What is the next best step for a patient with ankylosing spondylitis who has a history of back pain, a family history of AS, and has experienced a mild skin reaction to Enbrel (etanercept) with no relief after 1 month of Rinvoq (upadacitinib) use?

Next Best Step: Switch to IL-17 Inhibitor (Secukinumab or Ixekizumab)

For this patient with active ankylosing spondylitis who has failed both a TNF inhibitor (Enbrel/etanercept) and a JAK inhibitor (Rinvoq/upadacitinib), the next best step is to switch to an IL-17 inhibitor—specifically secukinumab or ixekizumab—rather than trying a second TNF inhibitor. 1

Rationale for IL-17 Inhibitor Over Second TNF Inhibitor

• The 2019 ACR/SAA/SPARTAN guidelines specifically recommend secukinumab or ixekizumab over a second TNF inhibitor in patients with primary non-response to the first TNF inhibitor. 1

• Primary non-response is defined as absence of clinically meaningful improvement over 3-6 months after treatment initiation, which applies to this patient who had no relief after 1 month on Enbrel (though the mild skin reaction also contributed to discontinuation). 1

• The guidelines explicitly recommend against switching to a biosimilar of the first TNF inhibitor in this scenario. 1

Why Not Continue or Try Another JAK Inhibitor

• Rinvoq (upadacitinib) is a JAK inhibitor, and the guidelines rank TNF inhibitors, secukinumab, and ixekizumab as favored over tofacitinib (another JAK inhibitor) for AS treatment. 1

• One month may be insufficient to assess full response to Rinvoq, but given the patient has active disease with no relief, continuing is not optimal. The guidelines define primary non-response as occurring over 3-6 months, but clinical judgment in the context of persistent active symptoms supports switching. 1

Specific Medication Selection: Secukinumab vs Ixekizumab

Both IL-17 inhibitors are appropriate options, but consider the following:

• Both secukinumab and ixekizumab have demonstrated efficacy in AS with similar clinical response rates. 1

• If the patient has comorbid inflammatory bowel disease (IBD), this creates a critical caveat: IL-17 inhibitors can potentially worsen or trigger IBD, so a TNF inhibitor monoclonal antibody (adalimumab, infliximab, certolizumab, or golimumab) would be preferred despite the prior Enbrel failure. 2

• If the patient has recurrent uveitis, TNF inhibitor monoclonal antibodies are preferred over etanercept, but IL-17 inhibitors are also reasonable options. 2

• The mild skin reaction to Enbrel does not contraindicate IL-17 inhibitors, as they have different mechanisms and side effect profiles. 3

Alternative Consideration: TNF Inhibitor Monoclonal Antibody

If there are contraindications to IL-17 inhibitors or patient/insurance factors favor trying another TNF inhibitor class:

• Switch to a TNF inhibitor monoclonal antibody (adalimumab, infliximab, certolizumab, or golimumab) rather than another TNF receptor fusion protein like etanercept. 2, 4

• Etanercept (Enbrel) is a TNF receptor fusion protein, while the monoclonal antibodies have different pharmacokinetics and may work when etanercept fails. 2, 4, 5

• This is particularly important if the patient has comorbid IBD or recurrent uveitis, where monoclonal antibodies are superior to etanercept. 2

Common Pitfalls to Avoid

• Do not add methotrexate or other conventional synthetic DMARDs (sulfasalazine, leflunomide) to biologic therapy for axial disease, as guidelines recommend against co-treatment with low-dose methotrexate in AS. 1

• Do not prematurely discontinue or taper biologics once disease control is achieved, as 60-74% of patients relapse upon discontinuation. 1, 2

• Do not use etanercept if the patient has inflammatory bowel disease, as it may exacerbate IBD symptoms and is not approved for Crohn's disease or ulcerative colitis. 2, 3

• Ensure adequate trial duration before declaring treatment failure: while 1 month on Rinvoq is short, the combination of no relief plus prior TNF inhibitor failure supports switching rather than waiting the full 3-6 months. 1

Monitoring and Follow-up

• Assess response to the new IL-17 inhibitor at 3-6 months using clinical measures of disease activity (BASDAI, ASDAS, patient global assessment, spinal mobility). 1

• Regular monitoring with CBC, CMP, and CRP every 3-4 months is recommended for patients receiving biologic therapy. 2

• Screen for tuberculosis and hepatitis B before initiating any new biologic therapy. 3