University of Groningen
Clinical and spinal radiographic outcome in axial spondyloarthritis
Maas, Fiona
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Publication date: 2017
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Maas, F. (2017). Clinical and spinal radiographic outcome in axial spondyloarthritis: Results from the GLAS cohort. Rijksuniversiteit Groningen.
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Chapter 9
Male and female patients with axial
spondyloarthritis experience disease
activity, physical function, and quality of life
differently: results from the GLAS cohort
Suzanne Arends Fiona Maas Freke Wink Monique Efde Hendrika Bootsma Eveline van der Veer Elisabeth Brouwer Anneke Spoorenberg
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Sir,
Ankylosing spondylitis (AS) is an auto-inflammatory rheumatic disease that predominantly affects the axial skeleton. The disease usually starts in the second or third decade of life and onset after 45 years of age is rare. AS seems to occur more often in males than in females (ratio 2:1) [1]. There are gender differences in clinical presentation of AS. Women tend to have milder disease and may therefore be under diagnosed. Male AS patients are more likely to develop radiographic spinal damage [2].
Patient-reported assessments are widely used to evaluate disease activity and outcome. In AS, clinical decision making is mainly based on patient-reported measures. However, there are differences in how men and women approach their own health and how they communicate their health problems [3,4]. Since these gender differences may have clinical implications, our aim was to investigate whether patient-reported assessments of disease activity, physical function, and quality of life differ between male and female patients with axial spondyloarthritis (SpA).
All consecutive patients from the Groningen Leeuwarden Axial SpA (GLAS) cohort who visited the outpatient clinic between January 2011 and December 2012 were included in this cross-sectional analysis. GLAS is an ongoing prospective observational cohort study which started in 2004, including consecutive outpatients fulfilling the modified New York criteria for AS who started tumor necrosis factor-alpha (TNF-α) blocking therapy because of active disease [5]. In 2009, this inclusion was extended to all consecutive axial SpA outpatients, irrespective of treatment regimen. Patients fulfilling the ASAS axial SpA criteria including MRI were added in order to include also patients with early disease (<10% of study population). The GLAS cohort was approved by the local ethics committees of the MCL and UMCG, and all patients provided written informed consent according to the Declaration of Helsinki. Disease activity was assessed using Bath AS Disease Activity Index (BASDAI), AS Disease Activity Score (ASDAS; calculated from BASDAI questions 2, 3 and 6, patient global disease activity (GDA), and, C-reactive protein (CRP)), swollen joint index (range 0-44), and tender joint index (range 0-46). Physical function was assessed using Bath AS Functional Index (BASFI) and quality of life using AS Quality of Life (ASQoL) questionnaire.
Statistical analysis was performed with IBM SPSS Statistics 20 (SPSS, Chicago, IL, USA). Results were expressed as number of patients (%), mean ± standard deviation (SD) or median (range)
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for categorical, normally distributed and non-normally distributed data, respectively.Chi-Square test, Independent samples t test, and Mann-Whitney U test were used as appropriate to compare differences between male and female patients. Multivariable logistic regression was performed to correct the association between patient-reported assessments and gender for differences in patient characteristics. P-values <0.05 were considered as statistically significant.
Of the 466 included patients, mean age was 45 years (SD ± 13), mean duration of symptoms 17 years (range 0-61), 66% were male, and 80% HLA-B27+. Male patients were significantly older, had longer disease duration, and were more frequently HLA-B27+ compared to female patients. History of extra-articular manifestations and current medication use were comparable between both sexes (Table 1).
At group level, female patients with axial SpA scored significantly higher on patient-reported measures of disease activity (BASDAI, patient GDA, and tender joints) than male patients. The ASDAS, combining subjective and objective aspects of disease activity, was also significantly higher in females. Objective measures of disease activity (CRP and swollen joints) were comparable between sexes. Patient-reported measures of physical function (BASFI) and quality of life (ASQoL) were significantly worse in female patients (Table 1; Supplementary Figure 1). All differences remained statistically significant after correcting for age, disease duration, and HLA-B27 status in multivariable logistic regression analysis (data not shown). A recent post-hoc analysis using pooled data from 4 randomized controlled trials showed significantly less improvement in BASDAI, ASDAS, and BASFI after 12 weeks of TNF-α blocking therapy in female AS patients [6]. Our cross-sectional study in daily clinical practice included a broad population of axial SpA patients treated according to the ASAS consensus treatment
[7]. The results showed that patient-reported assessments of disease activity and outcome were all significantly worse in female axial SpA patients. The gender difference in ASDAS can also be explained by subjective aspects of disease activity, since we found similar CRP levels for males and females. We recommend being aware of these differences when interpreting BASDAI and also ASDAS results in clinical studies. In general, women are more likely to have a lower pain threshold and lower tolerance to pain than men, but data also suggest that women are more likely to be inadequately treated [3]. Further research is needed to investigate the underlying mechanism of gender differences in experiencing disease activity and outcome in axial SpA.
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In conclusion, this cross-sectional analysis in a large cohort of axial SpA patients demonstrated that patient-reported measures of disease activity, physical function, and quality of life are significantly worse in females.
Table 1. Characteristics and clinical assessments in male and female patients with axial SpA.
All patients (n=466) Males (n=309) Females (n=157) P-value*
Age (yrs) 45 ± 13 46 ± 13 43 ± 12 0.008
Symptom duration (yrs) 17 (0-61) 18 (0-61) 16 (0-54) 0.007 Time since diagnosis 8 (0-54) 10 (0-54) 6 (0-48) 0.005
HLA-B27+ 354 (80) 244 (83) 110 (74) 0.038
History of IBD 62 (14) 35 (12) 27 (18) 0.075
History of uveitis 148 (32) 100 (33) 48 (31) 0.726 History of psoriasis 52 (11) 35 (11) 17 (11) 0.889 Current anti-TNF use 204 (44) 137 (44) 67 (43) 0.733 Current NSAID use 230 (49) 149 (48) 81 (52) 0.491
Current DMARD use 32 (7) 23 (7) 9 (6) 0.490
BASDAI (0-10) 3.6 (0.0-9.6) 3.4 (0.0-9.4) 4.2 (0.2-9.6) 0.001 ASDASCRP 2.3 (0.4-5.7) 2.2 (0.4-5.2) 2.5 (0.6-5.7) 0.009 Patient GDA (0-10) 4 (0-10) 3 (0-10) 4 (0-10) 0.004
CRP (mg/l) 3 (0-94) 3 (0-94) 3 (0-82) 0.716
Swollen joint index (0-44) 0 (0-9) 0 (0-9) 0 (0-2) 0.702
≥1 swollen joint 17 (4) 12 (4) 5 (3) 0.703
Tender joint index (0-46) 0 (0-22) 0 (0-22) 0 (0-19) 0.012 ≥1 tender joint 107 (23) 60 (20) 47 (30) 0.013 BASFI (0-10) 3.4 (0.0-9.9) 3.1 (0.0-9.7) 4.0 (0.0-9.9) 0.037 ASQoL (0-18) 6 (0-18) 4 (0-18) 7 (0-18) 0.000
Values are presented as number of patients (%), mean ± SD or median (range).
* Male compared to female patients (Chi-square test, Independent samples t test or Mann-Whitney U test).
Abbreviations:SpA: spondyloarthritis; HLA-B27+: human leukocyte antigen B27 positive; IBD: inflammatory bowel disease; TNF: tumor necrosis factor; NSAID: non-steroidal anti-inflammatory drug; DMARD: disease-modifying antirheumatic drug; BASDAI: Bath AS disease activity index; ASDAS: AS disease activity score; GDA: global disease activity; CRP: C-reactive protein; BASFI: Bath AS functional index; ASQoL: AS quality of life.
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REFERENCES
1. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369:1379-1390.
2. Lee W, Reveille JD, Weisman MH. Women with ankylosing spondylitis: a review. Arthritis Rheum 2008;59:449-454.
3. Pinn WW. Sex and gender factors in medical studies: implications for health and clinical practice. JAMA 2003;289(4):397-400.
4. Schneider S, Stone AA. Distinguishing between frequency and intensity of health-related symptoms from diary assessments. J Psychosom Res. 2014;77:205-12.
5. Arends S, Brouwer E, van der Veer E, et al. Baseline predictors of response and discontinuation of TNF-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study. Arthritis Res Ther 2011;13:R94.
6. van der Horst-Bruinsma IE, Zack DJ, Szumski A, Koenig AS. Female patients with ankylosing spondylitis: analysis of the impact of gender across treatment studies. Ann Rheum Dis 2013;72:1221-1224.
7. Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011;70:896-904.
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SUPPLEMENTARY FILES
Supplementary Figure S1. Disease activity assessed with BASDAI (A), ASDAS (B), and CRP (C), physical function assessed with BASFI (D), and quality of life assessed with ASQoL (E) in male (n=309) and female (n=157) patients with axial SpA.
Box-and-whisker plots (Tukey): boxes indicate medians with interquartile ranges; whiskers indicate 1.5 times the interquartile distances; • indicate outliers. P-values represent differences between male and female patients (Mann-Whitney U test).
