Are we treating women patients with real axial spondyloarthritis?

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Are we treating women patients with real axial spondyloarthritis? Romina E. Nieto , Chamaida Plasencia Rodriguez , ´ ´ , Diana Peiteado Lopez , Alejandro Villalba Yllan ´ Alejandro Balsa Criado , Victoria Navarro-Compan PII: DOI: Reference:

S0049-0172(19)30699-7 https://doi.org/10.1016/j.semarthrit.2019.11.011 YSARH 51568

To appear in:

Seminars in Arthritis & Rheumatism

Please cite this article as: Romina E. Nieto , Chamaida Plasencia Rodriguez , ´ ´ , Diana Peiteado Lopez , Alejandro Villalba Yllan Alejandro Balsa Criado , ´ , Are we treating women patients with real axial spondyloarthritis?, Victoria Navarro-Compan Seminars in Arthritis & Rheumatism (2019), doi: https://doi.org/10.1016/j.semarthrit.2019.11.011

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Are We Treating Women Patients with Real Axial Spondyloarthritis?

Romina E. Nieto1, Chamaida Plasencia Rodriguez2, Diana Peiteado López2, Alejandro Villalba Yllán2, Alejandro Balsa Criado2, Victoria Navarro-Compán2

Author affiliations: 1

Hospital Provincial de Rosario, Rheumatology Department. Rosario, Argentina

2

University Hospital La Paz, IdiPaz, Rheumatology Department. Madrid, Spain

Corresponding author: Victoria Navarro Compán, MD, PhD. Rheumatology Department. University Hospital La Paz, IdiPaz. Pº de la Castellana, 261 – 28046 Madrid, Spain. E-mail: [email protected]

Abstract: Introduction: During the last years, regulatory agencies raised some relevant concerns with regard to the possibility of administrating biological therapy (BT) to non-SpA patients. Especially, the possibility of treating women with fibromyalgia as nonradiographic axSpA (nr-axSpA) was mentioned. Objectives: To evaluate if the gender distribution and clinical pattern of patients with axSpA initiating biological therapy (BT) was modified in clinical practice after its approval for non radiographic-axSpA (nr-axSpA). Methods: Baseline dataset from a prospective ongoing cohort including all patients with axSpA treated with BT at the Rheumatology Department of University Hospital La Paz, Madrid, Spain, was analysed. Patient’s characteristics and disease activity parameters were collected. Based on the approval indication date of BT for nr-axSpA, patients were classified in two periods according to the starting date for the first BT: period 1 (before 2013) and period 2 (during or after 2013). Gender distribution and disease’ characteristics were compared between both groups using Chi-square and Student-t tests.

Results: In total, 385 patients initiated BT: 266 (69%) in period 1 and 119 (31%) in period 2. No significant differences between both periods were observed regarding gender distribution (38% and 39% of women; p=0.8). Out of those patients with nraxSpA initiating BT in period 2, the majority (60%) were men. Women starting BT in period 2 had significantly higher systemic inflammation and mobility restriction compared with women in period 1 [median (interquartile range) CRP 10.2 mg/l (3.024.9) vs 3.2 mg/l (2.0-9.4); p=0.02 and BASMI 2.7 (1.8-3.5) vs 2.0 (1.2-2.6); p=0.01, respectively]. In addition, they also presented significantly higher disease activity [BASDAI 6.5 (5.4-8.0) vs 5.8 (4.6-6.8); p=0.02; ASDAS, mean (SD) 3.6 ±3.4 vs 3.2 ±1.0; p=0.02, respectively] and more functional limitation [BASFI 5.7 (3.8-6.7) vs 4.3 (2.06.1); p=0.01, respectively] than men treated in period 2. Conclusions: In our clinical practice, the frequency of women who started BT did not increase since their approval for nr-axSpA. Women treated with BT after 2012 had more objective disease activity parameters than before their approval for nr-axSpA treatment.

Keywords: Spondyloarthritis, non-radiographic axial Spondyloarthritis, TNF inhibitors, women, fibromyalgia.

Key messages: 1- Gender distribution and patients´ pattern were not changed since biological therapy was approved for nr-axSpA. 2- Most nr-axSpA patients who initiated biological therapy were men. 3- Women treated in recent years with biological therapy had more objective parameters of disease activity than men treated with the same therapy.

Introduction/background: During the last decade, the term spondyloarthritis (SpA) has evolved. Traditionally, this was employed to refer to a serie of chronic rheumatic disorders sharing common clinical manifestations and genetic association, with ankylosing spondylitis (AS) as the hallmark [1]. In recent years patients with SpA were usually classified according to the predominant clinical manifestations as axial or peripheral SpA. AxSpA is a general term that incorporates the classical AS and a newer entity, non-radiographic axSpA (nraxSpA). This new concept was coined as a consecuence of the Assessment of the Spondyloarthritis International Society (ASAS) SpA classification criteria development [2], incorporating those patients with axSpA who have a clinical picture of AS but do not exhibit radiographic sacroiliitis. Different cohorts have shown that nr-axSpA represent the same spectrum of the disease than the classical AS, with a similar burden of the disease [1]. In addition, different trials have shown a similar efficacy of biological

therapies, specifically tumour necrosis alpha inhibitors (TNFi), in patients with both axSpA subtypes. In 2012 the European Medicines Agency (EMA) approved the use of TNFi for patients with nr-axSpA. However, approximately one year later the United States Food and Drug Administration (FDA) raised some concerns related to this new indication and refused the approval of TNFi for nr-axSpA patients. Here, the major concern was the possible overdiagnosis of axSpA by physicians erroneously using the ASAS classification criteria to diagnose the disease, with the consequence of erroneous treatment decisions leading to the administration of TNFi to non-SpA patients, which are expensive and potentially hazardous medications [3]. In this context, the main question was the critique to the lack of specificity of the clinical arm of the ASAS criteria, and especially the possibility of overtreating women with fibromyalgia (FM). Historically, AS has been widely accepted as a male-predominant disease [4]. In the last years, most cohorts comparing patients with AS and nr-axSpA have shown a higher percentage of females among nr-axSpA patients. The persistent belief and lack of recognition of the clinical expression in females as well as a less severe disease course could justify the higher percentage of females observed within patients with nr-axSpA compared to AS [5, 6]. However, as state by some colleages, this could also be the result of an erroneously use of the ASAS classification criteria to diagnose axSpA in patients with FM, which is much more prevalent among women [7]. In clinical practice, FM is a confounding factor in rheumatic diseases in terms of both diagnosis and disease activity assessment. Distinguishing FM from rheumatic diseases can be challenging, particularly in nr-axSpA, since they share clinical characteristics such as generalized pain, mainly axial pain, fatigue and sleep disorders, as well as enthesitis painful sites that potentially overlap with the FM tender points [8]. Recently, Baraliakos et al analyzed the similarities and differences among patients diagnosed with axSpA and FM using different sets of criteria and several evaluations established with the objective of determining if patients with FM can be classified erroneously as having axSpA when applying ASAS criteria in clinical practice. Importantly, they observed that patients with FM rarely fulfil classification criteria for axSpA and, also, that patients with established AS fulfilled FM criteria more often than patients classified as nr-axSpA [9]. This study provided some light to clarify the concerns related to the possible overdiagnosis and overtreatment of patients with FM as a consequence of TNFi approval for nr-axSpA. However, no specific data regarding this concern are available yet. Accordingly, we decided to perform this study, with the main objective of evaluating if the gender distribution, pattern and clincial characteristics of patients with axSpA initiating TNFi have changed in clinical practice after the approval of this therapy for nr-axSpA.

Methods: Population and data collection Baseline dataset from SpA-PAZ cohort was analysed. This is a prospective ongoing cohort including all patients with axSpA according to Rheumatologist´diagnose treated with biological therapy (BT) since 2000 at the Rheumatology Department of University

Hospital La Paz in Madrid. At baseline, patients’ and disease’ characteristics were systematically collected. These characteristics included age, gender, smoking habit, disease duration, HLA-B27 carriership, peripheral involvement, extraarticular manifestations and current treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARD). Data were recorded on an electronic CRF but in the past data was first collected on paper CRF and patients´ medical records. In some cases, there were missing data in the database that had been collected either on paper CRF or patients' medical records. In addition, disease activity, functional status and mobility are were assessed by serum C-reactive protein (CRP) level (normal range ≤ 5 mg/l), visual analogue scales (VAS) for patient’s global assessment (PtGA mm), physician’s global assessment (PGA mm); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) –for disease activity-, Bath Ankylosing Spondylitis Function Index (BASFI) -for functional limitationand Bath Ankylosing Spondylitis Metrology Index (BASMI) –for mobility. Furthermore, physicians selected whether the patient has AS or nr-axSpA according to his/her criteria. Ax-SpA patients who received biological therapy because of the predominance of extra-axial manifestations were excluded. For this study, dataset was locked in August 2017. Data from all patients with axSpA starting a first TNFi were used for the analyses. The classification of axSpA (AS or nraxSpA) made by the treating physician at the moment of prescribing the TNFi therapy was employed. In case of doubt or missing data, one expert reader (VN-C) blinded to clinical data assessed the pelvic x-ray and evaluated the presence of radiographic sacroiliitis according to the modified New York criteria. The study was performed according with the declaration of Helsinki for the conduct of research in humans and following local institutional review boards regulations.

Statistical Analysis According to the treatment starting date with the first TNFi, patients were classified in two groups: Group 1 including patients starting TNFi before 2013 (period 1) and Group 2 including patients starting TNFi during or after 2013 (period 2). The reason to select this date was based on the approval date of TNFi for nr-axSpA in Spain. TNFi for nraxSpA were approved in July 2012 and for this analysis six extra months were added in order to allow enough time for implementation of this new prescription in clinical practice. Gender distribution, patients’ and disease’ characteristics were compared between both groups using Chi-square and Student-t tests or Wilcoxon when the corresponsing assumptions were not met. The results for descriptive data are presented by mean and standard deviation or median and interquartile range (IQR) depending on the normal distribution. All statistical analyses were performed employing SPSS (version 22, SPSS Inc.) and p values ≤ 0.05 were considered statistically significant.

Results: Study population period 1 versus study population period 2

In total, 385 patients with axSpA initiated TNFi therapy since 2000 till August-2017. Out of these, 266 (69%) patients initiated TNFi before 2013 (period 1) and 119 (31%) started this during or after 2013 (period 2). The characteristics of patients in both groups are depicted in table 1. No significant differences were observed between both periods with regard to the characteristics of patients when starting TNFi. Also, as shown in Figure 1, it is important to note that no differences were observed between both periods with respect to gender distribution (38% vs 39%; p=0.8). Regarding the distribution of SpA in period 2, a total of 61 patients (51%) were classified as nr-axSpA. On the other hand, 58 (49%) patients fulfilled New York criteria for AS. Furthermore, disease duration was numerically shorter in period 2, (median (IQR) 61 (18-143) months in period 1 and 51 (17-136) months in period 2) but this difference was not statistically significant. HLA B27 was performed in 371 patients of all evaluated patients. Of these, 229 (61.7%) were HLA-B27 positive and 142 (38.2%) were HLA-B27 negative. Female patients period 1 versus female patients period 2 Additionally, the characteristics of the female patients in period 1 were compared with the female patients in period 2 (table 2). The only statistically significant differences observed were that the females in period 2 had higher systemic inflammation and mobility restriction compared with the females in period 1 (median (IQR) CRP 10.2 (3.0-24.9) vs 3.2 (2.0-9.4); p=0.02 and BASMI 2.7 (1.8-3.5) vs 2.0 (1.2-2.6); p=0.01, respectively). Moreover, the ASDAS showed a trend to be significantly higher in female patients of period 2 (mean (SD) 3.6 ±3.4 vs 3.3 ±0.9; p=0.08). Male versus female patients period 2 A total of 72 males and 47 females initiated TNFi treatment during period 2. Out of those patients, 61 (51.3%) patients had nr-axSpA (59% males and 41% females). However, the percentage of patients with nr-axSpA was similar for both genders. Compared with males, the females in period 2 presented significantly higher disease activity (median (IQR) BASDAI 6.5 (5.4-8.0) vs 5.8 (4.6-6.8); p=0.02; ASDAS mean (SD) 3.6±3.4 vs 3.2 ±1.0; p=0.02, respectively) and more functional limitation (BASFI 5.7 (3.8-6.7) vs 4.3 (2.0-6.1); p=0.01, respectively) (table 2).

Discussion: This is the first study showing that the approval of TNFi for nr-axSpA by the EMA did not entail an overtreatment of women patients in clinical practice. Women treated nowadays with BT have more objective parameters of disease activity than they used to do before the indication for nr-axSpA was approved. These findings are relevant, especially in relation to the debate initiated in 2013, when the approval of TNFi for nraxSpA was denied by the FDA because of this concern [10]. On the one hand, the relative percentage of females and the gender distribution among axSpA patients who initiate TNFi has not changed since their approval for nraxSpA. In addition, the percentage of HLA-B27 carriers among females initiating BT has not increased overtime. HLA B27 was performed in 371 patients of all evaluated patients. Of these, 229 (61.7%) were HLA-B27 positive, which may be relatively low

compared with other cohorts. Nevertheless, these data were consistent with other registries including patients covering the whole spectrum of the disease axSpA initiating biological therapy such as the Swiss (SCQM) [11]. Moreover, the majority (51%) of patients with nr-axSpA who initiated TNFi were males. On the other hand, women treated nowadays with TNFi had more objective parameters of disease activity such as CRP compared with female patients treated with the same therapy before TNFi approval for nr-axspA. And also, they had more disease activity and worst functional limitation at baseline compared with male patients currently treated with this therapy. This probably reflects that, for prescribing a TNFi in clinical practice, physicians require more severe and active disease in female than male patients with axSpA, which may be precisely a consequence of physicians keeping in mind the concerns raised in the past around concomitant FM in females with nr-axSpA. Furthermore, as described in a previous study performed in the United Kingdom, this may also reflect that the diagnosis of SpA is not as easily reached in women as in men, and that the disease may therefore still be underdiagnosed or overlooked in women [5, 12]. In a national Registry (DANBIO) evaluating patients with axSpA starting treatment with TNFi, nr-axSpA patients were found to be more frequently women and have higher subjective disease activity parameters (such as visual analog scale scores for pain, fatigue, global and BASDAI) [13]. These findings differ from our study results, in which no differences with respect to gender distribution among nr-axSpa patients were observed and women presented more objective signs of disease activity at the start of first TNFi treatment. The fact that more than 20% of patients in the DANBIO Registry lacked radiographs of the sacroiliac joints could explain the differences observed between both studies. In contrast to EMA, the FDA, after the public hearing of the FDA Arthritis Advisory Committee Meeting in 2013, refused to approve the use of TNFi for patients identified as nr-axSpA [10]. In this context, the ASAS classification criteria were questioned since they could lead to an erroneous classification with the consequent excessive treatment in patients with chronic back pain and FM. In this sense, a recent study performed in Germany has shown that patients with FM rarely fulfil classification criteria for axSpA and, also, that patients with established AS fulfilled FM criteria more often than patients classified as nr-axSpA [9]. In addition to these data, our study supports the hypothesis that, if the ASAS classification criteria are correctly employed, the approval of BT for nr-axSpA by regulatory agencies does not imply the misdiagnosis and overtreatment of female patients with FM. Nevertheless, this study has some limitations. A potential weakness may be that despite most of the data was prospectively recorded some missing data were collected retrospectively and we do not perform FM systematic research in ax-SpA patients. Moreover, the relative small sample and the fact that all data represent the clinical practice of a unique center may have influenced the analysis and results of the study. In this sense, due to the limit sample size, the stratified gender analysis for nr-axSpA could not be performed. In addition, the only type of BT evaluated in this study was TNFi and therefore these results cannot be extrapolated to other BT such as IL-17 inhibitors. Finally, the response to the biological therapy was not analyzed in this opportunity and would be of interest for the future.

In summary, the results of this study show how gender distribution and pattern of axSpA patients did not change in clinical practice since TNFi was approved for nraxSpA. Despite broadening the spectrum of patients with axSpA treated with BT, the frequency of females receiving this type of therapy has remained similar overtime. Furthermore, the majority of patients with nr-axSpA under TNFi were males. Additionally, women treated nowadays with TNFi have more objective disease activity parameters than they used to have (before TNFi approval for nr-axSpA) and also than men currently treated with TNFi. This supports that when treating axSpA women (including nr-axSpA) with BT, we are currently treating real axSpA -and not FMpatients. Diagnosis of axSpA should be based on a complex process involving pattern recognition and clinical reasoning by a skilled and experienced physician and classification criteria should serve as a different purpose to select patients for studies. If applied correctly, the ASAS criteria do not lead to an overtreatment in patients with axSpA [14]. Nevertheless, in order to confirm these results, additional studies involving multicentric and larger samples are necessary.

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3. 4. 5.

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7. 8. 9. 10. 11.

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Braun, J. and J. Sieper, Ankylosing spondylitis. Lancet, 2007. 369(9570): p. 1379-1390. Rudwaleit, M., et al., The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis, 2009. 68(6): p. 777-83. van der Heijde, D., et al., 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis, 2017. 76(6): p. 978-991. Polley, H.F. and C.H. Slocumb, Rheumatoid spondylitis; a study of 1,035 cases. Ann Rheum Dis, 1947. 6(2): p. 95-8. Roussou, E. and S. Sultana, Spondyloarthritis in women: differences in disease onset, clinical presentation, and Bath Ankylosing Spondylitis Disease Activity and Functional indices (BASDAI and BASFI) between men and women with spondyloarthritides. Clin Rheumatol, 2011. 30(1): p. 121-7. Rusman, T., R.F. van Vollenhoven, and I.E. van der Horst-Bruinsma, Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky. Curr Rheumatol Rep, 2018. 20(6): p. 35. Deodhar, A., Axial spondyloarthritis criteria and modified NY criteria: issues and controversies. Clin Rheumatol, 2014. 33(6): p. 741-7. Fan, A., et al., Frequency of concomitant fibromyalgia in rheumatic diseases: Monocentric study of 691 patients. Semin Arthritis Rheum, 2017. 47(1): p. 129-132. Baraliakos, X., et al., Patients with fibromyalgia rarely fulfil classification criteria for axial spondyloarthritis. Rheumatology (Oxford), 2018. 57(9): p. 1541-1547. Axial Spondyloarthritis: Regulatory Considerations on its use as an Indication for Drug Development. FDA Arthritis Advisory Committee Meeting. 2013. . Ornbjerg, L.M., et al., Treatment response and drug retention rates in 24 195 biologicnaive patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration. Ann Rheum Dis, 2019. Jovani, V., et al., Understanding How the Diagnostic Delay of Spondyloarthritis Differs Between Women and Men: A Systematic Review and Metaanalysis. J Rheumatol, 2017. 44(2): p. 174-183. Glintborg, B., et al., Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry. J Rheumatol, 2017. 44(1): p. 59-69. Rudwaleit, M., Fibromyalgia is not axial spondyloarthritis. Rheumatology (Oxford), 2018. 57(9): p. 1510-1512.

Tabla 1- Characteristics of all patients included in the study, stratified by the period in which the first TNFi was initiated.

2000-2012 n=266

2013-2017 n=119

-

61(51)

43.7 (11.9)

45.1 (14.1)

0.3

117 (44)

58 (49)

0.4

61 (18-143)

51 (17-136)

0.8

161(60)

68(57)

0.5

6.0 (4.9-7.2)

6.0 (4.7-7.1)

0.9

3.3 (0.9)

3.4 (1.0)

0.5

BASFI median (IQR)

5.0 (3.0-6.8)

4.7 (2.6-6.4)

0.3

BASMI median (IQR)

2.1 (1.4-3.6)

2.4 (1.6-3.6)

0.4

CRP mg/l median (IQR)

4.1 (2.3-12.4)

7.5 (1.8-18.5)

0.1

Elevated CRP mg/l n (%)

120 (45)

72 (61)

0.01

Nr-axSpA n (%) Age, years mean (SD) Smokers’ n (%) Disease duration, months, median (IQR) a

HLA-B27 positive n (%) BASDAI median (IQR) ASDAS mean (SD) n=303

p value

Spinal Pain mm median (IQR) 70.0 (50.0-80.0)

70.0 (50.0-80.0)

0.2

(BASDAI question2) PtGA mm median (IQR)

69 (50.0-80.0)

70 (50.0-80.0)

0.1

PGA mm median (IQR)

45 (20.0-60.0)

45 (30.0-60.0)

0.3

Peripheral involvement n (%)

115 (43)

57 (48)

0.4

csDMARD n (%)

129 (49)

61 (51)

0.6

TNFi: tumour necrosis factor inhibitor; nr-axSpA: nonradiographic axSpA; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; ASDAS: Ankylosing Spondylitis Disease Activity Score; BASFI: Bath Ankylosing Spondylitis Function Index; BASMI: Bath Ankylosing Spondylitis Metrology Index; CRP: Creactive protein; Elevated CRP ≥5mg/l; PGA: physician’s global assessment; PtGA: patient’s global assessment; csDMARD: synthetic disease-modifying antirheumatic drugs (Methotrexate, Sulfasalazine a and Leflunomide). HLA-B27 was available in 371/385 patients. Results are shown as median (interquartile range) unless otherwise is specified.

Tabla 2- Characteristics of all patients included in the study, stratified by gender and the period in which the first TNFi was initiated.

Period 1 Period 1 2000-2012

Period 2 Period 2 2013-201717

p value

Period 1 2000-2012

Period 2 2013-2017

p value

Males n=164

Females n=102

Males n=72

Females n=47

Females period 1 vs 2

Females vs Males Period 2

43.7 (11.4)

43.6 (12.8)

43.9 (13.8)

47.0 (14.5)

0.2

0.2

77 (46.9)

40 (39.2)

34 (47.2)

24 (51.1)

0.2

0.7

Disease duration, months median (IQR)

63.5 (20.0156.5)

55.5 (15.0133.0)

62.5 (18.0157.5)

49.0 (15.0121.0)

0.9

0.3

HLA-B27 positivea n (%)

106 (64.6)

55 (53.9)

41 (56.9)

27 (57.4)

0.3

0.9

5.7 (4.3-6.8)

6.9 (5.5-7.9)

5.8 (4.6-6.8)

6.5 (5.4-8.0)

0.5

0.02

3.3 (1.0)

3.3 (0.9)

3.2 (1.0)

3.6 (3.4)

0.08

0.02

BASFI median (IQR)

4.9 (2.6-6.4)

5.3 (4.0-7.0)

4.3 (2.0-6.1)

5.7 (3.8-6.7)

0.9

0.01

BASMI median (IQR)

2.4 (1.6-4.0)

2.0 (1.2-2.6)

2.2 (1.6-3.8)

2.7 (1.8-3.5)

0.01

0.6

4.3 (2.6-14.7)

3.2 (2.0-9.4)

6.8 (1.5-18.5)

10.2 (3.0-24.9)

0.02

0.3

77 (64)

43 (36)

40 (56)

32 (44)

0.24

0.2

70.0 (43.080.0)

70.0 (50.080.0)

70.0 (40.080.0)

70.0 (60.090.0)

0.05

0.1

PtGA mm median (IQR)

67 (50.0-80.0)

70 (50.0-80.0)

70 (50.0-80.0)

70 (50.0-80.0)

0.4

0.6

PGA mm median (IQR)

40 (20.0-60.0)

50 (20.0-60.0)

40 (30.0-60.0)

45 (30.0-60.0)

0.6

0.3

Peripheral involvement n (%)

57 (34.7)

58 (56.9)

33 (45.8)

24 (51.1)

0.5

0.6

csDMARD n (%)

77 (46.9)

52 (50.9)

33 (45.8)

28 (59.6)

0.3

0.1

Nr-axSpA n (%)

-

-

36 (50.0)

25 (53.2)

-

0.7

Age, years mean (SD) Smokers’ n (%)

BASDAI median (IQR) ASDAS mean (SD) n=303

CRP mg/l median (IQR) Elevated CRP mg/l n (%) Spinal Pain mm median (IQR) (BASDAI question2)

TNFi: tumour necrosis factor inhibitor; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; ASDAS: Ankylosing Spondylitis Disease Activity Score; BASFI: Bath Ankylosing Spondylitis Function Index; BASMI: Bath Ankylosing Spondylitis Metrology Index; CRP: C-reactive protein; Elevated CRP ≥5mg/l; PGA: physician’s global assessment; PtGA: patient’s global assessment; csDMARD: synthetic diseasemodifying antirheumatic drugs (Methotrexate, Sulfasalazine and Leflunomide); nr-axSpA: a nonradiographic axSpA. HLA-B27 was available in 371/385 patients Results are shown as median (interquartile range) unless otherwise is specified.