A patient with ankylosing spondylitis who developed paradoxical psoriasis while on a tumor necrosis factor‑alpha inhibitor—what is the recommended next step in management?

Management of Paradoxical Psoriasis During TNF Inhibitor Therapy for Ankylosing Spondylitis

Switch to an IL-17 inhibitor (secukinumab or ixekizumab) rather than continuing or switching to another TNF inhibitor, as the presence of psoriasis makes IL-17 inhibitors the preferred biologic class for treating the underlying ankylosing spondylitis. 1

Why IL-17 Inhibitors Are the Optimal Choice

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, and paradoxical psoriasis represents a form of treatment failure that warrants switching mechanism of action 1. The development of paradoxical psoriasis during TNF inhibitor therapy indicates an aberrant immune response where TNF blockade triggers compensatory upregulation of type 1 interferons and IL-23/IL-17 pathways 2.

• IL-17 inhibitors effectively treat both the ankylosing spondylitis and the paradoxical psoriasis simultaneously, eliminating the need to manage two separate conditions with different therapies 1
• Secukinumab is FDA-approved for ankylosing spondylitis at 150 mg subcutaneously with loading doses at weeks 0,1,2,3, and 4, then every 4 weeks, with the option to increase to 300 mg if disease remains active 3
• The presence of coexistent psoriasis specifically favors IL-17 inhibitors over TNF inhibitors according to current treatment algorithms 1

Why Not Continue or Switch TNF Inhibitors

Continuing the current TNF inhibitor is contraindicated because paradoxical psoriasis represents a class effect seen with all TNF inhibitors (infliximab, adalimumab, etanercept), with infliximab and etanercept having the highest incidence 4, 5. While 80% of patients in one case series achieved remission by continuing therapy through the flare 4, this approach carries significant risk:

• Switching to a different TNF inhibitor does not reliably prevent recurrence of paradoxical psoriasis, as this is a class-wide phenomenon affecting the TNF-α pathway 5
• The mechanism involves dysregulated interferon production and IL-23/Th17 axis activation that persists across all TNF inhibitors 2
• Guidelines do not support TNF inhibitor continuation when significant adverse effects like paradoxical psoriasis develop 1

Why Not Use JAK Inhibitors

JAK inhibitors (tofacitinib, upadacitinib) are conditionally recommended only when both TNF inhibitors AND IL-17 inhibitors are contraindicated or unavailable 1. While recent case reports show JAK inhibitors successfully treating TNF-induced psoriasis 2, they remain third-line for ankylosing spondylitis:

• TNF inhibitors and IL-17 inhibitors are strongly favored over JAK inhibitors due to longer safety data and more robust evidence in axial spondyloarthritis 1
• JAK inhibitors have concerning safety signals including increased risk of major adverse cardiovascular events and malignancy in certain populations 1
• Reserve JAK inhibitors for patients who fail both TNF and IL-17 inhibitor classes 1

Treatment Algorithm

1. Immediately discontinue the current TNF inhibitor upon diagnosis of paradoxical psoriasis 1

2. Initiate secukinumab 150 mg subcutaneously at weeks 0,1,2,3, and 4, then every 4 weeks 3

   • If ankylosing spondylitis remains active after 3-6 months, increase to 300 mg every 4 weeks 3
   • Alternative: ixekizumab with comparable efficacy 1

3. Assess response at 12-16 weeks using validated measures (BASDAI, ASDAS) for ankylosing spondylitis and clinical assessment for psoriasis 1

4. If inadequate response to IL-17 inhibitor, consider switching to a different IL-17 inhibitor or escalating to JAK inhibitor therapy 1

Critical Pitfalls to Avoid

Do not add topical or systemic psoriasis therapy while continuing the TNF inhibitor, as this addresses the symptom rather than the underlying cause and exposes the patient to unnecessary polypharmacy 1. The paradoxical psoriasis will not reliably resolve until the offending TNF inhibitor is discontinued 5.

Do not use conventional DMARDs (methotrexate, sulfasalazine, leflunomide) for axial disease, as these agents show no efficacy for spinal manifestations of ankylosing spondylitis 1. Sulfasalazine is only appropriate if persistent peripheral arthritis exists and biologics are contraindicated 1.

Do not delay switching therapy hoping the paradoxical psoriasis will spontaneously resolve, as the median time to development is 5-12 months after TNF inhibitor initiation, and continuation risks worsening cutaneous disease 5.