Background

Spondyloarthritis (SpA) and psoriatic arthritis (PsA) treatment guidelines recommend anti-TNF agents as first-line biologics, with anti-IL17 agents (secukinumab, ixekizumab) as alternatives. Most prescribing data comes from European and North American registries where anti-TNF dominates 70-80% of biologic use.

Real-World Data: IMSS Mérida, Yucatán

We analyzed a cohort of SpA/PsA patients from Hospital General Regional No.1, IMSS, Mérida, Yucatán — a population with 65-75% Native American (Maya) ancestry.

Demographics (n=89):

• PsA: 53 (59.6%), AxSpA/EA: 29 (32.6%), CUCI+EA: 3 (3.4%), Uveitis+EA: 2 (2.2%)
• Female: 65.2% (notably higher than typical SpA registries where males predominate)
• Mean age: 53 years (range 23-84)
• High proportion of Maya surnames (Dzul, Canul, Kantun, Uicab, Tuyub, etc.)

Biologic use (patients ever exposed):

• Anti-TNF total: 27 patients
  • Etanercept: 9, Golimumab: 7, Adalimumab: 6, Certolizumab: 5
• Anti-IL17 total: 17 patients
  • Secukinumab: 12, Ixekizumab: 5
• JAK inhibitors: 2 (Upadacitinib 1, Baricitinib 1)
• Treatment switches/failures documented: 5

Key ratios:

• Anti-TNF:Anti-IL17 = 1.6:1 (vs typical registries 4-5:1)
• Anti-IL17 represents 37% of biologic exposure (vs ~15-20% in European registries)
• Secukinumab is the MOST prescribed single biologic agent (12 patients)

The Hypothesis

The unusually high adoption of anti-IL17 agents in this Maya-mestizo cohort may reflect:

1. Clinician-observed superior efficacy in this population, driving empirical preference
2. IL-17 pathway genetic variants that differ in Indigenous Mexican populations — ALL 24 IL-17/IL-23 pathway genes have ZERO published frequency data in Mexican populations (FinnGen pathway analysis identified IL12B p=2.1×10⁻⁴³, TRAF3IP2 p=5.2×10⁻²², IL23R p=1.0×10⁻¹¹ as top signals in European SpA/PsA)
3. IMSS formulary dynamics — secukinumab availability may have increased relative to certain anti-TNF agents (certolizumab desabasto documented in records)
4. Population-specific disease phenotype — female predominance (65% vs expected 30-40% in AxSpA) suggests a different disease presentation in Maya-mestizo populations

Pharmacogenomic Implications

The IL-17/IL-23 pathway genes requiring urgent study in this population:

• IL23R (rs11209026): Anti-IL23 response predictor — NO Mexican data
• IL12B (rs918518): Strongest genomic signal in psoriasis — NO Mexican data
• IL17A (rs80167352): IL-17 production — NO Mexican data
• TRAF3IP2 (rs33980500): Downstream IL-17 signaling — NO Mexican data
• TYK2 (rs34536443): Known to be absent/rare in Indigenous Mexicans (PMID 31434951)

Female Predominance Paradox

AxSpA classically has a male:female ratio of 2-3:1. In this cohort, females represent 65.2%. Possible explanations:

• Ascertainment bias (rheumatology clinic vs population-based)
• PsA predominance (53/89) which has more equal sex ratio
• OR: True population difference in Maya-mestizo SpA phenotype — HLA-B27 frequencies in Indigenous Mexican populations are poorly characterized

Critical Knowledge Gap

This cohort reveals that treatment patterns in Mexican public healthcare diverge significantly from international guidelines. Without pharmacogenomic data on IL-17 pathway genes in Indigenous populations, we cannot determine if the empirical anti-IL17 preference is pharmacogenomically justified or merely formulary-driven.

Population: 89 SpA/PsA patients, IMSS HGR1 Mérida, Yucatán, México (65-75% Native American ancestry) Analysis: STORM pharmacogenomic model (rheumascore.xyz/storm.html) References: PMID 31434951 (TYK2 in Mexicans), PMID 26812836 (RIBEF pharmacogenomics), PMID 24926019 (Genetics of Mexico)