Achilles Enthesitis on Physical Examination Leads to Worse Outcomes After 2 Years of Follow up in Patients With Ankylosing Spondylitis From REGISPONSER-AS Registry

Clementina López-Medina; M. Ángeles Puche-Larrubia; Raquel Granados; Lourdes Ladehesa-Pineda; Desirée Ruiz-Vilchez; M. Carmen Ábalos-Aguilera; Pilar Font-Ugalde; Eduardo Collantes-Estévez

Disclosures

Arthritis Res Ther. 2023;25(8)

Abstract and Introduction

Abstract

Background: Enthesitis represents one of the most important peripheral musculoskeletal manifestations in patients with axial spondyloarthritis (axSpA). However, studies specifically evaluating Achilles tendon enthesitis and its impact over time are scarce. The objectives of this study were to evaluate the impact of Achilles' tendon enthesitis found at baseline during physical examination on the outcome measures after 2 years of follow-up in patients with ankylosing spondylitis (AS).

Methods: This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. Linear regression models adjusted for age, body mass index (BMI), and anti-TNF intake were conducted to evaluate the association between the presence of Achilles enthesitis at baseline and the patient-reported outcome (PRO) scores at baseline. The impact of this feature on PROs over 2 years of follow-up was evaluated using mixed models for repeated measures adjusted for age, BMI, and anti-TNF intake.

Results: Among the 749 patients included, 46 patients (6.1%) showed Achilles' tendon enthesitis during physical examination at the baseline study visit. Patients with Achilles enthesitis had an increase in the global VAS score, BASDAI, mBASDAI, ASDAS-CRP, and BASFI scores in comparison with patients without this feature. In addition, the mean global VAS, BASDAI, and ASDAS-CRP scores were significantly higher among patients with Achilles enthesitis over the 2 years of follow-up after adjusting for age, BMI, and current anti-TNF intake. The percentage of patients achieving ASDAS low disease activity (ASDAS < 2.1) after 2 years of follow-up was 15.9% and 31.5% for patients with and without Achilles enthesitis, respectively (p = 0.030).

Conclusions: In patients with AS, the presence of Achilles' tendon enthesitis was associated with worse scores on the outcome measures after 2 years of follow-up, leading to a lower probability of achieving low disease activity.

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Arthritis Res Ther. 2023;25(8) © 2023 BioMed Central, Ltd.
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Abstract and Introduction
Background
Methods
Results
Discussion
Conclusions
References

Table 1. Baseline characteristics according to the presence of Achilles enthesitis
	Total N = 749	Current Achilles enthesitis N = 46	No current Achilles enthesitis N = 703	p-value
Sex (male)	564 (75.3%)	32 (69.6%)	532 (75.7%)	0.352
Age, mean (SD)	48.4 (12.3%)	47.8 (10.9)	48.4 (12.4)	0.759
BMI, mean (SD)	26.7 (4.3)	27.7 (4.9)	26.6 (4.2)	0.412
University studies	91/667 (13.6%)	5/45 (11.1%)	86/622 (13.8%)	0.608
Single	109/667 (16.3%)	7/45 (15.6%)	102/622 (16.4%)	0.883
Smoking (ever)	267/691 (53.1%)	17/41 (41.5%)	350/650 (53.8%)	0.123
Age of onset, mean (SD)	27.1 (10.3)	27.3 (13.2)	27.0 (10.1)	0.709
Disease duration, mean (SD)	21.4 (12.7)	20.5 (12.0)	21.5 (12.8)	0.726
Diagnosis delay, mean (SD)	8.1 (9.5)	7.6 (8.6)	8.1 (9.6)	0.786
Family history of SpA	420/701 (59.9%)	28/40 (70.0%)	392/661 (59.3%)	0.180
HLA-B27 positive	586/721 (81.3%)	37 (80.4%)	549/675 (81.3%)	0.880
Synovitis (ever)	250/748 (33.4%)	21 (45.7%)	229/702 (32.6%)	0.070
Psoriasis	82/746 (11.0%)	7 (15.2%)	75/700 (10.7%)	0.344
Inflammatory bowel disease	45 (6.0%)	2 (4.3%)	43 (6.1%)	1.000
Dactylitis	55/745 (7.4%)	6 (13.0%)	49/699 (7.0%)	0.141
Uveitis	154/745 (20.7%)	8 (17.4%)	146/699 (20.9%)	0.571
Swollen joints, mean (SD)	0.3 (1.6)	0.8 (1.7)	0.3 (1.6)	< 0.001
MASES score, mean (SD)	2.2 (1.9)	2.5 (1.9)	2.1 (1.9)	0.115
csDMARDs (ever)	155/742 (20.9%)	27/45 (37.8%)	138/697 (19.8%)	0.004
csDMARDs (current)	159/746 (21.3%)	18 (39.1%)	141/700 (20.1%)	0.002
Anti-TNF (ever)	261 (34.8%)	19 (41.3%)	242 (34.4%)	0.343
Anti-TNF (current)	157 (21.0%)	10 (21.7%)	147 (20.9%)	0.894
CRP mg/L, mean (SD)	9.2 (13.3)	11.0 (14.1)	9.1 (13.2)	0.870
ASDAS-CRP, mean (SD)	2.7 (1.1)	3.1 (1.2)	2.7 (1.0)	0.014
ASDAS low disease activity	206/681 (30.2%)	7/40 (17.5%)	199/641 (31.0%)	0.070
ASDAS inactive disease	66/681 (9.7%)	3/40 (7.5%)	63/641 (9.8%)	0.788
Global VAS (0–10), mean (SD)	4.6 (2.7)	5.9 (2.6)	4.6 (2.7)	0.001
BASDAI (0–10), mean (SD)	4.2 (2.4)	5.6 (2.2)	4.1 (2.3)	< 0.001
mBASDAI (0–10), mean (SD)	4.7 (2.5)	5.7 (2.3)	4.7 (2.5)	0.007
BASFI (0–100), mean (SD)	38.8 (27.3)	47.3 (27.6)	38.2 (27.2)	0.031
PC-SF12, mean (SD)	34.5 (11.6)	31.4 (11.8)	34.7 (11.6)	0.018
MC-SF12, mean (SD)	47.2 (13.8)	46.2 (15.3)	47.3 (13.7)	0.748
Total BASRI, mean (SD)	8.0 (4.0)	6.1 (3.0)	7.3 (4.01)	0.068

Anti-TNF anti-tumor necrosis factors, ASDAS-CRP Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, BASRI Bath Ankylosing Spondylitis Radiology Index, BMI body mass index, global VAS patient's global visual analog scale, CRP c-reactive protein, csDMARDs conventional synthetic disease-modifying antirheumatic drugs, mBASDAI modified Bath Ankylosing Spondylitis Disease Activity Index, MC-SF12 mental component from the SF-12 questionnaire, NSAIDs non-steroidal anti-inflammatory drugs, PC-SF12 physical component from the SF-12 questionnaire, SD standard deviation, SpA spondyloarthritis

Table 2. Association between current Achilles enthesitis and patient-reported outcomes at baseline
	Crude β coefficient (95%CI)^a Current Achilles vs. no current Achilles enthesitis	β coefficient (95% CI) adjusted^b Current Achilles vs. no current Achilles enthesitis
Global VAS	1.31 (0.50 to 2.11)	1.45 (0.60 to 2.31)
BASDAI	1.47 (0.77 to 2.17)	1.65 (0.92 to 2.38)
mBASDAI	1.01 (0.27 to 1.75)	1.23 (0.45 to 2.00)
ASDAS-CRP	0.44 (0.11 to 0.78)	0.58 (0.22 to 0.93)
BASFI	9.06 (0.93 to 17.20)	11.58 (3.48 to 19.68)
PC-SF12	− 3.28 (− 6.75 to 0.19)	− 4.23 (− 7.99 to − 0.47)
MC-SF12	− 1.07 (− 5.20 to 3.05)	− 1.45 (− 5.94 to 3.05)

^aLinear regression models
^bLinear regression models adjusted for age, body mass index and current anti-TNF
ASDAS-CRP Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, Global VAS patient's global visual analog scale, mBASDAI modified Bath Ankylosing Spondylitis Disease Activity Index, MC-SF12, mental component from the SF-12 questionnaire, PC-SF12 physical component from the SF-12 questionnaire

Table 3. Impact of the presence of Achilles enthesitis on patient-reported outcomes over two years of follow-up: mixed models for repeated measures
	Current Achilles enthesitis N = 46	No current Achilles enthesitis N = 703	Crude p-value	p-value adjusted*
Global VAS, mean (SD)	5.1 (2.8)	4.3 (2.6)	0.015	0.008
BASDAI, mean (SD)	4.8 (2.7)	3.9 (2.7)	< 0.001	< 0.001
mBASDAI, mean (SD)	5.2 (2.5)	4.5 (2.3)	< 0.001	0.005
ASDAS, mean (SD)	2.9 (1.1)	2.6 (1.0)	0.007	0.001
BASFI, mean (SD)	43.8 (29.7)	40.0 (27.4)	0.245	0.119
PC-SF12, mean (SD)	33.3 (11.4)	35.3 (10.7)	0.128	0.064
MC-SF12, mean (SD)	47.4 (14.2)	48.2 (12.2)	0.547	0.399

MMRM mixed model for repeated measures
*Adjusted for age, body mass index and current anti-TNF
ASDAS-CRP Ankylosing Spondylitis Disease Activity Score, BASDAI, Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, Global VAS, patient's global visual analog scale, mBASDAI modified Bath Ankylosing Spondylitis Disease Activity Index, MC-SF12 mental component from the SF-12 questionnaire, PC-SF12 physical component from the SF-12 questionnaire