg subcutaneously at weeks 0,1,2,3, and 4, then every 4 weeks 3
• Adequate duration: Full 12–16 weeks, as improvements may continue to accrue through week 16 4, 5
• Consider dose escalation only if: Patient is on 150 mg and has shown partial response; escalation to 300 mg every 4 weeks is FDA-approved for AS patients with continued active disease 3

Important Caveat on Dose Escalation

Recent evidence from the ASLeap trial (2025) showed that dose escalation from 150 mg to 300 mg in patients who failed to achieve inactive disease at week 16 provided minimal additional benefit—only 8.8% achieved ASDAS <1.3 at week 52 with dose escalation versus 6.7% who remained on 150 mg 6. This suggests that if a patient has not responded adequately by 16 weeks on 150 mg, switching drug class is more appropriate than dose escalation.

Recommended TNF Inhibitor Options

All five FDA-approved TNF inhibitors for AS are reasonable choices: 1, 2

• Adalimumab
• Etanercept
• Infliximab
• Golimumab
• Certolizumab pegol

Selection should be based on:

• Patient preference for administration route (subcutaneous vs. intravenous)
• Dosing frequency
• Comorbidities (e.g., congestive heart failure is a contraindication to TNF inhibitors)
• Insurance coverage

Expected Response Rates

Observational data suggest that 25–40% of AS patients who switch from one biologic class to another will achieve a meaningful response (≥50% improvement in Bath AS Disease Activity Index) 1

Monitoring After Switch

Reassess clinical response at 12–16 weeks after initiating the TNF inhibitor using standardized measures: 7

• ASAS20/40 response criteria
• ASDAS (Ankylosing Spondylitis Disease Activity Score)
• Patient global assessment
• Bath AS Disease Activity Index

Special Considerations

If the patient has contraindications to TNF inhibitors (active tuberculosis, chronic infection, high risk of recurrent infections):

• Address the contraindication first (e.g., treat latent TB before starting TNF inhibitor) 1
• If contraindications cannot be mitigated, sulfasalazine may be considered only if there is active peripheral arthritis (not for axial symptoms) 1
• JAK inhibitors (tofacitinib, upadacitinib) should be reserved for situations where both TNF inhibitors and IL-17 inhibitors are contraindicated or unavailable 2

If the patient has coexistent inflammatory bowel disease:

• Exercise particular caution, as secukinumab may worsen IBD 3
• TNF inhibitors (especially infliximab and adalimumab) are preferred as they treat both AS and IBD 3