Predictors of treatment failure of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis with focus on haptoglobin, haptoglobin polymorphism and zonulin

Rheumatol Int. 2024 Mar;44(3):483-495. doi: 10.1007/s00296-023-05484-2. Epub 2023 Oct 17.

Abstract

According to the Assessment of SpondyloArthritis International Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axial spondyloarthritis (axSpA), patients should undergo at least two courses of non-steroidal anti-inflammatory drugs (NSAIDs) therapy. In our study, we enrolled axSpA patients both at onset and in a flare who had already been treated with NSAIDs ineffectively. Subsequently, according to the recommendations, they received modified NSAID treatment as another attempt to the first-line drug therapy and were monitored from there. We aimed to identify risk factors for treatment failure after 4 weeks (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) especially amongst zonulin and haptoglobin concentrations, and haptoglobin polymorphism. Treatment failure was observed in 71% of patients, and the following variables were contributed for occurrence of this state: higher zonulin levels, ankylosing spondylitis, X-ray sacroiliitis, magnetic resonance imaging sacroiliitis, long duration of symptoms, high BASDAI, and high value of spinal pain intensity on visual analogue scale. In addition, the following positive correlations were found: haptoglobin concentration with C-reactive protein (r = 0.56; p = 0.0004), and erythrocyte sedimentation rate (r = 0.62; p < 0.0001), as well as between zonulin levels and white blood count (r = 0.5; p = 0.0003). The results of the study presented the identified factors related to the standard treatment failure in axSpA, amongst them zonulin levels. They might be applied to point out the patients for whom the search for a more appropriate method of treatment should be considered.

Keywords: Ankylosing spondylitis; Anti-inflammatory agents; Haptoglobins; Non-steroidal; Sacroiliitis; Zonulin.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Haptoglobins / genetics
  • Haptoglobins / therapeutic use
  • Humans
  • Protein Precursors*
  • Sacroiliitis* / diagnosis
  • Spondylarthritis* / diagnosis
  • Spondylitis, Ankylosing* / diagnosis
  • Spondylitis, Ankylosing* / drug therapy
  • Spondylitis, Ankylosing* / genetics
  • Treatment Failure

Substances

  • zonulin
  • Haptoglobins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Protein Precursors