Extra-musculoskeletal manifestations driving the therapeutic decision-making in patients with Spondyloarthritis: a 12-month follow-up prospective cohort study

Annunciato, Danielle dos Reis; Oliveira, Thauana Luiza; Magalhães, Vanessa Oliveira; Pinheiro, Marcelo de Medeiros

doi:10.1186/s42358-023-00324-0

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Sumário

Research • Adv. rheumatol. 63 • 2023 • https://doi.org/10.1186/s42358-023-00324-0 copy

Extra-musculoskeletal manifestations driving the therapeutic decision-making in patients with Spondyloarthritis: a 12-month follow-up prospective cohort study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

The extra-musculoskeletal manifestations (EMMs) such as recurrent acute anterior uveitis (rAAU), psoriasis (Ps), and inflammatory bowel disease (IBD), are related to the Spondyloarthritis (SpA), as well as they are associated with disease activity and poor prognosis. However, there are no data addressing its relevance regarding therapeutic decision-making in clinical practice.

Objective

To evaluate the impact of EMMs to drive the treatment decision-making in patients with SpA in a 12-month follow-up.

Patients and methods

SpA patients, according to the axial and peripheral ASAS classification criteria, as well as CASPAR criteria, with any active EMM, defined as main entry criteria, were included in this longitudinal cohort study. Individuals with a history of any disease or condition that could be associated with some of the studied endpoints, including neoplasms and infectious diseases, were excluded. Specific tools related to each EMM, including Psoriasis Area Severity Index (PASI), ophthalmologic evaluation, according to the Standardization of Uveitis Nomenclature (SUN) criteria, and gut complaints were used at baseline and during the 3-, 6- and 12-month of follow-up as outcomes measures over time. Descriptive and inferential analyses were used appropriately, including Pearson’s correlation test, chi-squared test, and ANOVA. P value less than 0.05 was considered as significant.

Results

A total of 560 patients were enrolled, of whom 472 meet the eligibility criteria. The majority (N = 274; 59.6%) had one or more EMM related to SpA umbrella concept. Among the EMM, the one that most influenced therapeutic decision-making was psoriasis (28.5%), followed by uveitis (17.5%) and IBD (5.5%), regardless of musculoskeletal manifestations. Clinical improvement of EMMs outcomes was observed in most patients over 12-month follow-up, especially in those with rAAU and IBD (P < 0.001).

Conclusion

Our results showed that EMMs guided the therapeutic decision-making in half of SpA patients, regardless of musculoskeletal condition, suggesting the inter-disciplinarity among the rheumatologist, ophthalmologist, dermatologist, and gastroenterologist plays a crucial role to manage them.

Keywords
Spondyloarthritis; Extramusculoskeletal manifestations; Uveitis; Psoriasis; Inflammatory bowel disease; Treatment; Decision-making; Longitudinal cohort

Variable		rAAU (N = 48)	Psoriasis (N = 78)	IBD (N = 15)	^p
Male, n (%)		29 (60.4%)	48 (61.5%)	7 (46.7%)	0.55
Age (Years)		49.1 (12.1)	57.8 (14.5)	47.9 (14.8)	0.001
Skin color
	White, n (%)	27 (56.3%)	51 (65.4%)	10 (66.7%)	0.46
	Non-white, n (%)	21 (43.7%)	24 (30.8%)	5 (33.3%)
	Unknown, n (%)	0	3 (3.8%)	0
Time of disease (years)		18.7 (9.6)	22.6 (	13 (8.1)	0.01
Family History of SpA, n (%)		11 (22.9%)	12 (15.4%)	1 (6.7%)	0.29
DAIAGNOSTIC DELAY (years)		11.8 (9.4)	15.9 (12.4)	5.7 (5.9)	0.001
Current smoking, n (%)		4 (8.3%)	13 (16.7%)	1 (6.7%)	0.3
Positivity for HLA-B27, n (%)		33 (68.8%)	5 (6.4%)	5 (33.3%)	< 0.0001
Axial predominance, n (%)		15 (31.2%)	1 (1.3%)	3 (20%)	< 0.0001
Peripheral predominance, n (%)		1 (2.1%)	28 (35.9%)	2 (13.3%)	< 0.0001
Comorbidities Fibromyalgia, n (%)		6 (12.5%)	7 (9%)	2 (13.3%)	0.77
Low BMD for age, n (%)		10 (20.8%)	18 (23.1%)	6 (40%)	0.30

Variable	Baseline	3 months	6 months	12 months	^p
Active rAAU, n (%)	48 (100%)	11 (22.9%)	10 (20.8%)	7 (14.6%)	< 0.001
Active Psoriasis N (%)	78 (100%)	55 (70.5%)	48 (57.7%)	40 (51.3%)	< 0.001
PASI	11.1 (10.5)	6.9 (8.2)	7.8 (11.6)	3.4 (5.6)	< 0.001
Active ibd, N (%)	78 (100%)	55 (70.5%)	48 (57.7%)	40 (51.3%)	< 0.0001
Diarrhea episodesmean/day	5.2 (3.0)	3.3 (4.1)	1.6 (3.0)	1.5 (3.0)	< 0.001
Blood or mucus in stools, n (%)	6 (40%)	6 (40%)	3 (20%)	2 (13.3%)	0.08
Abdominal Pain, n (%)	6 (40%)	6 (40%)	3 (20%)	2 (13.3%)	0.003

EMM		Baseline	3 months	6 months	12 months	^p
	Remission or inactive disease (ASDAS < 1.3)
	rAAU, n (%)	12 (26.7%)	14 (32.6%)	13 (31.7%)	12 (31.5%)	0.92
	Psoriasis, n (%)	10 (17.2%)	9 (17.3%)	10 (19.6%)	11 (22%)	0.7
IBD, n (%)		0	1 (6.7%)	2 (13.3%)	1 (6.7%)	0.07
Low disease activity (1.3 ≤ ASDAS < 2.1)
	rAAU, n (%)	6 (13.3%)	8 (18.6%)	11 (26.8%)	7 (18.4%)	0.23
	Psoriasis, n (%)	9 (15.5%)	6 (11.5%)	19 (37.2%)	17 (34%)	0.08
	IBD, n (%)	1 (7.1%)	3 (20%)	4 (26.7%)	5 (33.3%)	0.27
High or very high disease activity (ASDAS ≥ 2.1)
	rAAU, n (%)	27 (60%)	21 (48.8%)	17 (41.4%)	19 (50%)	0.08
	Psoriasis, n (%)	39 (67.2%)	37 (71.1%)	22 (43.1%)	22 (44%)	0.02
	IBD, n (%)	13 (92.8%)	10 (66.6%)	9 (60%)	9 (60%)	0.06

EmM	Baseline	3 months	6 months	12 months	^p
Active rAAU, n (%)	48 (100%)	11 (22.9%)	10 (20.8%)	7 (14.6%)	< 0.001
DECISION-MAKING^* * Regarding the number of patients that still had an active EAM , N (%)	48 (100%)	10 (91%)	9 (90%)	7 (100%)	< 0.001
ACTIVE PS, N (%)	78 (100%)	55 (70.5%)	45 (57.7%)	40 (51.3%)	< 0.001
DECISION-MAKING^* * Regarding the number of patients that still had an active EAM , N (%)	78 (100%)	30 (54.5%)	26 (57.8%)	14 (35%)	< 0.0001
ACTIVE IBD, N (%)	14 (93.3%)	8 (53.3%)	4 (26.7%)	4 (26.7%)	< 0.001

Medications	Previous (N = 78)	Baseline (N = 78)	3 months (N = 55)	6 months (N = 48)	12 months (N = 40)	^p
No medication, n (%)	23 (29.5%)	0	0	0	0
Topic Glucocorticoid, n (%)	13 (16.7%)	8 (10.3%)	6 (10.9%)	8 (16.7%)	4 (10%)	0.07
Oral systemic Glucocorticoids, n (%)	6 (7.7%)	3 (3.8%)	1 (1.9%)	1 (2.1%)	1 (2.5%)	0.26
DMARDs, n (%)	43 (55.1%)	68 (87.2%)	28 (50.9%)	21 (43.8%)	12 (30%)	< 0.0001
MTX, n (%)	27 (34.6%)	25 (32.1%)	9 (16.4%)	8 (16.7%)	5 (12.5%)	< 0.0001
LEF, n (%)	9 (11.5%)	3 (3.8%)	5 (9.1%)	6 (12.5%)	2 (5.0%)	0.001
SSZ, n (%)	1 (1.3%)	5 (6.4%)	0	0	0	0.07
CsA, n (%)	3 (3.8%)	4 (5.1%)	7 (12.7%)	5 (10.4%)	3 (7.5%)	0.71
MTX + CsA, n (%)	1 (1.3%)	5 (6.4%)	0	2 (4.2%)	0	0.24
MTX + LEF, n (%)	1 (1.3%)	7 (9.0%)	5 (9.1%)	0	2 (5.0%)	0.009
LEF + CsA, n (%)	1 (1.3%)	42 (53.8%)	2 (3.6%)	0	0	0.002
Biological agents, n (%)	11 (14.1%)	37 (47.4%)	18 (32.7%)	24 (50%)	12 (30%)	< 0.0001
TNF inhibitors, n (%)	10 (12.8%)	17 (21.8%)	17 (30.9%)	16 (33.3%)	9 (22.5%)	< 0.0001
Adalimumab, n (%)	6 (7.7%)	1 (1.3%)	9 (16.4%)	9 (18.8%)	2 (5.0%)	0.08
Golimumab, n (%)	1 (1.3%)		0	2 (4.17%)	2 (5.0%)	0.64
Etanercept, n (%)	0	13 (16.7%)	7 (12.7%)	2 (4.17%)	3 (7.5%)	< 0.0001
Infliximab, n (%)	3 (3.8%)	8 (10.3%)	1 (1.9%)	5 (10.4%)	0	0.07
Abatacept, n (%)	0	1 (1.3%)	0	1 (2.8%)	0	0.56
Ustekinumab, n (%)	1 (1.3%)	2 (2.6%)	1 (1.9%)	1 (2.8%)	2 (5.0%)	0.95
SECUKINUMAB, N (%)	0	0	0	4 (8.3%)	0	0.003

Medications	Previous (N = 78)	Baseline (N = 78)	3 months (N = 55)	6 months (N = 48)	12 months (N = 40)	^p
No medication, n (%)	23 (29.5%)	0	0	0	0
Topic Glucocorticoid, n (%)	13 (16.7%)	8 (10.3%)	6 (10.9%)	8 (16.7%)	4 (10%)	0.07
Oral systemic Glucocorticoids, n (%)	6 (7.7%)	3 (3.8%)	1 (1.9%)	1 (2.1%)	1 (2.5%)	0.26
DMARDs, n (%)	43 (55.1%)	68 (87.2%)	28 (50.9%)	21 (43.8%)	12 (30%)	< 0.0001
MTX, n (%)	27 (34.6%)	25 (32.1%)	9 (16.4%)	8 (16.7%)	5 (12.5%)	< 0.0001
LEF, n (%)	9 (11.5%)	3 (3.8%)	5 (9.1%)	6 (12.5%)	2 (5.0%)	0.001
SSZ, n (%)	1 (1.3%)	5 (6.4%)	0	0	0	0.07
CsA, n (%)	3 (3.8%)	4 (5.1%)	7 (12.7%)	5 (10.4%)	3 (7.5%)	0.71
MTX + CsA, n (%)	1 (1.3%)	5 (6.4%)	0	2 (4.2%)	0	0.24
MTX + LEF, n (%)	1 (1.3%)	7 (9.0%)	5 (9.1%)	0	2 (5.0%)	0.009
LEF + CsA, n (%)	1 (1.3%)	42 (53.8%)	2 (3.6%)	0	0	0.002
Biological agents, n (%)	11 (14.1%)	37 (47.4%)	18 (32.7%)	24 (50%)	12 (30%)	< 0.0001
TNF inhibitors, n (%)	10 (12.8%)	17 (21.8%)	17 (30.9%)	16 (33.3%)	9 (22.5%)	< 0.0001
Adalimumab, n (%)	6 (7.7%)	1 (1.3%)	9 (16.4%)	9 (18.8%)	2 (5.0%)	0.08
Golimumab, n (%)	1 (1.3%)		0	2 (4.17%)	2 (5.0%)	0.64
Etanercept, n (%)	0	13 (16.7%)	7 (12.7%)	2 (4.17%)	3 (7.5%)	< 0.0001
Infliximab, n (%)	3 (3.8%)	8 (10.3%)	1 (1.9%)	5 (10.4%)	0	0.07
Abatacept, n (%)	0	1 (1.3%)	0	1 (2.8%)	0	0.56
Ustekinumab, n (%)	1 (1.3%)	2 (2.6%)	1 (1.9%)	1 (2.8%)	2 (5.0%)	0.95
SECUKINUMAB, N (%)	0	0	0	4 (8.3%)	0	0.003

Medications	Previous (N = 14)	Baseline (N = 14)	3 months (N = 8)	6 months (N = 4)	12 months (N = 4)	^p
No medication, n (%)	4 (26.7%)	0	0	0	0
Oral Glucocorticoid, n (%)	3 (20%)	3 (20%)	2 (25%)	2 (50%)	1 (25%)	0.84
DMARDs, n (%)	3 (20%)	12 (60%)	5 (62.5%)	1 (25%)	3 (75%)	< 0.0001
AZA, n (%)	0	4 (26.7%)	1 (12.5%)	1 (25%)	2 (50%)	0.16
SSZ, n (%)	3 (20%)	8 (53.3%)	3 (37.5%)	0	1 (25%)	0.007
Mesalazine, n (%)	0	0	1 (12.5%)	0	0	0.41
Biologic agents, n (%)	6 (40%)	11 (73.3%)	5 (62.5%)	2 (50%)	3 (75%)	< 0.0001
Adalimumab, n (%)	2 (13.3%)	4 (26.7%)	3 (37.5%)	0	1 (25%)	0.08
Golimumab, n (%)	1 (6.7%)	1 (6.7%)	0	0	1 (25%)	0.63
Etanercept, n (%)	1 (6.7%)	0	0	0	0	0.41
Infliximab, n (%)	2 (13.3%)	2 (13.3%)	1 (12.5%)	1 (25%)	1 (25%)	0.60
Certolizumab, n (%)	0	0	1 (12.5%)	0	0	0.04
Ustekinumab, n (%)	0	0	0	1 (25%)	0	0.41

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[1] *Correspondence: Marcelo de Medeiros Pinheiro mpinheiro@uol.com.br