# Article published Joint Bone Spine Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis

Caroline Pignon, Noémie Bibas, Clementina Lopez-Medina, Bruno Fautrel, Laure Gossec

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## ► To cite this version:

Caroline Pignon, Noémie Bibas, Clementina Lopez-Medina, Bruno Fautrel, Laure Gossec. Article published Joint Bone Spine Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis. Joint Bone Spine, 2025, 92 (2), pp.105807. 10.1016/j.jbspin.2024.105807. hal-05002802

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Submitted on 24 Mar 2025

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## Article published Joint Bone Spine

**Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis.**

**Authors**

Caroline Pignon<sup>1,2</sup>, Noémie Bibas<sup>1,2</sup>, Clementina Lopez-Medina<sup>1,2,3</sup>, Bruno Fautrel<sup>1,2</sup>, Laure Gossec<sup>1,2</sup>

**Affiliations**

<sup>1</sup>Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, 75013 Paris, France.

<sup>2</sup>Rheumatology Unit, Pitié-Salpêtrière University Hospital, AP-HP, 75013 Paris, France.

<sup>3</sup>Rheumatology Department, Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain.

**ORCIDs**

Caroline Pignon: 0009-0000-1205-5859

Noémie Bibas 0009-0007-0494-4884

Clementina Lopez-Medina: 0000-0002-2309-5837

Bruno Fautrel: 0000-0001-8845-4274

Laure Gossec: 0000-0002-4528-310X

**Corresponding author:**

Caroline Pignon, Hôpital Pitié-Salpêtrière, Service de Rhumatologie, 47-83, boulevard de l'Hôpital - 75013 Paris France

Caroline.pignon@aphp.fr +33142178421

**Word count** 2460 words

**Figures and tables:** 4 tables, 2 figures

**Keywords:** Psoriatic arthritis, enthesitis, prevalence, epidemiology, assessment, Achilles tendon

**Key messages:**

* In psoriatic arthritis, clinical enthesitis is present in 41.6% patients.

* Prevalence of enthesitis is higher in clinical trials than in observational studies.

* The Leeds enthesitis index (LEI) is the most-used score.

* The LEI may lead to under-estimation of enthesitis.

* Enthesitis is associated with higher disease activity.
**Abstract (249 words)**

**Objectives:** Enthesitis is considered a hallmark of psoriatic arthritis (PsA). The objective was to assess clinical enthesitis in PsA including its prevalence in different contexts, scores used and consequences of enthesitis.

**Methods:** A systematic literature review with meta-analysis was conducted in PubMed 2010-2023, focusing on manuscripts involving adult PsA patients and reporting information related to enthesitis. Data collected included the prevalence of clinical enthesitis (i.e., number of patients with at least one enthesitis); scores used: Leeds Enthesitis Index (LEI), MASES, SPARCC; and impact of enthesitis on disease activity, patient-reported outcomes and use of analgesics. Univariate random-effects meta-analysis was applied for pooling percentages and means.

**Results:** Overall, 212 studies, i.e., 84,262 PsA patients were analyzed. The pooled prevalence of enthesitis in the overall population was 41.6% [95% confidence interval, 37.4-45.8]; with 67.2% [62.0-72.6] in trials and 27.8% [24.5-31.2] in observational studies. The number of enthesitis varied according to the score used, with the lowest observed for the LEI which was the most widely-used score (63.7%). Patients with enthesitis had higher disease activity and disease burden in comparison with those without enthesitis.

**Conclusion:** Enthesitis is a frequent manifestation in PsA, concerning close to half the patients, and is more prevalent in trials than in observational studies, reflecting recruitment patterns. The clinical assessment of enthesitis remains challenging, with heterogeneity in the scores used influencing the results: the most used score was the LEI which also led to the lowest prevalence of enthesitis. Links with patients' quality of life should be further explored.

# 1 Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by heterogenous musculoskeletal and non-musculoskeletal manifestations, such as peripheral synovitis, enthesitis, dactylitis, and axial inflammation. These manifestations lead to impaired function and reduced quality of life, including sleep disturbances, decreased work capacity, and social isolation.(1)

Enthesitis is usually considered a hallmark manifestation of PsA.(2) Enthesitis refers to inflammation of the enthesis and is seen in both PsA and axial spondyloarthritis (axSpA).(1) Enthesitis is considered as the primary event in PsA.(3) Detection of enthesitis may contribute to the diagnosis of PsA, and indeed, is part of the Classification Diagnostic for Psoriatic Arthritis (CASPAR), reflecting the importance of this manifestation.(4,5) Diagnostic criteria of PsA have changed some years ago thus recent studies of PsA may bring to light different findings compared to older studies. Furthermore, studies focused on enthesitis are rare.

Enthesitis has been reported as frequent in PsA patients; however, the prevalence covers a wide range across articles, with values between 6% and 72%.(6–8) Furthermore, the number of entheses involved in a given patient is not well known. In trials, patients often present with multiple enthesal sites.(9) This may differ in clinical practice.

Enthesitis is clinically detected by pressure at the insertion of a tendon or ligament into the bone. Several scores are used for enthesitis, including the Leeds Enthesitis Index (LEI) measuring 6 peripheral entheses, the SpondyloArthritis Research Consortium of Canada (SPARCC) assessing 16 sites and the Maastricht Ankylosing Spondylitis Enthesitis score (MASES) evaluating 13 entheses of which 11 are axial.(6,10–13) A study from 2018 reported that the LEI seemed to be the most commonly-used score, followed by the SPARCC and MASES.(2) However, as new studies and trials are performed, it would be interesting to know how this evolved in recent studies. The score used may also influence the number of entheses considered inflamed, since scores do not assess the same localizations in the
body. It would be interesting for the clinician to know which sites to prioritize when examining a patient. The most frequently-affected site appears to be the Achilles tendon, however this should be confirmed.(14,15)

The consequences of enthesitis may include increased disease activity (including arthritis, extent of psoriasis or dactylitis) and decreased quality of life; potential associations with poor prognosis e.g. depression, sick leave, treatment consumption, have been little explored.(1–3,15–18) It would also be interesting to explore the potential association with fibromyalgia or widespread pain syndrome since the clinical aspects can be quite close.(19,20)

The aim of this study was to assess the frequency of clinical enthesitis in PsA, scores used and their potential effects on the frequency measured, most affected localizations, and the impact of enthesitis on disease activity and on patients' quality of life.

## 2 Methods

We conducted a systematic review of the literature with meta-analysis. The Cochrane guidelines were followed.(21,22) PRISMA checklist is available in supplementary table 3.

### 2.1 Data sources

A search strategy was designed to identify recent scientific publications that report information on enthesitis. The datasource was PubMed and we did not explore other datasources since most clinical studies in PsA are available in PubMed.(23) The search was performed on papers published between January 2010 and June 2023; the date of 2010 was chosen since the concept of PsA may have evolved following the publication of the CASPAR criteria in 2006.(4)

The articles were selected based on keywords reflecting PsA and enthesese involvement (listed below), with no restrictions on study type or on quality. Keywords were ("psoriatic arthritis" [title/abstract] OR PsA [title/abstract] OR psoriatic arthropath*[title/abstract]) AND ("enthesopathy" [MeSH Terms] OR "Enthesopathy" or "enthesitis").

Inclusion criteria were original articles involving human subjects aged ≥18 years, a diagnosis of PsA whatever the criteria used, and reporting any information on enthesitis. The information could include frequency, scores used, characteristics of enthesitis and/or consequences. Studies could be randomized controlled trials (RCTs) or observational studies, published in English. Studies on spondyloarthritis or axial spondyloarthritis (axSpA) were excluded if they did not specifically discuss PsA. Trials were included if they provided information on enthesitis at baseline.

The selection was performed on the Rayyan platform, first on abstracts then on full texts.(24) Article selection was performed by one reviewer for abstracts. For the second screening on the full texts, data of 12.6% of the articles were collected by two reviewers (CP and NB). During the screening process, a manual search resulted in the inclusion of 12 additional studies.

### 2.2 Data extraction

Data extraction was based on full texts, using a reading grid designed specifically for this meta-analysis. We analyzed the baseline time point of interventional studies and the first time point in longitudinal observational studies.

The quality of the papers was not assessed due to the heterogeneity of the study designs.

### 2.3 Data collected

General data about the articles were recorded. Population information was collected, such as age, sex, weight, ethnic origin, and the frequency of fibromyalgia or widespread pain, as reported (i.e., according to physical examination or questionnaires). The data were collected in the whole population and those with enthesitis specifically.
### 2.3.1 Prevalence

Enthesitis frequency was collected through the number of patients having at least one enthesitis among PsA patients, and according to the different scores. The mean number of enthesitis per patient affected by enthesitis was also collected.

Prevalence of enthesitis was collected for each score. When multiple values were reported for prevalence in a same population (e.g. using different scores), the highest value was selected for the general reporting of prevalence.

### 2.3.2 Scores

The proportion of use of the 3 scores (LEI, MASES and SPARCC) was collected. (10,11,13) Studies reporting several scores were counted several times.

### 2.3.3 Localization

The three most common sites affected by enthesitis were collected in each study (if available).

### 2.3.4 Consequences

Data collected were disease activity scores: Disease Activity Score DAS28 as it was the most used in the studies, C-reactive protein (CRP), other associated manifestations: dactylitis, nail psoriasis, swollen and tender joint count, Psoriasis Area Severity Index (PASI) score, treatment consumption (Disease-modifying antirheumatic drugs (DMARDs) and analgesics), pain, fatigue, quality of life assessments: EuroQoL (EQ5D), PsA Impact of Disease (PSAID), Health Assessment Questionnaire (HAQ). (25–29)

## 2.4 Statistical analysis

Patient characteristics and consequences of enthesitis were pooled using naïve pooling through weighted means. In cases where information was scarce, we opted for a straightforward presentation of the data without averaging.

Univariate random-effects meta-analysis was performed to calculate pooled percentages and pooled means in the overall population, including the prevalence of enthesitis and the number of enthesitis involved, using the “metafor” package from R software version 4.04.

Sensitivity analyses were performed (a) according to the type of study (i.e. observational studies or RCTs), (b) according to the year of publication, binarized as before or after 2019, and (c) according to the score used. To compare specifically the scores, only studies which reported several of the scores were used.

Heterogeneity was assessed through the I².

## 2.5 Role of funding source

This study did not receive any specific funding. The authors had full access to all data in the study and had final responsibility for the decision to submit for publication.

# 3 Results

## 3.1 Study selection and characteristics

In total, 852 publications were reviewed; 366 were analyzed in full-text and 212 were included in the analysis (<u>Figure 1</u>). Half of the studies were published after 2020; 164 (77.4%) were observational studies and 48 (22.6%) were RCTs; 66 (34.2%) were monocentric studies (<u>supplementary figure 1</u>).

Overall, 84,262 PsA patients were analyzed: the weighted mean age and disease duration were 50.2 (SD 3.1) years and 7.7 (SD 8.4) years respectively; 52.6% were women and the mean body mass index was 29.2 (5.4) kg/m2; 86.5% of patients were classified as PsA using the CASPAR criteria.(4) The population of patients with enthesitis appeared globally similar. (<u>Table 1</u>).

## 3.2 Prevalence of enthesitis

The pooled prevalence of enthesitis was 41.6% [95% confidence interval, 37.4-45.8]; heterogeneity was high (I² 100%) (<u>Table 2</u>). The prevalence was higher in RCTs (pooled
prevalence 67.2% [62.0-72.6]) than in observational studies (27.8% [24.5-31.2], p<0.001). There did not appear to be a link with the score used, nor a change in prevalence in recent studies (Figure 2).

### 3.3 Enthesitis scores

The most frequently used score was the LEI, used in 100/157 studies citing a score (63.7%), whereas the MASES was used in 52 studies (33.1%), and the SPARCC in 46 studies (29.3%). In recent studies, published after 2019, the LEI was most used (73.2% versus 50.0% before 2019, p<0.01) (supplementary table 1).

### 3.4 Number of enthesitis

When analyzing all the studies, the number of enthesitis per patient varied according to the score (Table 3), and was lower using the LEI (pooled mean, 1.39 [1.07-1.71]) than using the other scores (pooled mean 1.55 [0.77-2.34] with the MASES and 3.97 [2.76-5.17] with the SPARCC). The number of the pooled mean of the number of enthesitis according to the LEI also varied according to the type of study; it was higher in RCTs (pooled mean 2.12 [1.59-2.66]) than in observational studies (0.87 [0.50-1.24]).

These values were studies in 14 studies (i.e., 6576 patients) comparing the LEI and SPARCC scores, mostly RCTs (N=9), multicentric studies (N=12), were mainly published after 2020 (N=11). In these studies, the weighted mean age was 49.2 years, and the disease duration was 8.0 (SD 3.7) years; 49.9% were women. The prevalence and the pooled number of entheses involved per patient varied according to the score used, between 55.1% [39.7 - 70.84] and 1.61 [1.42-1.81] for the LEI, and 57.8% [43.9 - 71.8] and 5.67 [5.28-6.06] for the SPARCC respectively.

### 3.5 Localizations

The most common sites for enthesitis were reported in 31 studies (i.e. 16,971 patients), and were the Achilles tendon (part of the top 3 localizations in 64.5% studies), lateral epicondyle of the elbow (41.9%), plantar fascia (25.8%) and quadricipital tendon (22.6%). According to the score, the most frequently observed locations were: with the LEI in 6 studies lateral epicondyle of the elbow, Achilles tendon and medial condyle of the femur; for the MASES in 4 studies, chondrocostal, Achilles tendon and 5th lumbar spinous process; and for the SPARCC, in 9 studies, the lateral epicondyle of the elbow, the Achilles tendon and the plantar fascia.

### 3.6 Associated manifestations and consequences of enthesitis

Patients with enthesitis had higher disease activity than patients without enthesitis according to DAS28 (mean, 4.5 (1.1) versus 3.7 (1.1) reported in 8 studies); higher swollen and tender joint count (19 studies), and more frequent dactylitis (28% with enthesitis, 24% without) (Table 4). The occurrence of nail psoriasis and a higher PASI were reported in patients with enthesitis: 50% and 39.7% respectively for nail psoriasis, and 6.5 (7.4) and 5.4 (6.6) for PASI.

We also observed a higher proportion of fibromyalgia in patient with enthesitis than without (13.2% vs 3.8% in 3 studies, i.e. 2386 patients).

In 20 articles (i.e. 25,244 patients), the patient-reported impact of enthesitis was studied: patients with vs without enthesitis had higher pain, fatigue, depression, analgesic use and lower quality of life (Table 4 and supplementary table 2).

Very few articles (3 studies i.e. 6727 patients) mentioned the impact on work; enthesitis seemed to be associated with more sick leave, part-time therapy and worked time missed (supplementary table 2).

## 4 Discussion

This study is one of the rare studies focusing on enthesitis in PsA and brings to light important findings regarding this frequent feature of PsA. Enthesitis was a frequent
manifestation in PsA, with a pooled prevalence of 41.6%. Enthesitis was more prevalent in trials than in observational studies, reflecting recruitment patterns. The clinical assessment of enthesitis remains challenging, with heterogeneity in the scores used influencing the results. The most used score, particularly in recent studies, was the LEI which also led to a similar prevalence of enthesitis but the lowest number of entheses involved. The Achilles tendon was confirmed as the most frequent localization of enthesitis. Patients with enthesitis appeared to have more active disease; links with patients' quality of life should be further explored.

This study has strengths and weaknesses. The literature review was only performed in PubMed; however we were able to analyze 212 articles, leading to a high number of patients, which can be considered representative. The heterogeneity of the data was taken into account through random effects meta-analyses. General data about population (age, ethnicity, duration of PsA...) were not collected in patient without enthesitis, however, data of interest in this study were collected in the two groups. Localizations of enthesitis were analyzed as proportion of presence in the top three localizations of studies, and 181 studies did not report the localization. However, localization results are in agreement with previous studies, reinforcing the robustness of the present analyses. The association between enthesitis and other damage in PsA should be interpreted with caution since this potential association was assessed only through descriptive statistics, and we did not perform meta-regressions due to the low number of studies providing this information.

Prevalence of enthesitis was 41.6%; this is higher than a meta-analysis published in 2020, which found a prevalence of 30%.(2,7,20) Of note, half of the papers analyzed here were published after 2020, indicating a need for a new meta-analysis. The prevalence found here could be higher because recent studies report a higher prevalence, though this was not evidenced clearly in the present meta-analysis (Figure 2). The prevalence may be higher in the present meta-analysis because we used the highest prevalence in each study (when several prevalence rates were reported according to the different scores); and because we included many RCTs where the presence of enthesitis is very frequent. It is now well-demonstrated that patients in clinical trials tend to have more active disease than in clinical practice, and the present results confirm this finding for enthesitis. The prevalence of patients with enthesitis in this study was calculated in two ways. First, without considering the score and pooling all the studies in the same analysis. This approach could be criticized due to the different numbers and locations of entheses included in each index, but it provides an overall view of the PsA population.(30) Second, we stratified the analysis by the score used, and despite the different entheses evaluated, we found that the differences across indices were slight.

The present meta-analysis found that the most frequently used score was the LEI.(6) This was already the case in a previous study from 2018, where the LEI was the most used score followed by MASES and SPARCC.(2) The LEI only examines 6 peripheral enthesitis, so our hypothesis was that it could underestimate the number of enthesitis per patient. That is what we found when we compared studies using several scores. More sites are evaluated with the SPARCC, which gives a higher frequency in RCTs, and a higher number of entheses involved in all studies, compared to the LEI in particular. However, the LEI is easy to use, concerns the most frequent sites touched (though not plantar fascia), and shows good correlation with disease activity.(26)

Values found with LEI and MASES correspond to a previous study by Yang et al. which found a majority of patients with one or two sites affected.(8) The number of enthesitis per patient was higher in randomized trials, which may reflect a selection bias, and/or a more systematic assessment of entheses in the context of trials.

The Achilles tendon was the most frequent localisation of enthesitis. This confirms previous findings (14,15), although it is important to consider that the higher prevalence of Achilles tendon involvement may be explained by the fact that it is the only common site for the three
indices. We also found that enthesitis often affects the lateral epicondyle of the elbow and plantar fascia, as previously indicated.(8,12,15) Indeed, the SPARCC is the only score examining the plantar fascia; the LEI does not assess this important localization. However, plantar fascia pain is common and may be unrelated to inflammation.(20)

In this study, enthesitis was associated with higher disease activity. This finding goes in the direction of the concept of psoriatic disease, where inflammation touches both the entheses, the joints and the skin.(31)

Fibromyalgia was often reported in patient with enthesitis, in agreement with previous studies.(19,20) This may pose the question of either diagnostic difficulties since enthes seal pain may be mixed up with widespread pain; or the question of coexistence of active enthesitis and fibromyalgia.

Pain and functional scores seemed to be more impacted in patient with enthesitis, with higher analgesic use and more impact on work; however these data were rarely reported; other studies are necessary.(3)

To conclude, enthesitis was found to be extremely frequent in the present meta-analysis. Studies should focus on the efficacy of treatment option on enthesitis and a better understanding of links with patients' quality of life.

## Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

## Disclosures of interest

**Caroline Pignon, Noémie Bibas:** The authors declare that they have no competing interest.

**Clementina Lopez-Medina:** has received grants or contracts from AbbVie, Lilly, Novartis, UCB, and Janssen; consulting fees from Lilly, AbbVie, Novartis and UCB; honoraria for lectures from AbbVie, Janssen, Lilly, MSD, Novartis and UCB; has received support for attending meetings and/or travel from MSD, Novartis and UCB.

**Bruno Fautrel:** has received research grants from AbbVie, Lilly, MSD and Pfizer, and consultancy fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Chugai, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, OWKIN, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Viatris.

**Laure Gossec:** has received grants or contracts from AbbVie, Biogen, Lilly, Novartis, UCB, consulting fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer, UCB, honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, has received support for attending meetings and/or travel from MSD, Novartis, Pfizer.

## References

1. McInnes IB, Puig L, Gottlieb AB, Ritchlin CT, Song M, You Y, et al. Association Between Enthesitis and Health-related Quality of Life in Psoriatic Arthritis in Biologic-naive Patients from 2 Phase III Ustekinumab Trials. J Rheumatol. nov 2019;46(11):1458-61.

2. Kaeley GS, Eder L, Aydin SZ, Gutierrez M, Bakewell C. Enthesitis: A hallmark of psoriatic arthritis. Semin Arthritis Rheum. août 2018;48(1):35-43.

3. Mease PJ, Karki C, Palmer JB, Etzel CJ, Kavanaugh A, Ritchlin CT, et al. Clinical Characteristics, Disease Activity, and Patient-Reported Outcomes in Psoriatic Arthritis Patients With Dactylitis or Enthesitis: Results From the Corrona Psoriatic Arthritis/Spondyloarthritis Registry. Arthritis Care Res. nov 2017;69(11):1692-9.

4. Taylor W, Gladman D, Helliwell P, marchesoni antonio, Mease, Philip, Herman miela. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. [cité 18 mars 2024]; Disponible sur: https://onlinelibrary.wiley.com/doi/10.1002/art.21972

5. Orbai AM, Weitz J, Siegel EL, Siebert S, Savage LJ, Aydin SZ, et al. Systematic Review of Treatment Effectiveness and Outcome Measures for Enthesitis in Psoriatic
Arthritis. J Rheumatol. 1 nov 2014;41(11):2290-4.

6. Mathew AJ, Glintborg B, Krogh NS, Hetland ML, Østergaard M. Enthesitis in patients with psoriatic arthritis and axial spondyloarthritis - data from the Danish nationwide DANBIO registry. Semin Arthritis Rheum. févr 2022;52:151948.

7. Pittam B, Gupta S, Harrison NL, Robertson S, Hughes DM, Zhao SS. Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis. Rheumatol Oxf Engl. 1 sept 2020;59(9):2199-206.

8. Yang F, Lu C, Liu H, Dou L, Wang Y, Li H, et al. Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR). Chin Med J (Engl). 20 avr 2023;136(8):951-8.

9. Lo Gullo A, Becciolini A, Parisi S, Del Medico P, Farina A, Visalli E, et al. Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study. J Clin Med. 7 juin 2023;12(12):3892.

10. Gladman DD, Cook RJ, Schentag C, Feletar M, Inman RI, Hitchon C, et al. The clinical assessment of patients with psoriatic arthritis: results of a reliability study of the spondyloarthritis research consortium of Canada. J Rheumatol. 1 juin 2004;31(6):1126-31.

11. Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 15 mai 2008;59(5):686-91.

12. Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. nov 2015;41(4):545-68.

13. Heuft-Dorenbosch L, Spoorenberg A, Tubergen A van, Landewé R, Tempel H van der, Mielants H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 1 févr 2003;62(2):127-32.

14. Vandendorpe AS, de Vlam K, Lories R. Evolution of psoriatic arthritis study patient population characteristics in the era of biological treatments. RMD Open. 2019;5(1):e000779.

15. Polachek A, Li S, Chandran V, Gladman DD. Clinical Enthesitis in a Prospective Longitudinal Psoriatic Arthritis Cohort: Incidence, Prevalence, Characteristics, and Outcome. Arthritis Care Res. nov 2017;69(11):1685-91.

16. Sunar I, Ataman S, Nas K, Kilic E, Sargin B, Kasman SA, et al. Enthesitis and its relationship with disease activity, functional status, and quality of life in psoriatic arthritis: a multi-center study. Rheumatol Int. févr 2020;40(2):283-94.

17. Carneiro S, Bortoluzzo A, Gonçalves C, Silva JAB da, Ximenes AC, Bértolo M, et al. Effect of Enthesitis on 1505 Brazilian Patients with Spondyloarthritis. J Rheumatol. 1 oct 2013;40(10):1719-25.

18. Walsh JA, Ogdie A, Michaud K, Peterson S, Holdsworth EA, Karyekar CS, et al. Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe. Joint Bone Spine. mai 2023;90(3):105534.

19. Moltó A, Etcheto A, Gossec L, Boudersa N, Claudepierre P, Roux N, et al. Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers' effectiveness in axial spondyloarthritis: results of a prospective, multicentre study. Ann Rheum Dis. avr 2018;77(4):533-40.

20. Fitzgerald GE, Maguire S, Lopez-Medina C, Dougados M, O'Shea FD, Haroon N. Tender to touch-Prevalence and impact of concomitant fibromyalgia and enthesitis in spondyloarthritis: An ancillary analysis of the ASAS PerSpA study. Joint Bone Spine. 1 nov 2022;89(6):105420.

21. Chapter 10: Analysing data and undertaking meta-analyses [Internet]. [cité 29 mars 2024]. Disponible sur: https://training.cochrane.org/handbook/current/chapter-10

22. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. [cité 29 mars 2024]. Disponible sur: https://training.cochrane.org/handbook

23. PubMed [Internet]. [cité 8 avr 2024]. PubMed. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/

24. Rayyan – Intelligent Systematic Review - Rayyan [Internet]. [cité 8 avr 2024]. Disponible sur: https://www.rayyan.ai/
25. van Riel PL, Fransen J. DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis. Arthritis Res Ther. 22 août 2005;7(5):189.

26. Mease, Philip PJ. Measures of psoriatic arthritis: Tender and Swollen Joint Assessment, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified Nail Psoriasis Severity Index (mNAPSI), Mander/Newcastle Enthesitis Index (MEI), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). [cité 22 mars 2024]; Disponible sur: https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.20577

27. Hurst NP, Kind P, Ruta D, Hunter M, Stubbings A. Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol. mai 1997;36(5):551-9.

28. Gossec L, Wit M de, Kiltz U, Braun J, Kalyoncu U, Scrivo R, et al. A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis. 1 juin 2014;73(6):1012-9.

29. WOLFE F, PINCUS T, FRIES J, GREENWOOD M, DOYLE D. Usefulness of the HAQ in the clinic. Ann Rheum Dis. août 2001;60(8):811.

30. Granados REM, Ladehesa-Pineda ML, Puche-Larrubia MÁ, Escudero-Contreras A, Dougados M, Collantes-Estevez E, et al. Enthesitis indices identify different patients with this characteristic in axial and peripheral spondyloarthritis and also in psoriatic arthritis: ASAS-PerSpA data. Arthritis Res Ther. 2023;25:99.

31. Tan AL, McGonagle D. Psoriatic arthritis: correlation between imaging and pathology. Joint Bone Spine. mai 2010;77(3):206-11.
<figure><img src="image_3.png" /><figcaption>**Figure 1.** Flowchart of study selection, of articles reporting clinical enthesitis in PsA published 2010-2023.</figcaption></figure>

Footnote – ‘Not specifically PsA’ corresponds to studies of spondyloarthritis which did not give results separately for PsA.
<table><caption>**Table 1.** Characteristics of PsA patients in 212 studies reporting information on enthesitis</caption><thead><tr><th>Variables</th><th>All PsA patients<br>N=84262</th><th>PsA patients with enthesitis<br>N=28475</th></tr></thead><tbody><tr><td>Age, years</td><td>50.2 (3.1) [70,616]</td><td>49.0 (12.6) [6564]</td></tr><tr><td>Female sex, %</td><td>52.6 [79,699]</td><td>53.8 [6357]</td></tr><tr><td>Caucasian ethnicity, %</td><td>89.8 [31,421]</td><td>93.3 [1680]</td></tr><tr><td>PsA duration, years</td><td>7.7 (8.4) [60,153]</td><td>8.0 (6.2) [6212]</td></tr><tr><td>csDMARD therapy, %</td><td>50.0 [44,126]</td><td>48.6 [4813]</td></tr><tr><td>b/tsDMARD therapy, %</td><td>43.2 [33,934]</td><td>35.6 [2454]</td></tr><tr><td>Body mass index, kg/m<sup>2</sup></td><td>29.2 (5.4) [55,558]</td><td>29.4 (9.1) [6213]</td></tr><tr><td>Obesity, %</td><td>44.1 [12,622]</td><td>45.9 [1965]</td></tr><tr><td>Fibromyalgia or widespread<br>pain syndrome, %</td><td>13.9 [14,306]</td><td>13.2 [705]</td></tr></tbody></table>

Footnote - Unless indicated otherwise, data are presented as weighted mean (SD) [N patients analysed]

csDMARD: conventional disease-modifying antirheumatic drugs

b/tsDMARD: synthetic or biologic disease-modifying antirheumatic drugs
<table><caption>**Table 2.** Frequency of enthesitis in patients with PsA overall and according to the type of study and the score used.</caption><thead><tr><th></th><th>Number studies</th><th>of</th><th>Number patients</th><th>of</th><th>Pooled percentage (95%CI)</th><th>Heterogeneity (I<sup>2</sup>) and p-value of I<sup>2</sup></th></tr></thead><tbody><tr><td colspan="7"><strong>Overall population</strong></td></tr><tr><td>Patients with enthesitis</td><td>161</td><td></td><td>77,045</td><td></td><td>41.6 (37.4-45.8)</td><td>100% (&lt;0.001)</td></tr><tr><td>RCT</td><td>41 (25.5% of 161)</td><td></td><td>23,626</td><td></td><td>67.2 (62.0-72.6)</td><td>100% (&lt;0.001)</td></tr><tr><td>Observational</td><td>120 (74.5%)</td><td></td><td>53,419</td><td></td><td>27.8 (24.5-31.2)</td><td>99.1% (&lt;0.001)</td></tr><tr><td colspan="7"><strong>LEI</strong></td></tr><tr><td>Patients with enthesitis</td><td>64</td><td></td><td>24,126</td><td></td><td>50.3 (43.6-56.9)</td><td>100% (&lt;0.001)</td></tr><tr><td>RCT</td><td>28 (43.8% of 64)</td><td></td><td>15,705</td><td></td><td>64.3 (56.8-71.7)</td><td>100% (&lt;0.001)</td></tr><tr><td>Observational</td><td>36 (56.2%)</td><td></td><td>8421</td><td></td><td>33.4 (25.8-41.0)</td><td>95.1% (&lt;0.001)</td></tr><tr><td colspan="7"><strong>MASES</strong></td></tr><tr><td>Patients with enthesitis</td><td>27</td><td></td><td>10,373</td><td></td><td>46.7 (40.5-62.8)</td><td>100% (&lt;0.001)</td></tr><tr><td>RCT</td><td>7 (26.0% of 27)</td><td></td><td>4496</td><td></td><td>71.0 (66.2-75.9)</td><td>74.3% (&lt;0.001)</td></tr><tr><td>Observational</td><td>20 (74.0%)</td><td></td><td>5877</td><td></td><td>33.6 (23.9-43.3)</td><td>94.9% (&lt;0.001)</td></tr><tr><td colspan="7"><strong>SPARCC</strong></td></tr><tr><td>Patients with enthesitis</td><td>26</td><td></td><td>25,865</td><td></td><td>49.3 (37.3-61.4)</td><td>100% (&lt;0.001)</td></tr><tr><td>RCT</td><td>8 (30.8% of 26)</td><td></td><td>5118</td><td></td><td>72.3 (68.1-76.5)</td><td>73.8% (0.002)</td></tr><tr><td>Observational</td><td>18 (69.2%)</td><td></td><td>20747</td><td></td><td>25.4 (17.1-33.8)</td><td>99.5% (&lt;0.001)</td></tr></tbody></table>

RCT: randomized controlled trials; OBS: observational studies
**Figure 2.** Prevalence of enthesitis in patients with PsA: forest plot with pooled prevalence by year of publication, for 44 studies with more than 500 patients.

Proportion of patients with enthesitis

<figure><img src="image_4.png" /></figure>

S

Footnote – the systematic literature review included 212 studies; this graph shows the prevalence of enthesitis only in the 44 studies with more than 500 patients. For these studies, the pooled prevalence was 44.8% (95% CI, 37.7-52.0).
<table><caption>**Table 3.** Number of enthesitis in patients with enthesitis according to the score and the type of study.</caption><thead><tr><th></th><th>Number of studies</th><th>Number of patients</th><th>Pooled (95%CI)</th><th>mean</th><th>Heterogeneity (I²) and p-value of I²</th></tr></thead><tbody><tr><td colspan="6"><strong>LEI</strong></td></tr><tr><td>Number of enthesitis</td><td>47</td><td>7964</td><td>1.39 (1.07-1.71)</td><td>14.9% (0.771)</td><td></td></tr><tr><td>RCT</td><td>20 (42.6% of 47)</td><td>6342</td><td>2.12 (1.59-2.66)</td><td>12.6% (0.952)</td><td></td></tr><tr><td>Observational</td><td>27 (57.4%)</td><td>1622</td><td>0.87 (0.50-1.24)</td><td>0.0% (0.971)</td><td></td></tr><tr><td colspan="6"><strong>MASES</strong></td></tr><tr><td>Number of enthesitis</td><td>26</td><td>4379</td><td>1.55 (0.77-2.34)</td><td>0.0% (0.999)</td><td></td></tr><tr><td>RCT</td><td>7 (26.9% of 26)</td><td>2710</td><td>2.93 (0.69-4.97)</td><td>0.0% (0.669)</td><td></td></tr><tr><td>Observational</td><td>19 (73.1%)</td><td>1169</td><td>1.36 (0.52-2.20)</td><td>0.0% (1.000)</td><td></td></tr><tr><td colspan="6"><strong>SPARCC</strong></td></tr><tr><td>Number of enthesitis</td><td>21</td><td>5520</td><td>3.97 (2.76-5.17)</td><td>25.9% (0.388)</td><td></td></tr><tr><td>RCT</td><td>7 (33.3% of 21)</td><td>2018</td><td>5.69 (5.30-6.08)</td><td>0.0% (0.998)</td><td></td></tr><tr><td>Observational</td><td>15 (71.4%)</td><td>3502</td><td>2.93 (1.59-4.27)</td><td>0.0% (0.973)</td><td></td></tr></tbody></table>

Footnote - RCT: randomized control trials.

OBS:

observational

studies
<table><caption>**Table 4.** Characteristics and consequences of PsA in patient with versus without enthesitis</caption><thead><tr><th>Variables</th><th>Enthesitis</th><th>Without enthesitis</th></tr></thead><tbody><tr><td>SJC</td><td>7.2 (6.3) [5456]</td><td>5.5 (4.9) [14246]</td></tr><tr><td>TJC</td><td>15.2 (12.1) [5456]</td><td>8.6 (7.2) [14246]</td></tr><tr><td>Dactylitis, %</td><td>28.2 [4543]</td><td>24.0 [7996]</td></tr><tr><td>Nail psoriasis, %</td><td>50.0 [2397]</td><td>39.7 [6196]</td></tr><tr><td>DAS 28</td><td>4.5 (1.1) [3340]</td><td>3.7 (1.1) [6367]</td></tr><tr><td>CRP</td><td>3.7 (6.1) [3388]</td><td>4.9 (8.2) [8299]</td></tr><tr><td>PASI</td><td>6.5 (7.4) [3625]</td><td>5.4 (6.6) [2292]</td></tr><tr><td>HLA B27, %</td><td>18.9 [1747]</td><td>19.0 [7771]</td></tr><tr><td>IBD, %</td><td>3.4 [513]</td><td>3.3 [3675]</td></tr><tr><td>Fibromyalgia</td><td>13.2 [705]</td><td>3.8 [1681]</td></tr><tr><td>csDMARD, %</td><td>48.6 [4813]</td><td>45.3 [4918]</td></tr><tr><td>b/tsDMARD, %</td><td>35.6 [2454]</td><td>23.2 [3555]</td></tr><tr><td>Pain scale NRS (0-10)</td><td>5.2 (2.3) [1285]</td><td>3.9 (2.2) [8949]</td></tr><tr><td>Pain scale VAS (0-100)</td><td>55.4 (23.1) [2253]</td><td>56.0 (22.7) [5078]</td></tr><tr><td>HAQ</td><td>1.1 (0.7) [6118]</td><td>0.9 (0.6) [15,642]</td></tr><tr><td>EQ5D</td><td>0.7 (0.2) [1347]</td><td>0.8 (0.2) [6655]</td></tr><tr><td>PS-AID 12</td><td>3.9 (2.9) [514]</td><td>2.4 (2.0) [5043]</td></tr></tbody></table>

Data are presented as weighted mean (SD) or % [number of patients contributing to the analysis].

SJC: swollen joint count; TJC: Tender joint count; DAS 28: Disease activity score; CRP: C-reactive protein; PASI: Psoriasis Area Severity Index; IBD: inflammatory bowel disease; csDMARD: conventional disease-modifying antirheumatic drugs; b/ts: biologic and synthetic DMARD; NRS: Numerical Rating Scale; VAS: visual analogue scale; HAQ: Health Assessment Questionnaire ; EQ5D: EuroQoL; PSAID: PsA Impact of Disease.
<table><caption>**Supplementary table 1.** Use of enthesitis scores according to the publication date</caption><thead><tr><th></th><th>2010 to 2018<br>N = 58</th><th>2019 to 2023<br>N = 97</th><th>p-value</th></tr></thead><tbody><tr><td>LEI</td><td>29 (50.0%)</td><td>71 (73.2%)</td><td>0.003</td></tr><tr><td>MASES</td><td>26 (44.8%)</td><td>26 (26.8%)</td><td>0.021</td></tr><tr><td>SPARCC</td><td>14 (24.1%)</td><td>32 (33.0%)</td><td>0.243</td></tr></tbody></table>
<table><caption>**Supplementary table 2.** Consequences of the presence of enthesitis in PsA</caption><thead><tr><th>Variable</th><th></th><th>Enthesitis</th><th>Without enthesitis</th></tr></thead><tbody><tr><td rowspan="3">Consumption of treatment</td><td>NSAID</td><td>44.4 [205]</td><td>22.9 [2952]</td></tr><tr><td></td><td>46.1 [308]</td><td>36.8 [723]</td></tr><tr><td>Opioid</td><td>8.3 [205]</td><td>1.9 [2952]</td></tr><tr><td></td><td>Non-opioid antalgic</td><td>10.7 [205]</td><td>5.4 [2952]</td></tr><tr><td>Satisfaction</td><td></td><td>57.6 [205]</td><td>84.4 [2952]</td></tr><tr><td>Depression</td><td></td><td>19.4 [391]</td><td>12.3 [1612]</td></tr><tr><td rowspan="4">Work consequences</td><td>Sick leave</td><td>7.5 [205]</td><td>2.1 [2952]</td></tr><tr><td>Half-time work</td><td>52.8 [205]</td><td>41.9 [2952]</td></tr><tr><td></td><td>8.3 [391]</td><td>8.4 [1612]</td></tr><tr><td>Missed work time</td><td>15.6 [391]</td><td>14.3 [1612]</td></tr><tr><td></td><td></td><td>5.3 [420]</td><td>3.8 [1147]</td></tr></tbody></table>

Values are reported as percentage of patients concerned [number of patients with or without enthesitis in the study].

A line corresponds to one study.

NSAID: non-steroidal anti-inflammatory drug
<figure><img src="image_5.png" /><figcaption>**Supplementary Figure 1.** Number of studies according to the year of publication</figcaption></figure>

Footnote – the size of the bubble represents total number of patients included in a year.
Median date of publication was 2020 (2009-2023).