Effect of abatacept on bone in patients with psoriatic arthritis—results from a prospective interventional high-resolution imaging study (ABEPSA)

Abstract

Objectives

Abatacept (ABA) is a selective costimulation modulator that inhibits T cell activation. It is approved for rheumatoid arthritis (RA) and psoriatic arthritis (PsA). While its efficacy in RA is well established, its effect on structural joint damage in PsA remains uncertain. This study evaluated the effects of ABA on erosive and proliferative bone changes in PsA using high-resolution peripheral quantitative computed tomography (HR-pQCT) over 24 weeks.

Methods

ABA bone effects in PsA with bone biomarkers is a prospective, single-arm, open-label, phase IV trial including patients with active PsA (≥2 swollen/tender joints and ≥1 hand joint erosion at baseline). Participants received weekly subcutaneous ABA (125 mg) for 24 weeks; those with good clinical response at week 12 continued treatment. Bone changes were assessed by HR-pQCT and magnetic resonance imaging (MRI) at baseline and week 24. The primary endpoint was change in erosion volume.

Results

Fifteen patients (mean age 59.5 ± 9 years) were enrolled; 8 continued treatment through week 24. ABA led to a reduction in clinical disease activity. Imaging showed no new erosions or significant erosion progression, and no new structural entheseal lesions on HR-pQCT or MRI. Inflammatory MRI changes persisted in some cases. ABA was well tolerated with no new safety signals.

Conclusions

ABA prevented new erosions and structural entheseal lesions over 24 weeks, indicating a potential osteoprotective effect. These results suggest ABA may modulate bone remodelling in PsA and help preserve joint structure alongside clinical improvements.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

• •Abatacept (ABA) is an established treatment for rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
• •Its immunomodulatory effect on T-cell activation contributes to clinical improvement in PsA.
• •The impact of ABA on structural bone changes in PsA, particularly on erosive and proliferative lesions, has not been well characterized.

WHAT THIS STUDY ADDS

• •Using high-resolution peripheral quantitative computed tomography (HR-pQCT), this study quantitatively assessed erosive and proliferative bone changes in PsA over 24 weeks of ABA treatment.
• •ABA stabilized existing erosions and reduced progression of bone proliferation at the metacarpophalangeal joints.
• •The findings provide in vivo evidence of ABA's potential to limit structural joint damage in PsA.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• •HR-pQCT offers a sensitive imaging approach for detecting early structural responses to targeted therapies in PsA.
• •ABA may be considered as a disease-modifying option for patients with erosive or bone-proliferative PsA phenotypes.
• •The results support further long-term imaging and mechanistic studies on T-cell–directed therapies in PsA.

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INTRODUCTION

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by joint, entheseal, and skin involvement, affecting up to 30% of patients with psoriasis [1,2]. Beyond joint and entheseal inflammation, PsA can lead to structural damage, manifested by bone erosions and new bone formation (structural entheseal lesions [SELs]), which contribute significantly to functional impairment and reduced quality of life in PsA patients [3]. Early intervention to control inflammation and limit structural damage is therefore critical in the management of PsA [4].

Although treatment of PsA traditionally includes nonsteroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs (DMARDs) are the central pillar of today’s management of PsA [5]. Monoclonal antibodies, especially those against tumour necrosis factor (TNF) alpha, interleukin (IL)-17, and IL-23, have substantially improved the treatment of PsA, showing clinical and structural benefits when used in PsA patients. Although the selective T cell costimulation inhibitor abatacept (ABA) has also been approved for the treatment of PsA, substantially fewer data are available on its efficacy and structural effects compared with other biologics, particularly TNF and IL inhibitors [6,7]. It is unknown to what extent ABA prevents structural damage in PsA, as the radiographic outcomes in the phase III study with ABA in PsA showed very little radiographic progression and no difference between ABA and placebo [6]. In contrast, ABA has shown protective effects on bone structure in patients with rheumatoid arthritis (RA), where ABA has also been approved and where radiographic studies have been conducted to assess the structure-sparing effect of ABA [8].

As traditional radiographic studies that aim to show structural benefits of anti-inflammatory drugs in arthritis are large and expensive, and the overall progression rate of bone changes in conventional radiographs in PsA patients is small to minimal, it is unlikely that structural effects of ABA in PsA will be detected using radiography alone. In contrast, high-resolution peripheral quantitative computed tomography (HR-pQCT) represents a sensitive method for detecting and quantifying peripheral bone erosions in RA and PsA [[9], [10], [11], [12], [13], [14], [15], [16]]. HR-pQCT has been extensively utilised in arthritis research to evaluate changes in bone microstructure and erosions. Notably, it has served as a primary endpoint in assessing longitudinal bone effects of DMARDs, demonstrating improvements in bone properties and biomechanics in patients with RA receiving targeted therapies [11]. Accordingly, HR-pQCT may provide a feasible approach to test the effect of ABA on bone erosion development and progression in a smaller setting in order to understand whether the anti-inflammatory effect of the drug in PsA could be accompanied by a protection of bone structure.

This observational study aimed to evaluate the impact of ABA on bone erosions and new bone formation in PsA patients by means of HR-pQCT over a 24-week period. In addition, the clinical effects of ABA in patients were recorded and the effects of inflammation were assessed by magnetic resonance imaging (MRI) of the hands.

METHODS

Study design and participant selection

This prospective, single-arm, single-centre, open-label, phase 4 interventional trial (EudraCT: 2017-002793-39) was designed to evaluate the effects of ABA on bone erosion and inflammation in patients with active PsA over 24 weeks. Eligible patients had active PsA, defined by ≥2 swollen and tender joints and at least 1 hand joint erosion on baseline imaging. These criteria ensured the inclusion of patients with both clinically and radiographically active PsA, appropriate for assessing the effects of ABA on bone erosions and inflammation. The study protocol was approved by the institutional review board of the Universitätsklinikum Erlangen (#361_17) and the Paul Ehrlich Institute. Written informed consent was obtained from all participants prior to enrolment. In this study, the term sex refers to biological attributes (male or female) as recorded in patient medical records.

All participants received subcutaneous ABA at a dose of 125 mg weekly for 24 weeks. Treatment response was assessed at 12 weeks using the Disease Activity Score 28 based on erythrocyte sedimentation rate (DAS28-ESR). Nonresponders, defined as patients failing to achieve a DAS28-ESR reduction of at least 1.2 after 12 weeks, were discontinued from the study at this interim evaluation.

The primary endpoint of the study was the change in joint erosion volume, assessed using HR-pQCT. Secondary endpoints included SELs, evaluated by both HR-pQCT and MRI, as well as other MRI measures of inflammation and structural damage using the Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS), alongside clinical assessments.

Clinical assessments

Clinical disease activity of PsA was tested by the following parameters and composite scores: tender joint count (TJC), swollen joint count (SJC), DAS28-ESR, Disease Activity in Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis score, Maastricht Ankylosing Spondylitis Enthesitis Score, Psoriasis Area and Severity Index (PASI), Health Assessment Questionnaire Disability Index (HAQ-DI), and Psoriatic Arthritis Impact of Disease (PsAID).

HR-pQCT

HR-pQCT was used to assess bone erosions in finger joints. This imaging technique allows for high-resolution 3-dimensional evaluation of trabecular and cortical bone. The first-generation HR-pQCT scanner, XtremeCT (Scanco Medical AG), acquires in vivo images at 82 μm voxel size [17].

Erosions were evaluated at baseline and at week 24 in the second and third metacarpophalangeal (MCP) joints. Erosion assessment included the number of erosions and volume. Erosion segmentation was performed manually using a standardised protocol: first, erosions were identified visually on HR-pQCT slices (eg, the largest erosion per joint selected as the target erosion); then, a manually defined region of interest was applied to delineate the erosion volume within the cortical shell. The total erosion volume (in mm³) per joint was computed by summing voxel volumes within each segmented slice. SELs—defined as bone proliferations at entheseal insertion sites—were also assessed using the same scans. All imaging procedures followed the technical standards for acquisition and analysis of HR-pQCT as defined in published guidelines [[9], [10], [11]].

Magnetic resonance imaging

MRI of the dominant hand was performed using a Siemens MAGNETOM Aera 1.5T system (Siemens) to evaluate inflammatory changes, including synovitis, tenosynovitis, and osteitis. Patients were scanned in a prone position with the hand extended overhead. The imaging protocol included the following sequences: coronal: T1 turbo spin echo (TSE), T2 turbo inversion recovery magnitude (TIRM), and T1 TSE fat-saturated (contrast-enhanced); transversal: T2 TSE fat-saturated and T1 TSE fat-saturated (contrast-enhanced). Inflammatory changes were scored using the PsAMRIS instrument, a validated scoring system for quantifying bone and soft tissue inflammation [18,19]. MRI assessments focused on the MCP, proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of the second to fifth fingers. Synovitis, tenosynovitis, and bone oedema scores were graded on a 0-3 scale per joint, yielding a total score range of 0-72 for each feature across the 24 assessed joints. Bone erosion was scored on a 0-10 scale per joint, resulting in a total score range of 0-240. Higher scores indicate more severe pathology. Periarticular inflammation and bone proliferation were recorded as either present or absent. MRI assessments included the PsAMRIS total inflammation score, which was calculated as the sum of the scores of synovitis, tenosynovitis, bone marrow oedema, and periarticular inflammation [19]. New erosions were counted separately. All MRI images were evaluated by an independent, blinded reader (MY-M) following Outcome Measures in Rheumatology (OMERACT) pathology definitions, ensuring standardised interpretation of imaging findings.

Statistical analysis

For each clinical and imaging outcome, linear mixed-effects models (LMMs) were used to assess changes from baseline. LMMs were chosen to account for within-subject correlations due to repeated measurements over time and to handle missing data more flexibly than traditional repeated-measures analysis of variance (ANOVA). Patient identification was included as a random intercept to account for individual variability and within-patient correlation of observations. Estimated marginal means from these regression models were calculated using the emmeans package, providing 95% CIs for mean scores and mean changes. No missing data imputation was used. All P values are 2-sided and considered significant when less than .05. Data preparation, statistical modelling, and visualisation were performed using R version 4.4.1. The key packages used for analysis were the lme4, tidyverse, and broom.mixed.

RESULTS

Patient inclusion, baseline demographics, and safety results

Among the 20 patients screened, 15 met eligibility criteria and were enrolled in the study. Of these, 13 completed following visits per protocol, with 8 patients reaching the end of the study as responders. Five patients were classified as nonresponders, leading to early termination due to insufficient improvement by week 12 and no further follow-up (Fig 1). Additionally, 2 patients were discontinued early due to worsening PsA and an adverse event (AE). Baseline demographic and clinical characteristics of the patients are shown in Table 1. Patients had a mean age of 60 years (SD, 9) and a balanced sex distribution with 6 males and 7 females. The mean body mass index was 31.11 kg/m² (SD, 5.34). These characteristics were similar across both responders and nonresponders, ensuring baseline comparability between groups (Table 1).

Figure 1.

Flowchart illustrating the disposition of participants through the study phases. DAS28-ESR, Disease Activity Score 28 based on erythrocyte sedimentation rate; EoS, End of Study.

Table 1.

Baseline characteristics

Variables	Nonresponder (N = 5)	Responder (N = 8)	Overall (N = 13)
Male sex	2 (40.0%)	4 (50.0%)	6 (46.2%)
Age (y)	60.20 (6.53)	59.12 (10.74)	59.54 (9.04)
BMI (kg/m²)	32.52 (7.49)	30.22 (3.80)	31.11 (5.34)
DAS28 (ESR)	4.87 (0.79)	4.84 (0.84)	4.85 (0.79)
TJC	11.80 (5.07)	6.50 (2.51)	8.54 (4.41)
SJC	5.60 (4.72)	4.38 (2.13)	4.85 (3.24)
SPARCC	3.00 (2.35)	1.38 (1.19)	2.00 (1.83)
LEI	1.00 (1.22)	0.75 (0.71)	0.85 (0.90)
MASES	1.00 (1.41)	0.12 (0.35)	0.46 (0.97)
PASI	2.86 (4.33)	3.65 (5.45)	3.35 (4.87)
Previous medications
csDMARDs	4 (80.0%)	8 (100.0%)	12 (92.3%)
bDMARDs	2 (40.0%)	2 (25.0%)	4 (30.8%)
tsDMARDs	2 (40.0%)	3 (37.5%)	5 (38.5%)
Concomitant Medication
csDMARDs	4 (80.0%)	8 (100.0%)	12 (92.3%)
Glucocorticoids	2 (40.0%)	2 (25.0%)	4 (30.8%)
Topical treatments	1 (20.0%)	5 (62.5%)	6 (46.2%)

bDMARD, biologic disease-modifying antirheumatic drug; BMI, body mass index; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DAS28, Disease Activity Score 28; ESR, erythrocyte sedimentation rate; LEI, Leeds Enthesitis Index; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; PASI, Psoriasis Area and Severity Index; SJC, swollen joint count; SPARCC, Spondyloarthritis Research Consortium of Canada enthesitis score; TJC, tender joint count; tsDMARD, targeted synthetic disease-modifying antirheumatic drug.

Of the 15 participants, 9 reported AEs, mostly mild to moderate, including infections, skin disorders, musculoskeletal symptoms, and metabolic disturbances. One serious AE (distal radius fracture) was unrelated to ABA and fully resolved. No new safety signals emerged, and no dose modifications were needed. Two participants discontinued treatment: one due to PsA worsening (reasonably related to ABA) and another due to elevated gamma-glutamyl transferase (GGT) levels (unrelated). Some psoriasis-related lesions were classified as treatment-related, whereas hypertension, tachycardia, and metabolic disturbances were classified as unrelated. Overall, ABA was well tolerated, with most AEs resolving without intervention.

HR-pQCT findings

Based on HR-pQCT assessment, over the 24-week treatment period, no new erosions were observed, suggesting that ABA may potentially protect from the development of bone erosion in PsA patients. Additionally, no new SELs were detected, further supporting a bone-protective effect of ABA. In terms of erosion volume, the mean baseline measurement across assessed joints was 5.84 mm³ (SD = 11.31), which increased slightly to 6.56 mm³ (SD = 11.68) by week 24. This mean change of 0.71 mm³ (95% CI, −1.53 to 2.95) was not statistically significant (P = .504). One responder could not be assessed for erosion volume due to severe MCP joint destruction. Excluding patients with missing data, responders generally maintained stable erosion volumes from baseline to week 24. Individual changes in erosion volume are depicted in Figure 2. A representative case is shown in Figure 3: panel A displays the baseline erosion volume of 42.88 mm³ at the third MCP joint, whereas panel B shows the same erosion at week 24 with a reduced volume of 40.72 mm³, corresponding to a change of −2.16 mm³. This patient exhibited the largest baseline erosion within the cohort. Notably, the overall volume changes observed across patients reflect modifications in existing erosions rather than the formation of new lesions, indicating that ABA may contribute to stabilising structural integrity in PsA patients.

Figure 2.

Changes in bone erosion volume from baseline to week 24 stratified by metacarpophalangeal joint and treatment response. The figure illustrates the trajectory of bone erosion volumes (mm³) at baseline and at week 24 for different metacarpophalangeal (MCP) joints (MCP-2 and MCP-3) in responders (blue) and nonresponders (red). Solid and dashed lines represent distinct MCP joints, with separate trends shown for responders and nonresponders. Data highlight differences in erosion volume progression over time, emphasising distinct response patterns to intervention.

Figure 3.

Representative example of erosion volume change in a responder patient. Panel A shows the baseline erosion volume at the third metacarpophalangeal joint (MCP3), quantified as 42.88 mm³. Panel B displays the same erosion at week 24, with a reduced volume of 40.72 mm³. The total change was −2.16 mm³. This patient had the largest baseline erosion in the cohort.

MRI findings

MRI-based PsAMRIS scores provided additional insights into the effects of ABA on inflammation. Synovitis scores in responders increased significantly from 2.83 units (95% CI, −1.57 to 7.23) at baseline to 5.33 units (95% CI, 0.93 to 9.73) at week 24 (mean change, +2.5; 95% CI, 0.54 to 4.46, P = .018), indicating limited control of synovitis in this cohort. In contrast, tenosynovitis showed a nonsignificant decrease. Other MRI markers, including bone marrow oedema, bone erosions, and bone proliferations, remained stable, supporting HR-pQCT data (Table 2; see also Fig 4 for longitudinal changes in imaging outcomes).

Table 2.

Changes in MRI parameters

Variable	Baseline (95% CI)	Wk 12 (95% CI)	Wk 24 (95% CI)	Change (95% CI) BL-W12	P BL-W12	Change (95% CI) BL-W24	P BL-W24
N erosions	5.3 (1.0; 11)	5.4 (0.9; 12)	5.6 (0.7; 12)	0.1 (−0.2; 0.5)	.429	0.3 (−0.1; 0.7)	.111
PsAMRIS bone marrow oedema	2.6 (3.4; 8.5)	3.8 (2.1; 9.8)	3.57 (2.4; 9.5)	1.27 (−0.9; 3.4)	.218	1.0 (−1.0; 3.0)	.298
PsAMRIS bone erosion	1.7 (0.5; 3.9)	1.9 (0.3; 4.0)	1.86 (0.3; 4.0)	0.2 (−0.1; 0.4)	.251	0.1 (−0.1; 0.4)	.264
Bony proliferations	4.4 (1.7; 7.1)	4.6 (1.9; 7.3)	4.57 (1.9; 7.3)	0.2 (−0.1; 0.4)	.250	0.1 (−0.1; 0.4)	.264
PsAMRIS total inflammation	8.7 (7.5; 29)	10 (−5.5; 27)	11 (4.8; 28)	2.0 (−0.6; 4.7)	.112	2.7 (0.2; 5.1)	.036
PsAMRIS synovitis	2.8 (1.6; 7.2)	3.9 (0.6; 8.3)	5.3 (0.9; 9.7)	1.0 (−1.1; 3.1)	.294	2.5 (0.5; 4.5)	.018
Tenosynovitis	1.2 (0.3; 2.6)	0.8 (0.8; 2.3)	0.2 (1.3; 1.6)	−0.4 (−2.4; 1.6)	.668	−1.0 (−2.9; 0.9)	.274
Tenosynovitis Ext-Flex	2.0 (0.2; 3.8)	1.4 (0.5; 3.4)	0.7 (1.1; 2.5)	−0.6 (−2.8; 1.6)	.569	−1.3 (−3.4; 0.8)	.185

BL–W12 and BL–W24 refer to changes from baseline to week 12 and baseline to week 24, respectively. MRI, magnetic resonance imaging; PsAMRIS, Psoriatic Arthritis Magnetic Resonance Imaging Score; Tenosynovitis score (Ext/Flex), tenosynovitis score of the extensor and flexor tendon compartments. Bold values indicate statistically significant results (p < 0.05).

Figure 4.

Standardised mean change from baseline among responders at weeks 12 and 24. Each point represents the standardised mean change in clinical, patient-reported, or imaging outcomes from baseline, calculated among treatment responders. Variables were standardised (mean = 0, SD = 1) based on baseline values to enable cross-variable comparison despite differing original scales. Negative values indicate improvement for outcomes where lower scores reflect better status (eg, disease activity, pain). CRP, C-reactive protein; DAPSA, Disease Activity in Psoriatic Arthritis; DAS28, Disease Activity Score 28; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; MRI, magnetic resonance imaging; PASI, Psoriasis Area and Severity Index; PsAID, Psoriatic Arthritis Impact of Disease; PsAMRIS, Psoriatic Arthritis Magnetic Resonance Imaging Score; SPARCC, Spondyloarthritis Research Consortium of Canada enthesitis score; Tenosynovitis score (Ext/Flex), tenosynovitis score of the extensor and flexor tendon compartments; VAS, visual analogue scale.

Clinical outcomes

Responders showed substantial reductions in disease activity, with the DAS28-ESR decreasing from 4.84 (95% CI, 4.15 to 5.54) at baseline to 2.75 (95% CI, 2.05 to 3.44) at week 24, with a mean reduction of −2.09 (95% CI, −2.61 to −1.58, P < .001), which aligns with the European Alliance of Associations for Rheumatology (EULAR) response criterion of a DAS28-ESR improvement of ≥1.2 used to define good responders [20]. DAS28-C-reactive protein (CRP) showed a nearly identical pattern of improvement. Similarly, DAPSA scores dropped from 27.83 (95% CI, 22.08 to 33.57) to 9.88 (95% CI, 4.14 to 15.62), indicating significant disease control in those continuing treatment with ABA after week 12. Five out of 8 patients (62.5%) had minimal disease activity (MDA) scores that became positive compared with baseline. Both tender and swollen joint counts showed significant reductions in the responders. The number of TJC as per DAS28 decreased from 6.5 joints (95% CI, 4.96 to 8.04) at baseline to 1.13 joints (95% CI, −0.41 to 2.66) by week 24, with a mean reduction of −5.38 (95% CI, −7.03 to −3.72, P < .001). SJC also declined significantly, confirming the clinical benefits of ABA in reducing joint inflammation.

Responders reported marked improvements in pain and quality of life. Visual analogue scale (VAS) pain scores dropped significantly from 57.8 mm (95% CI, 43.5 to 72.0) at baseline to 33.1 (95% CI, 18.9 to 47.4) by week 24, with a mean change of −24.6 (95% CI, −44.5 to −4.7, P = .019). Enthesitis improved significantly over the study period, as reflected by a reduction in both SPARCC (−1.12, 95% CI, −1.84 to −0.41, P = .005) and LEI scores (−0.75, 95% CI, −1.19 to −0.31, P = .003), suggesting a meaningful reduction in enthesitis-related inflammation. In contrast, PASI scores did not show a meaningful change over time (−0.16, 95% CI, −3.66 to 3.33, P = .922), confirming previous observations that ABA had a limited effect on skin manifestations. HAQ-DI and PsAID scores showed slight, nonsignificant improvements, indicating a trend towards better functionality and quality of life. Detailed clinical outcomes are provided in Table 3, whereas the mean changes in clinical and imaging parameters over time for responders are illustrated in Figure 3.

Table 3.

Clinical measures

Variable	Baseline (95% CI)	Week 12 (95% CI)	Week 24 (95% CI)	Change (95% CI) BL-W12	P BL-W12	Change (95% CI) BL-W24	P BL-W24
DAS28-ESR (units)	4.8 (4.2; 5.5)	2.9 (2.3; 3.6)	2.8 (2.1; 3.4)	−1.9 (−2.4; −1.4)	<.001	−2.1 (−2.6; −1.6)	<.001
DAS28-CRP (units)	4.4 (3.7; 5.1)	2.7 (2.0; 3.4)	2.5 (1.8; 3.2)	−1.8 (−2.3; −1.3)	<.001	−1.9 (−2.4; −1.4)	<.001
VAS pain (mm)	58 (44; 172)	32 (17; 46)	33 (19; 47)	−26 (−46; −5.8)	.015	−24 (−44; −4.7)	.019
VAS Global (mm)	58 (42; 73)	37 (21; 53)	36 (20; 52)	−21 (−43; 1.6)	.067	−22 (−44; 0.6)	.056
VAS Physician (mm)	53 (39; 67)	22 (7.7; 30)	18 (4.0; 32)	−31 (−51; −11)	.005	−35 (−55; −15)	.002
TJC 28 (N)	6.5 (5.0; 8.0)	1.1 (0.4; 2.7)	1.1 (0.4; 2.7)	−5.4 (−7.0; −3.7)	<.001	−5.4 (−7.0; −3.7)	<.001
SJC 28 (N)	4.4 (2.9; 5.9)	1.4 (0.2; 2.9)	0.6 (0.9; 2.2)	−3.0 (−4.5; −1.5)	.001	−3.8 (−5.3; −2.2)	<.001
DAPSA (units)	28 (22; 34)	13 (7.0; 19)	9.9 (4.1; 16)	−15 (−22; −8.4)	<.001	−18 (−25; −11)	<.001
TJC-DAPSA (N)	9.4 (7.0; 12)	2.6 (0.2; 5.0)	1.6 (0.8; 4.0)	−6.8 (−9.5; −4.0)	<.001	−7.8 (−10; −5.0)	<.001
SJC-DAPSA (N)	5.6 (3.8; 7.5)	2 (0.2; 3.9)	0.6 (−1.2; 2.5)	−3.6 (−5.8; −1.5)	.003	−5 (−7.2; −2.8)	<.001
CRP (mg/dL)	1.1 (0.2; 2.0)	1.0 (0.1; 1.9)	0.5 (−0.4; 1.4)	−0.1 (−0.8; 0.7)	.790	−0.6 (−1.3; 0.2)	.125
HAQ-DI (units)	0.6 (0.2; 0.9)	0.3 (0.0; 0.6)	0.4 (0.1; 0.7)	−0.2 (−0.6; 0.1)	.160	−0.2 (−0.5; 0.2)	.339
SPARCC (units)	1.4 (0.5; 2.3)	0.9 (0.0; 1.8)	0.3 (−0.7; 1.2)	−0.5 (−1.2; 0.2)	.157	−1.1 (−1.8; −0.4)	.005
LEI (units)	0.8 (0.4; 1.1)	0.25 (0.1; 0.6)	0 (−0.4; 0.4)	−0.5 (−0.9; −0.1)	.028	−0.8 (−1.2; −0.3)	.003
MASES (units)	0.1 (0.4,0.6)	0.5 (0.0; 1.0)	0.1(0.4; 0.6)	0.4 (−0.2; 1.0)	.211	0 (−0.6; 0.6)	<.999
PsAID (units)	3.0 (2.0; 3.9)	2.3 (1.3; 3.2)	2.3 (1.3; 3.2)	−0.7 (−2.1; 0.7)	.290	−0.7 (−2.1; 0.7)	.298
PASI (units)	3.7 (0.8; 6.5)	1.2 (1.7; 4.0)	3.5 (0.6; 6.4)	−2.5 (−6; 1)	.147	−0.2 (−3.7; 3.3)	.922

BL–W12 and BL–W24 refer to changes from baseline to week 12 and baseline to week 24, respectively. CRP, C-reactive protein; DAPSA, Disease Activity in Psoriatic Arthritis; DAS28-CRP, Disease Activity Score 28 based on C-reactive protein; DAS28-ESR, Disease Activity Score 28 based on erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; MASES, Maastricht Ankylosing Spondylitis Enthesitis Score; PASI, Psoriasis Area and Severity Index; PsAID, Psoriatic Arthritis Impact of Disease; SJC, swollen joint count; SPARCC, Spondyloarthritis Research Consortium of Canada enthesitis score; TJC, tender joint count; VAS, visual analogue scale. Bold values indicate statistically significant results (p < 0.05).

DISCUSSION

This small interventional study with high-sensitivity bone imaging shows that ABA may potentially protect from progression of bone erosions and SELs in patients with active PsA. PsA patients treated with ABA showed no new bone erosions or SELs in high-resolution CT scans that can detect bone erosions as small as 82 µm in diameter [17]. As a 3-dimensional, high-resolution technique, HR-pQCT can detect even small bone lesions in the joints, exceeding even the sensitivity of MRI [21].

Hence, these data suggest that ABA may effectively prevent progression of structural damage, as bone erosions, bone marrow oedema, and bone proliferations remained stable across MCP, PIP, and DIP joints. However, synovitis scores increased significantly during treatment, although the confidence intervals were wide. This suggests that while the effect is statistically significant, the magnitude of increase varies, possibly reflecting heterogeneous inflammatory activity or measurement variability. In contrast, tenosynovitis tended to decrease, but this change was not statistically significant, again indicating individual variability. Overall, although ABA appears to stabilise structural damage, its control of imaging-defined synovial inflammation remains limited in some patients.

In addition, we have not observed any significant increase in erosion volume in HR-pQCT data in ABA-treated PsA patients, suggesting no progression of existing damage, which was also found in the quantification of MRI erosions. Furthermore, SELs, which are often the leading localised bone pathology in PsA, did not progress. These data support the concept that ABA prevents bone damage in PsA. The data also provide additional insights into the phase 3 Active-Controlled Study of Abatacept versus Adalimumab in Biological-Naïve Patients with Psoriatic Arthritis (ASTRAEA) trial on ABA in PsA, which showed very little radiographic progression and no difference between ABA and PBO [6]. As conventional radiographs are relatively insensitive for detecting structural progression, it remains unclear to what extent ABA protects the bone in PsA, particularly with regard to small entheseal proliferations. This small study using highly sensitive 3-dimensional imaging instruments as confirmatory techniques did not show progression of structural damage. Hence, the structure-sparing effect of ABA in PsA may have been underestimated. EULAR recommendations on the treatment of PsA state that the structural effects of ABA in PsA on bone erosions may be relatively modest, as the radiographic data did not show differences between the drug and PBO [6,22]. However, our new data indicate that even with a high-resolution technique to analyse bone, no progression of structural damage can be detected. This effect may be related to osteoclast inhibition reported for ABA as previously shown [23]. In addition, ABA was generally well tolerated, with most adverse events being mild or moderate, and no new safety concerns were observed. Although these data confirm the efficacy and safety of ABA in PsA, the breadth of effect of ABA in PsA seems to be narrower than that of other biologic DMARDs, which show strong efficacy on both skin and musculoskeletal components of the disease [5]. In accordance, ABA not only lowered PASI scores in this study but also did not significantly lower HAQ and PsAID scores. Furthermore, no significant decline in MRI synovitis score was noted with ABA. Synovitis scores even increased by a mean of 2.5 units, which, however, only marginally exceeds the smallest detectable difference of 2.01 units reported by McQueen et al [24], indicating it likely falls within measurement variability and is not clinically meaningful. In support of this conclusion, PsAMRIS validation studies show the efficacy of ABA in reducing synovitis and tenosynovitis scores [18]. On the contrary, a synovial biopsy study has shown that ABA decreases regulatory T cells in the synovium of PsA patients which could limit its anti-inflammatory effects in the joints [25]. Thus, although the observed increase in synovitis scores may appear notable, its proximity to the smallest detectable difference and the likely presence of wide confidence intervals make it difficult to interpret this change as clinically meaningful. This interpretation is further supported by the fact that other MRI parameters, such as tenosynovitis, also showed nonsignificant changes, including both increases and decreases.

The discrepancy between stable bone structure and increased synovitis scores may reflect the specific mode of action of ABA. Although ABA interferes with T cell costimulation and may directly inhibit osteoclast activation [23], thereby stabilising bone lesions, its anti-inflammatory effect on synovial tissue may be weaker than that of cytokine-blocking biologics. This could explain why erosions and entheseal lesions remained stable despite persistent or even increasing synovitis on MRI. Furthermore, the observed increase in synovitis was modest, with wide confidence intervals and close to the smallest detectable difference reported for PsAMRIS, raising the possibility that this change reflects variability rather than a clinically meaningful signal. Notably, these findings were obtained in patients who showed a clinical response to ABA, with the majority reaching MDA.

This study is limited by its small sample size, which reduces the robustness of the findings. Confirmation in larger controlled cohorts is warranted. In addition, the observation period of 24 weeks may be too short to fully capture structural progression in PsA. Nevertheless, due to the high sensitivity of HR-pQCT erosion volume measurements, even short-term changes can be detected and the study still provides important insights into treatment effects on bone structure. Indeed, previous work has demonstrated that HR-pQCT-based quantification of erosion volume is highly reproducible and can identify both progression and repair of erosions within 12 months of treatment in inflammatory arthritis [26]. Thus, although our study cannot exclude long-term structural progression, the absence of measurable changes in erosion volume within 24 weeks supports the notion that ABA stabilises structural lesions in PsA in the short term. Longer-term follow-up in larger cohorts will be required to confirm whether this stabilising effect is sustained. HR-pQCT follow-up scans were not obtained for nonresponders, as these patients switched therapy after week 12, precluding evaluation of ABA effects in that group. Imaging follow-up was therefore restricted to responders. We assumed that structural response or stabilisation would be much less likely to be achieved without a clinical response; focusing on responders allowed us to specifically investigate whether clinical improvement under ABA was accompanied by stabilisation of bone structure. Thus, our results reflect structural effects within the responder group and are not confounded by the inclusion of nonresponders. Furthermore, disease activity was assessed using DAS28. Although DAS28 is validated for RA and only partially applicable to polyarticular PsA without axial involvement, PsA-specific response criteria such as Psoriatic Arthritis Disease Activity Score (PASDAS) had not yet gained widespread implementation and were not routinely used when the study was designed. DAPSA did not include evaluator (physician) global assessment (EGA), and MDA omitted both CRP and EGA. Given these limitations, DAS28 was considered the most appropriate tool available at the time, particularly as we aimed to include patients with polyarticular PsA. Thus, our conclusions are restricted to ABA-treated PsA patients who achieved a clinical response defined by DAS28; in this cohort, no progression of bone damage was observed, even when assessed with highly sensitive imaging techniques. Comparisons between responders and nonresponders at week 12 revealed that nonresponders had slightly worse outcomes, including higher PASI, PsAID, HAQ-DI, and patient global VAS scores. Additionally, 5 responders achieved MDA by week 12, whereas none of the nonresponders did. These findings support the notion that patient dropouts were clinically justified and that a substantial number of additional responders requiring a second HR-pQCT scan were unlikely to have been missed due to this dropout-related confounder. This conclusion is also supported by 2 independent imaging techniques as both HR-pQCT and MRI analyses show no progression of bone erosion. A further limitation is the lack of a placebo arm. Therefore, clinical responses could have been overestimated. We also do not know whether PsA patients would have progressed in bone lesions during the 6-month observation period by HR-pQCT. However, as no progression was seen even in these highly sensitive imaging techniques a relevant progression of bone damage in ABA responders seems unlikely.

Overall, this study shows that PsA patients responding to ABA did not exhibit progression of bone erosions or SELs over 24 weeks when assessed with sensitive HR-pQCT erosion volume analysis. In consequence, deterioration of bone health appears unlikely in ABA responders in the short term, although this needs confirmation in larger, controlled cohorts.

Editor disclosure

The peer review process did not involve Editorial Board Members David Simon and Arnd Kleyer, and the editorial decision-making was led by editors who were not involved in the creation of this manuscript.