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In patients with axial spondyloarthritis, inflammation on MRI of the spine is longitudinally related to disease activity only in men: 2 years of the axial spondyloarthritis DESIR cohort
  1. Victoria Navarro-Compán1,2,
  2. Sofia Ramiro1,
  3. Robert Landewé3,4,
  4. Maxime Dougados5,
  5. Corinne Miceli-Richard5,
  6. Pascal Richette6,7,8,
  7. Désirée van der Heijde1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, University Hospital La Paz, IdiPaz, Madrid, Spain
  3. 3Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Clinical Immunology Center, University of Amsterdam, Amsterdam, The Netherlands
  4. 4Department of Rheumatology, Atrium Medical Center, Heerlen, The Netherlands
  5. 5Department of Rheumatology, Paris Descartes University, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, INSERM: Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
  6. 6Université Paris Diderot, UFR médicale, Paris, France
  7. 7APHP Hôpital Lariboisière, Fédération de Rhumatologie, Paris, France
  8. 8Inserm U1132, Hôpital Lariboisière, Paris, France
  1. Correspondence to Dr Victoria Navarro-Compán, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, Leiden 2333 RC, The Netherlands; mvictoria.navarroc{at}gmail.com

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The effects of inflammatory disease activity (DA) on radiographic progression in patients with axial spondyloarthritis (axSpA) are worse in men and smokers, but an explanation for this is lacking.1 Recently, we have found a relationship between inflammatory lesions in the sacroiliac joints (SIJs) detected by MRI and clinical DA measures in male patients, which was absent in female patients.2 Here, we investigate whether this gender-specific association between MRI-lesions and clinical DA extends to the spine.

The objectives of this study were: (i) to explore the relationship between inflammatory lesions of the spine on MRI and DA in patients with axSpA; (ii) to investigate if such a relationship is gender specific and (iii) to explore the influence of other patient-related factors on the relationship between MRI of the spine and DA.

Two-year follow-up data from 164 patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) axSpA criteria in the DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR) cohort with at least two spine MRIs available during this period were analysed.3 ,4

The relationship between MRI-spine and DA (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient’s global DA, night pain, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) was analysed by generalised estimating equations (GEEs) on absolute MRI-spine scores (Berlin method).5 Interactions between DA and a set of characteristics, including age, gender, human leucocyte antigen B27 (HLA-B27), symptom duration, smoking status and current treatment with tumour necrosis factor inhibitors (TNFis), were examined one by one. In case of a relevant interaction, a stratified analysis was performed. If a relevant interaction was absent, relevant confounding was examined for the relationship between DA and MRI of the spine by comparing the crude model (non-adjusted model) with an adjusted model (adjusted for that specific factor).

Baseline characteristics of the patients included in the study are presented in table 1.

Table 1

Characteristics of the patients with axial spondyloarthritis included in this study

Fifty per cent of patients were men, mean (SD) age was 33 (9) years, 39% were smokers, 82% carried HLA-B27 and mean symptom duration was 18 (11) months. Overall, baseline characteristics of included patients were similar to those of patients in the entire DESIR cohort.

Gender and DA had a relevant interaction on explaining variation in spinal MRI-scores (p=0.03 for ASDAS*gender); therefore, subsequent analyses were performed for men and women separately. In the fully adjusted GEE models, ASDAS, pain at night and CRP were statistically significantly related to inflammatory lesions on MRI in men, but not in women (figure 1). Beta values and 95% CIs for these DA in men were (β=0.392; 0.004 to 0.781), (β=0.185; 0.065 to 0.306) and (β=0.046; 0.012 to 0.080), respectively. In men, patient global assessment for DA (β=0.080; −0.040 to 0.200) and ESR (β=0.054; −0.015 to 0.122) showed a similar trend, but BASDAI did not have a relationship with MRI-spine, neither in male patients (β=−0.042; −0.159 to 0.074) nor in female patients. In addition, TNFi usage in men and smoking in women were associated with DA and with MRI-spine, and as such acted as confounders.

Figure 1

Longitudinal relationship between clinical disease activity (DA) measures and inflammation degree (Berlin score) on MRI of the spine stratified for gender. Each graph represents a separate model for the relationship between the specific clinical DA measure and spinal MRI-inflammation with a generalised estimating equation (GEE) model making use of data from baseline, 1year and 2 years of follow-up. All models were adjusted for current treatment with tumour necrosis factor alpha inhibitors and smoking status. Markers (diamond for men and square for women) represent the regression coefficient and the surrounding lines represent the 95% CIs. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; pt’s global disease, patient's global assessment for disease activity.

In conclusion, in patients with axSpA, DA and inflammatory lesions on spinal MRI are associated, but only in male patients, and not in female patients. This relationship was confounded by smoking (women) and TNFi usage (men) but remained intact after statistical adjustment. This finding confirms previous findings with MRI of the SIJ2 and shows a different expression of axSpA between genders: that is, while in men clinical signs and symptoms coincide with MRI-positivity and with subsequent structural damage, in women symptoms attributed to axSpA (and measured by patient-reported outcomes) occur independently of MRI-inflammation and subsequent structural damage. The reasons for such gender-related uncoupling are unknown and deserve further research. Finally, within the possible limitations for this study, the lack of inflammation assessment at the posterolateral elements or axial enthesis and the presence of a floor effect need to be considered.

Acknowledgments

This study is conducted under the umbrella of the French Society of Rheumatology and Institut National de la Santé et de la Recherche Médicale (INSERM). The database management is performed within the Department of Epidemiology and Biostatistics (Professor Paul Landais, D.I.M., Nîmes, France). An unrestricted grant from Pfizer was allocated for the 10 years of follow-up of the recruited patients. The authors thank the different regional participating centres: Professor Maxime Dougados (Paris—Cochin B), Professor André Kahan (Paris—Cochin A), Professor Olivier Meyer (Paris—Bichat), Professor Pierre Bourgeois (Paris—La Pitié Salpetrière), Professor Francis Berenbaum (Paris—Saint Antoine), Professor Pascal Claudepierre (Créteil), Professor Maxime Breban (Boulogne Billancourt), Dr Bernadette Saint-Marcoux (Aulnay-sous-Bois), Professor Philippe Goupille (Tours), Professor Jean-Francis Maillefert (Dijon), Dr Xavier Puéchal, Dr Emmanuel Dernis (Le Mans), Professor Daniel Wendling (Besançon), Professor Bernard Combe (Montpellier), Professor Liana Euller-Ziegler (Nice), Professor Philippe Orcel, Dr Pascal Richette (Paris—Lariboisière), Professor Pierre Lafforgue (Marseille), Dr Patrick Boumier (Amiens), Professor Jean-Michel Ristori, Professor Martin Soubrier (Clermont-Ferrand), Dr Nadia Mehsen (Bordeaux), Professor Damien Loeuille (Nancy), Professor René-Marc Flipo (Lille), Professor Alain Saraux (Brest), Professor Corinne Miceli (Le Kremlin Bicêtre), Professor Alain Cantagrel (Toulouse) and Professor Olivier Vittecoq (Rouen). The authors also thank URC-CIC Paris Centre (Jean Marc Tréluyer) for the implementation and monitoring of the study.

References

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Footnotes

  • Contributors VN-C, SR, RL and DvdH designed the study. VN-C and SR performed the statistical analyses. RL, MD and DvdH critically interpreted the results. VN-C wrote the first draft of the manuscript. All authors reviewed the draft version and approved the final manuscript.

  • Funding This project was supported by an unrestricted grant from Pfizer.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study is conducted under the umbrella of the French Society of Rheumatology and Institut National de la Santé et de la Recherche Médicale (INSERM).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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