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Abstract
Background Within the spectrum of spondyloarthritides, axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) present with overlapping features. Axial involvement in PsA (axial PsA) is treated according to recommendations for axSpA, as specific studies in axial PsA are scarce. We compared characteristics of patients with axSpA (particularly of patients with axSpA and concomitant psoriasis (pso)) with those of patients with axial PsA.
Methods Patients with axSpA and PsA in the Swiss Clinical Quality Management (SCQM) registry were included if information on pso and axial involvement was available. Patients with AxSpA were stratified by axSpA with and without pso (axSpA±pso) and patients with PsA were stratified to axial PsA or strictly peripheral PsA.
Results Previous or current psoriasis was observed in 479/4489 patients with axSpA (10.7%). Of 2631 patients with PsA, 1153 (43.8%) presented with axial involvement (opinion of the treating rheumatologist). Compared with patients with axSpA+pso, patients with axial PsA were older at symptom onset and at inclusion in SCQM, were less frequently HLA-B27 positive, had back pain less frequently and a higher prevalence of dactylitis and peripheral arthritis. A positive family history of pso or PsA was more frequent in axial PsA, while a positive family history of axSpA was more frequent in patients with axSpA+pso. Disease activity, function and mobility were comparable in axSpA+pso versus axial PsA.
Conclusion Patients with axial PsA differ from patients with axSpA+pso in important demographic and clinical characteristics, and genetically, but present with a comparable disease burden. Treatment studies specifically dedicated to axial PsA seem warranted.
- Spondylitis, Ankylosing
- Arthritis, Psoriatic
- Epidemiology
Data availability statement
Data may be obtained from a third party and are not publicly available. Restrictions apply to the availability of these data. Data are owned by a third party, the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) foundation. Data may be obtained after approval and permission from the license holder (SCQM). Contact information for data requests: scqm@hin.ch.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
There is a substantial overlap in manifestations between axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) as part of the spectrum of the spondyloarthritides.
Patients with PsA and axial involvement (axial PsA) are treated according to the recommendations for axSpA.
WHAT THIS STUDY ADDS
Patients with axSpA and concomitant psoriasis differ substantially from those with axial PsA regarding genetics, demographics and clinical phenotype.
The differences persisted in HLA-B27 positive individuals.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The findings suggest that axSpA and axial PsA might be distinct entities.
Treatment studies specifically dedicated to axial PsA need to be conducted as soon as a consensus is found on the definition of axial involvement in PsA.
Introduction
The spectrum of spondyloarthritides (SpA) encompasses a group of overlapping inflammatory rheumatic diseases: ankylosing spondylitis (extended to axial spondyloarthritis (axSpA) to include earlier and milder disease forms), psoriatic arthritis (PsA), enteropathic SpA and reactive arthritis.1 These disorders feature common musculoskeletal manifestations to differing degrees and with different emphases (inflammatory axial involvement at the level of the sacroiliac joints and the spine, proximal or peripheral arthritis, enthesitis and dactylitis). The diseases also share some extramusculoskeletal manifestations (EMM): uveitis, psoriasis and inflammatory bowel disease (IBD). The overlapping nature of the diseases within the SpA spectrum led to the development of classification criteria by the Assessment of SpondyloArthritis international Society (ASAS), which mainly differentiates between predominantly axial and predominantly peripheral manifestations.2 3 A patient with inflammatory axial involvement and psoriasis can be classified as having axSpA through the ASAS classification criteria2 or having PsA according to the ClASsification for Psoriatic ARthritis (CASPAR) criteria.4 The terminology used to describe axial involvement in PsA has been diverse: psoriatic spondylitis, psoriatic SpA and axial PsA, among others.5–7 Moreover, there is no consensus on a definition of axial involvement in PsA.8 Whether axSpA and axial PsA represent the same or different disorders remains controversial.9 The suggestion that, in contrast to axSpA, axial PsA might respond to treatment with interleukin-23 inhibitors (IL-23i) has brought the issue into the spotlight.10 11 Awaiting a consensus on the definition of axial PsA,8 we compared the phenotype of patients with axial PsA versus axSpA in two different cohorts within a large national observational registry of patients with inflammatory rheumatic diseases (axSpA and PsA cohorts, respectively).
Methods
Study population
The Swiss Clinical Quality Management (SCQM) Foundation initiated an ongoing cohort of patients diagnosed as having axSpA in 2005 and a parallel cohort of patients diagnosed as having PsA in 2006.12 13 The primary aim of the registry is to provide direct feedback to the treating rheumatologist in private practice or a non-academic or academic institution on validated disease measures and assist with treating the respective disease to target. Criteria for inclusion in SCQM are a clinical diagnosis by the rheumatologist for the respective disease, informed consent for participation and ability to fill out questionnaires in one of the official Swiss languages (German, French or Italian). The individual items of the ASAS classification criteria are collected for the axSpA cohort and the items of the CASPAR classification criteria are collected for the PsA cohort.2 4 The study represents a cross-sectional comparison of the two ongoing cohorts at the time-point of inclusion of each patient into the SCQM registry. Prior to 2006, the rheumatologists had no choice to include patients with inflammatory axial disease and concomitant psoriasis in either the axSpA cohort or the PsA cohort. Therefore, inclusions were only considered after initiation of the PsA cohort in January 2006 and up to the end of February 2023. Moreover, we excluded patients with missing data on the presence of psoriasis or axial involvement from the primary analyses. These patients were added to the comparison of the two cohorts in a sensitivity analysis. Assessment of patients with axSpA was performed according to the recommendations of ASAS.14 Data on the Bath Ankylosing Spondylitis Disease Activity, Functional and Mobility Indices (BASDAI, BASFI and BASMI, respectively) as well as the Patient Assessment of Global Disease Activity were available for two-thirds of the axSpA population but only in a minority of patients with PsA, as this information was only collected in the PsA cohort from 2021. Information on the Physician Global Assessment of Disease Activity, Short-Form 12 questions (SF-12) and the European Quality of Life with 5 dimensions questionnaire (EQ-5D) was collected since cohort initiation and was available in a comparable proportion of patients in both cohorts, as was information on C reactive protein (CRP) levels and human leucocyte antigen B27 (HLA-B27). Peripheral disease was assessed with regard to the previous or current presence of peripheral arthritis, previous or current presence of enthesitis (Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and ever dactylitis. While the 44-joint count was used in axSpA and the 66/68-joint count in PsA, the former was used for comparative analyses of both cohorts. The MASES score used was modified to include the proximal insertion of the plantar fasciae bilaterally. EMMs included the presence of ever uveitis, ever IBD and ever psoriasis, with information on current psoriatic involvement of skin and nails available only in the PsA cohort. Missing characteristics at the time-point of inclusion were mapped from visits closest to inclusion if within a range of 100 days (only 10 days for disease activity variables). Family history and information on HLA-B27 status were mapped from any visit. Medication start and stop dates were available for all conventional-synthetic, targeted-synthetic or biological disease-modifying antirheumatic drugs (cs/ts/bDMARDs). Specific data were available for tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), interleukin-23 inhibitors (IL-23i), Janus kinase inhibitors (JAKi) and phosphodiesterase-4 inhibitors. Data on nonsteroidal anti-inflammatory drugs (NSAIDs) were collected as yes/no. Written informed consent was obtained from all patients prior to inclusion into SCQM.
Definition of axial involvement in the PsA cohort
Axial involvement was considered in the PsA cohort if the following question in the rheumatologist’s questionnaire was answered with yes: ‘Does your patient currently have or has he/she ever had axial involvement?’ Additional information on axial involvement was derived from the manifestations tab, where the treating rheumatologist can indicate the presence of sacroiliitis and spinal involvement separately as either clinically and/or radiographically and/or by MRI. The grade or the symmetry of sacroiliitis and the exact features of spinal involvement on X-rays (eg, typical syndesmophytes vs coarse non-marginal syndesmophytes) are not collected.15 When the respective imaging item is not reported, differentiation between ‘imaging negative’ or ‘imaging not performed’ is not possible. Data on back pain for at least 3 months and of IBP were collected independently of the question on axial involvement of SpA. However, the questionnaire did not include information regarding the localisation of back pain (cervical, thoracic or lumbar). Pelvis radiographs were collected in the axSpA cohort, but not in the PsA cohort. Central scoring of the sacroiliac joints according to the modified New York classification criteria performed at regular intervals as a service to the treating rheumatologist was, therefore, only available in the axSpA population in patients with radiographs sent to SCQM or uploaded to the online database.
Statistical analyses
R statistical software was used for the statistical analyses. Patient characteristics were compared using the Fisher’s exact test for categorical variables and the Kruskal test for continuous variables. All tests were two-sided with the significance level set at 0.05.
Results
Comparison of the two SCQM cohorts (axSpA vs PsA)
Patient disposition in the SCQM cohort is displayed in figure 1. From 8815 patients (5812 axSpA and 3003 PsA) recruited into SCQM, 604 patients with axSpA and 232 patients with PsA were excluded, as their inclusion visit predated the initiation of the PsA cohort. Comparison of baseline characteristics at the time-point of recruitment into SCQM of the remaining 5208 patients with axSpA and 2771 patients with PsA is shown in table 1. The proportion of women was higher and patients were older in PsA compared with axSpA. Axial symptoms, enthesitis, uveitis and IBD were more frequent in axSpA, while peripheral arthritis and dactylitis were more prevalent in PsA. Patient and physician global disease activity levels were higher in axSpA, paralleling a worse generic health status as assessed by the mental and the physical component summary scores of the SF-12 questionnaire, as well as a more impaired health-related quality of life. Regarding medication, a higher proportion of patients with axSpA were on treatment with NSAIDs and with TNFi, while more patients with PsA were treated with IL-17i, IL-23i and tsDMARDs. In light of the higher percentage of patients with a history of peripheral arthritis in the PsA cohort, more patients were on treatment with csDMARDs in this group, compared with patients with axSpA. Similar results were found for the comparison of the two cohorts when only patients with available information on the presence or history of psoriasis and of axial involvement were considered (N=4489 for axSpA and N=2631 for PsA; table 1). The proportion of patients fulfilling the respective classification criteria was 75% for axSpA (ASAS) and 87% for PsA (CASPAR).
Disposition of patients in the axSpA and PsA SCQM cohorts, particularly with regard to axial and psoriatic involvement. axSpA, axial spondyloarthritis; PsA, psoriatic arthritis; SCQM, Swiss Clinical Quality Management.
Characteristics of patients with axSpA and PsA at inclusion in SCQM
Comparison of patients with axSpA with and without psoriasis
The proportion of patients with a history of or current psoriasis in the axSpA cohort was 11%. Comparison of characteristics of patients with axSpA without psoriasis (N=4010) and patients with axSpA with psoriasis (axSpA+pso) are shown in detail in tables 2–5. While sex distribution was comparable between the two groups, HLA-B27 positivity was less prevalent in patients with psoriasis, leading to a slightly lower proportion of patients fulfilling the ASAS classification criteria in this group. Patients with AxSpA+pso were older and had longer symptom duration, despite a later onset of symptoms in comparison to patients without psoriasis (table 2). No differences between the groups could be observed for axial involvement and uveitis, while a higher proportion of patients with axSpA+pso had peripheral musculoskeletal manifestations (table 3). Disease activity was higher, and function as well as spinal mobility was more severely impaired in patients with axSpA+pso (table 4). More patients in the axSpA+pso group were already treated with csDMARDs at inclusion, reflecting the higher prevalence of peripheral arthritis in this group (table 5).
Demographic and defining characteristics of patients with axSpA (without and with psoriasis) and PsA (with and without axial involvement)
Musculoskeletal and extramusculoskeletal clinical manifestations in patients with axSpA (without and with psoriasis) and PsA (with and without axial involvement)
Disease activity, function and quality of life in patients with axSpA (without and with psoriasis) and PsA (with and without axial involvement)
Pharmacological treatment in patients with axSpA (without and with psoriasis) and PsA (with and without axial involvement)
Patients with AxSpA with psoriasis versus axial PsA
Comparison of the axSpA+pso group (N=479) versus the axial PsA group (N=1153) is also shown in tables 2–5. The axial PsA group in SCQM is characterised by an older age at first symptoms, older age at inclusion, shorter diagnostic delay and shorter symptom duration, as well as by a significantly lower prevalence of HLA-B27 positivity (22% vs 55.4% in axSpA+pso, p<0.001; table 2). Significant differences between the two populations were also observed for the family history of axSpA, PsA and psoriasis, respectively (table 2). Body mass index as well as the prevalence of obesity was higher in axSpA+pso than in axial PsA. The following differences regarding axial involvement were detected: the proportion of patients with back pain ≥3 months, with IBP, as well as with ever sacroiliitis was significantly lower in axial PsA (table 3). Differences were also identified regarding peripheral musculoskeletal involvement: 43% vs 18% ever dactylitis, 87% vs 58% ever peripheral arthritis, for axial PsA vs axSpA+pso, respectively (table 3). In contrast, we did not detect differences in enthesitis between the two groups. Regarding disease activity assessments, physician global disease activity and the height of CRP elevation were comparable between the two groups, as were the parameters developed for axSpA (BASDAI and ASDAS), the latter being, however, only available in a minority of patients with axial PsA (table 4). Differences in the pharmacological treatment of the two groups reflected the respective differences in musculoskeletal involvement, with NSAIDs being more frequently used in axSpA+pso, while csDMARDs and steroids being more frequently used in axial PsA (table 5).
To investigate whether the differences in phenotype between axSpA+pso and axial PsA might be due to the distinct prevalence of HLA-B27 positivity, we compared the two groups after stratification for HLA-B27 (table 6). In HLA-B27-positive patients, as well as in HLA-B27-negative patients, differences between axSpA+pso and axial PsA persisted and encompassed a later onset of symptoms, an older age, a less important axial and a more frequent peripheral involvement in axial PsA (table 6). Against an HLA-B27 background, a positive family history of psoriasis was found in only 17% of patients with axSpA+pso vs 32% of patients with axial PsA (p=0.003). A family history of axSpA was more often mentioned in axSpA+pso and a family history of PsA was more often found in axial PsA than vice versa (table 6).
Comparison of patients with axSpA and concomitant psoriasis vs axial PsA after stratification by HLA-B27 status
Axial versus peripheral PsA
Finally, we compared patients with axial versus strictly peripheral disease in the PsA cohort (N=1153 and N=1478, respectively, tables 2–5). Fulfilment of CASPAR classification criteria (88% vs 86%, p=0.15) and sex distribution (female sex: 51% vs 48%, p=0.20) were comparable between the two groups (table 2). Back pain of at least 3 months duration was found in 12% of patients with peripheral PsA, indicating that the rheumatologists had interpreted the back pain as not due to PsA in this group (table 3). Only a minority of patients in this group complained of IBP (2.6%). The majority of patients with peripheral PsA had a history of peripheral arthritis (96%) and 84% had current arthritis with a higher mean number of swollen joints compared with patients with axial PsA. Enthesitis was, however, less prevalent and the MASES lower in peripheral than in axial PsA (table 3).
Discussion
Our analysis of 4489 patients with axSpA and 1153 patients with axial PsA from a large national observational registry adds important data to earlier investigations to support the notion of two distinct entities.16–19 Differences in inclusion criteria between the studies should be highlighted. In an analysis from Bath featuring 400 cases axSpA and PsA, only patients with radiographic disease were included.16 Moreover, ankylosing spondylitis patients with psoriasis and patients with axial PsA were pooled together. Feld et al presented 1243 cases with axSpA and axial PsA identified by definite radiographic sacroiliitis from separate AS and PsA Clinics in Toronto.17 The study from Madrid, by Benavent et al, included 352 cases of patients with axSpA and axial PsA, encompassing both the non-radiographic and the radiographic spectrum, but initiating treatment with bDMARDs.18 Our analysis had a design comparable with the recent study from the German RABBIT-SpA registry of 1787 patients with axSpA and axial PsA.19 Patients were diagnosed as having either axSpA or PsA by their treating rheumatologist and were included in the respective cohorts based on clinical grounds and imaging. Both our study and the study by Regierer et al focused on patients with axSpA+pso versus patients with axial PsA.19 We have chosen the expert opinion of the treating rheumatologist based on all data available to define axial involvement in axial PsA, which was summarised by his/her confirmation that the patient with PsA had axial involvement. Additional validation of the definition came from information on sacroiliac joint or spinal involvement clinically or on imaging. The proportion of patients with PsA fulfilling the CASPAR classification criteria4 was comparable in axial versus peripheral PsA.
In contrast to patients with axSpA+pso, patients with axial PsA have a significantly later symptom onset, a lower prevalence of back pain and sacroiliitis and a significantly higher prevalence of peripheral arthritis and dactylitis, but not enthesitis. Regarding the EMM, uveitis and IBD were more frequently seen in axSpA+Pso than in axial PsA. In general, we confirm the differences between axial PsA and axSpA with concomitant psoriasis found in earlier studies.17 19 Some of the mentioned differences are known to be associated with the presence of HLA-B27 positivity,20 21 which was lower in axial PsA. However, HLA-B27 status did not fully explain the differences between patients with axSpA+pso and patients with axial PsA, as the amplitude of the differences remained after stratification for this genetic marker. However, HLA-B27 status might influence the radiographic phenotype in axial involvement of both axSpA and axial PsA, as demonstrated in a recent study.22 Indeed, HLA-B27 positive patients had—in contrast to HLA-B27 negative patients—more severe radiographic damage, more marginal syndesmophytes and more frequent symmetrical syndesmophytes in a recent analysis. As radiographs of the axial skeleton were not collected in the PsA cohort in SCQM, we could not address this issue.
Might circular reasoning explain the clinical differences between the two entities, as the decision to include a patient with axial involvement in either the axSpA or the PsA cohort might be influenced by age or additional peripheral features? Although this issue might partly be valid, some important findings point to additional genetic differences between axSpA+Pso and axial PsA, besides HLA-B27. First, the proportion of patients with a positive family history of axSpA on the one hand and the proportion of those with a positive family history of PsA and psoriasis on the other hand differed significantly between the two disorders, even in HLA-B27 positive individuals. Second, the presence of obesity was significantly higher in axial PsA than in axSpA+pso. A large-scale cross-trait genetic correlation analysis of psoriasis with multiple diseases has recently shown a significant association of psoriasis with obesity.23 Taken together, these findings might indicate differences in underlying genetic correlations between axSpA and PsA.
Strengths of our analysis include the large number of patients with axSpA+pso and axial PsA across the whole spectrum of radiographic involvement recruited in a real-life observational registry by rheumatologists from private practices and secondary and tertiary institutions.24 Patients in both cohorts were assessed according to comparable protocols by the same rheumatologists. We also acknowledge important limitations. There is no validated definition of axial PsA and we have chosen the expert opinion of the treating rheumatologist with regard to axial involvement. Additional information was available regarding back pain of at least 3 months duration, IBP as well as the imaging results that might have influenced the decision. Bath Indices for disease activity and severity of axial involvement were only available for a minority of patients in the PsA cohort. Imaging data were not collected to confirm the pattern of X-ray and MRI involvement indicated by the rheumatologist and/or to indicate alternative reasons for back pain (eg, degenerative changes).
In conclusion, we confirm demographic, clinical and genetic differences between axSpA and axial PsA, even when axSpA with concomitant psoriasis is used for the comparison.
Data availability statement
Data may be obtained from a third party and are not publicly available. Restrictions apply to the availability of these data. Data are owned by a third party, the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) foundation. Data may be obtained after approval and permission from the license holder (SCQM). Contact information for data requests: scqm@hin.ch.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by The Ethics committee of the Canton of Zurich (BASEC 2022-00272). Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We thank all rheumatologists and their patients for participation to SCQM and the entire SCQM staff for the continuous support. A list of rheumatology practices and hospitals contributing to the SCQM registries can be found at: http://www.scqm.ch/institutions.
References
Footnotes
Twitter @ramicheroli
Contributors AC and RM conceptualised and designed the study. AC, BM, KB, MSN, PE and RM substantially contributed to the acquisition of clinical data. AG, AB, SK and AS processed the data and performed the statistical analyses. All authors contributed to the interpretation of the data. AC wrote the article, and all coauthors revised the manuscript critically for important intellectual content. All authors agreed on the final content of the submitted manuscript. AC accepts full responsibility for the work and the conduct of the analyses, had access to the data, and controlled the decision to publish.
Funding This study was financially supported by Eli Lilly. Eli Lilly had no role in the study design or in the collection, analysis or interpretation of the data, the writing of the manuscript or the decision to submit the manuscript for publication. Publication of this article was not contingent on approval by Eli Lilly.
Competing interests The SCQM foundation is supported by the Swiss Society of Rheumatology and by Abbvie, AstraZeneca, Biogen, iQone, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Samsung Bioepis, Sandoz. AC received honoraria for lectures or presentations from AbbVie, Merck Sharp & Dohme and Novartis. AG and SK are employees of SCQM and part of their salary in relation to statistical work performed for this study was financed through a research grant from Eli Lilly to SCQM (see funding). AS received consulting fees from Pfizer and support for attending meetings from Gilead. BM received speaking fees from Janssen, Eli Lilly, Novartis and Pfizer, support for attending meetings from Janssen and Pfizer and a research grant from Celgene. MSN received consulting and/or speaking fees from Abbvie, Eli Lilly, Janssen, Novartis and Pfizer, a research grant from Novartis. PE received financial support from UCB for attending a meeting. RM received honoraria for lectures or presentations from Abbvie, Eli Lilly, Janssen, Gilead and Pfizer. AB and KB declare they have no conflicts of interest.
Provenance and peer review Not commissioned; externally peer reviewed.