Despite major therapeutic advances, a substantial proportion of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), experience persistent symptoms, functional limitations, and reduced quality of life. Historically, heterogeneous terminology has limited comparability across studies for this population. To address this gap, three international initiatives, GRAPPA, EULAR, and ASAS, have proposed consensus definitions for two nested states: a broad category of “difficult-to-manage” (D2M) or “complex-to-manage” (C2M) disease and a more stringent “treatment-refractory” (TR) subset requiring objective inflammation and multi-mechanism therapeutic failure. This review synthesises these frameworks, highlighting shared principles and key differences. While all definitions adopt a dual-tiered structure, PsA-specific definitions reflect its multidomain nature, incorporating peripheral joints, entheses, skin, nails, axial involvement, and comorbidities; conversely, axSpA definitions are axial-centric, while other domains may play a role in determining D2M/TD disease as well. These distinctions have implications for trial design, biomarker discovery, and management strategies. Harmonisation, prospective validation, and biomarker-driven stratification remain essential to optimise outcomes and advance precision medicine.

Psoriatic arthritis (PsA) presents significant challenges, with many patients experiencing inadequate treatment response. While clinical aspects of suboptimal disease control have been characterized, the emotional burden of treatment failure remains poorly understood. Our objective was to systematically characterize the emotional patterns expressed by PsA patients when describing treatment failures and management challenges. A multi-national online survey with PsA patients was conducted through GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). The survey was conducted to explore their perspectives on how to define complex-to-manage (C2M)-PsA and treatment-refractory (TR-) PsA, and how these conditions impact their lives. Open-ended responses were analyzed using a locally deployed Meta Llama 3.2 3B Instruct large language model, applying Ekman’s six basic emotion framework and the valence-arousal dimensional model. Sentiment analysis revealed predominantly negative emotional patterns (mean valence −0.57 ± 0.25) with moderate-to-high arousal (0.65 ± 0.10). Sadness was most prevalent (54.27

Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, showed efficacy to 2 years in patients with axial spondyloarthritis (axSpA). In this post hoc analysis, we compare the impact of shorter versus longer symptom duration on the efficacy of bimekizumab to Week 104. Efficacy outcomes by symptom duration (≤ 2 [ASAS early axSpA definition] versus > 2 years; ≤ 5 versus > 5 years) were assessed across patients from BE MOBILE 1 and 2 (non-radiographic [NCT03928704]/radiographic axSpA [NCT03928743]) and the combined open-label extension (NCT04436640). (Relative) odds ratios and (relative) differences were calculated to compare 16-week bimekizumab versus placebo treatment effect and 104-week outcomes, and infer the significance of differences, between symptom duration subgroups. Analyses were neither powered for these comparisons nor multiplicity adjusted, and should be interpreted accordingly. Improved disease activity, physical function, fatigue, health-related quality of life and objective signs of inflammation were seen with bimekizumab versus placebo at Week 16 regardless of symptom duration. Outcomes were then sustained or improved with bimekizumab to Week 104 across all subgroups. 16-week bimekizumab versus placebo treatment effect was comparable between subgroups (e.g., ≤ 2-year versus > 2-year symptom duration relative odds ratio [95

OBJECTIVE:To compare clinical features across three axial psoriatic arthritis (PsA) phenotypes: (i) isolated axial PsA, (ii) axial PsA with oligoarticular involvement (axial PsA+oligo), and (iii) axial PsA with polyarticular disease (axial PsA+poly), and assess persistence of first-line biologic and targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs). METHODS:Baseline demographic, clinical, therapeutic, laboratory, and imaging data were retrospectively collected. Kaplan-Meier analysis evaluated treatment persistence, and LASSO Cox regression identified baseline factors associated with discontinuation. RESULTS:Among 621 patients, 175 (28.2%) had isolated axial PsA, 252 (40.6%) axial PsA+oligo, and 194 (31.2%) axial PsA+poly. Psoriasis was more frequent in isolated axial PsA and axial PsA+oligo than in axial PsA+poly (82.3% and 82.1% vs 66.1%; P < 0.001), with lower Human Leukocyte Antigens (HLA)-B27 positivity in axial PsA+poly (10.9% vs 18.9% in isolated axial PsA and 21.6% in axial PsA+oligo; P = 0.02). Sacroiliitis was more frequent in isolated axial PsA (70.3%) and axial PsA+oligo (65.7%) than in axial PsA+poly (53.6%, P < 0.001), whereas spondylitis was more frequent in axial PsA+poly (15.0% vs 8.3% in axial PsA+oligo and 6.3% in isolated axial PsA; P < 0.001). Treatment persistence was longest in axial PsA+oligo (62 months, 95% CI 43-67) and shortest in axial PsA+poly (38 months, 95% CI 24-49) (P = 0.006). Higher VAS global pain was associated with shorter persistence (aHR 1.010, 95% CI 1.003-1.018, P = 0.009), whereas HLA-B27 positivity (aHR 0.56, 95% CI 0.32-0.99, P = 0.045) with longer persistence. CONCLUSION:Treatment persistence in axial PsA varies according to clinical phenotypes, HLA-B27 status and pain, supporting the relevance of phenotypic stratification in clinical practice.

OBJECTIVES:To determine the frequency of axial SpA (axSpA) patients fulfilling the recently proposed Assessment of SpondyloArthritis International Society (ASAS) definitions for difficult-to-manage (D2M) and treatment-refractory (TR) axSpA, and to characterize these patients at initiation of their first advanced therapy. METHODS:Data were derived from the ongoing prospective, multicentre, longitudinal German RABBIT-SpA registry. Patients were eligible if they were biologic and targeted synthetic (b/ts) DMARD-naïve, had initiated a b/tsDMARD and had ≥12 months of follow-up. ASAS definitions were applied to identify cases of D2M and TR. RESULTS:Of 1850 patients with axSpA, 881 (48%) were b/tsDMARD-naïve at the start of observation. A total of 75/881 patients (8.5%) fulfilled the ASAS criteria for D2M and 22/881 (2.5%) additionally met the criteria for TR. At baseline, D2M patients were more frequently female, more often HLA-B27-negative, and more commonly presented with arthritis and enthesitis compared with not-D2M (nD2M) patients. In addition, they exhibited fewer objective inflammatory markers such as elevated CRP or MRI lesions. Opioid use was higher across D2M patients compared with nD2M patients. In the TR group compared with the D2M/nTR, the proportion of female and of obesity was lower. Even at initiation of first-line b/tsDMARD, these patients showed more frequently signs of inflammation, including sacroiliac/spinal MRI lesions and elevated CRP, while peripheral arthritis was less frequent. CONCLUSION:Applying the ASAS definitions in a large real-world cohort identified clinically relevant subgroups with D2M and TR. These findings support their clinical utility and highlight the need for phenotype-specific management strategies.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 annual meeting, held in Bogotá, Colombia, opened with a dedicated trainee symposium that underscored the depth and breadth of emerging talent in psoriatic disease research. This report summarizes the 5 oral presentations and 17 posters encompassing basic, translational, clinical, and outcomes research projects. Together, these works illustrate not only the scientific rigor of the next generation of dermatology and rheumatology investigators but also GRAPPA's expanding global role in driving innovation and advancing the understanding and management of psoriatic diseases.

Objectives To investigate the impact of vitamin D on disease activity, function and health in patients with radiographic axial spondyloarthritis (r-axSpA) undergoing biological disease-modifying antirheumatic drug (bDMARD) therapy.Methods Patients with r-axSpA and active disease at baseline initiating a bDMARD were included in this analysis. Vitamin D (25-hydroxyvitamin D) was measured at baseline and every 6 months until year 2; deficiency was defined as <20 ng/mL. The outcomes were AxSpA Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Patient Global Assessment (PGA), Bath Ankylosing Spondylitis Functional Index (BASFI), Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) and C reactive protein (CRP). Longitudinal associations were evaluated using generalised estimating equations, with sensitivity analyses accounting for time-varying confounders.Results We analysed 122 patients (mean age 36.6 (10.3) years; 66.4% male), of whom 53.3% had vitamin D deficiency at baseline. In longitudinal models, normal vitamin D levels were associated with lower ASDAS (β per 1 ng/mL increase: −0.010; 95% CI −0.017 to −0.003), BASDAI (β: −0.021; 95% CI −0.036 to −0.006), PGA (β: −0.021; 95% CI −0.039 to −0.003) and BASFI (β: −0.015; 95% CI −0.032 to 0.001). Effect estimates of ASDAS, BASDAI, BASFI, CRP (and their corresponding categorical outcomes) were attenuated in sensitivity analyses but remained directionally consistent. Positive associations with PGA and ASAS-HI were also observed though the estimates were not consistent through all models.Conclusions Normal vitamin D levels were modestly associated with lower disease activity in r-axSpA treated with bDMARDs. Monitoring and optimising vitamin D status may support better disease control.

Background Axial disease is a domain of psoriatic arthritis (PsA), referred to as axial-PsA. Despite recent advances and increasing recognition, axial-PsA remains poorly defined; validated classification criteria and longitudinal cohorts are lacking. Objectives We aimed to characterise axial-PsA and delineate phenotypes in an imaging-confirmed cohort. Design GESPIC-axPsA, a dedicated arm of the German Spondyloarthritis Inception Cohort (GESPIC), is a prospective, monocentric, study including patients with psoriasis and clinically diagnosed axial-PsA confirmed by imaging. Baseline assessments included clinical phenotyping, laboratory testing, biosample-collection, radiographs of the axial skeleton, and MRI of the whole spine and sacroiliac joints (SIJs). Methods The analysis was primarily descriptive, characterizing baseline clinical and imaging features of patients with imaging-confirmed axial-PsA; categorical and continuous variables were summarized using appropriate measures based on their distribution, and subgroup comparisons were performed using chi-square or Fisher’s exact tests for categorical variables and Mann–Whitney U tests for continuous variables after assessing normality. Results We enrolled 107 axial-PsA patients (55% female; mean age 44.8 years); 78.5% had active psoriasis, 78.6% had inflammatory back pain (IBP), and 48.6% were HLA-B27 positive. Radiographic sacroiliitis was present in 45.7%. On MRI, active/structural SIJ lesions were seen in 53.3%/73.3%; spinal active/structural lesions in 60.0%/53.3%. Both Classification criteria for axSpA (ASAS) and PsA (CASPAR) were simultaneously fulfilled in 60.7%. We identified 20 patients (18.7%) with spine-only involvement—spinal MRI lesions without SIJ lesions on radiography or MRI. Compared with the remainder, the spine-only group was older, more often female, less frequently HLA-B27–positive, and had back pain less consistent with IBP (all p<0.05). Conclusions In our imaging-confirmed axial-PsA cohort using standardized whole-spine and SIJ MRI, we observed marked phenotypic heterogeneity. Approximately one fifth had isolated spinal involvement; this subgroup differed by age, sex, HLA-B27, and IBP features, with imaging distributions distinct from axSpA—supporting the need for disease-specific classification criteria.

OBJECTIVE:To compare the multisequence standard magnetic resonance imaging (sMRI) protocol of the sacroiliac joints with a single high-resolution deep learning-reconstructed Dixon sequence (DL-Dixon) in patients with suspected axial spondyloarthritis (axSpA). METHODS:Seventy-six patients with chronic low back pain and suspected axSpA underwent clinical, laboratory, and genetic assessment followed by 3T sMRI (T1, T2 fat saturation, volumetric interpolated breath-hold examination, STIR; 19:49 minutes) and high-resolution DL-Dixon imaging (1 mm isotropic; 5:24 minutes). Three blinded readers assessed overall imaging diagnosis, diagnostic confidence, and lesion presence (osteitis, fat metaplasia, erosions, sclerosis, joint space changes). DL was used solely for image reconstruction. The clinical diagnosis served as the reference for diagnostic accuracy; sMRI served as the reference for lesion analysis. Diagnostic accuracy was expressed as the area under the curve (AUC; balanced accuracy). Noninferiority was tested using a predefined margin of 0.05. A decrease of ≤0.05 compared to sMRI was defined as clinically acceptable. RESULTS:Nineteen patients were diagnosed with axSpA. DL-Dixon showed similar diagnostic performance (AUC 0.86 [95% confidence interval (CI) 0.76-0.96]) compared to sMRI (AUC 0.87 [95% CI 0.78-0.96]) and met noninferiority criteria. Interreader agreement was almost perfect for sMRI (κ = 0.81) and substantial for DL-Dixon (κ = 0.71). At the lesion level, DL-Dixon achieved good performance for erosions (AUC 0.83), fat metaplasia (AUC 0.80), and joint space changes (AUC 0.80), and fair performance for osteitis (AUC 0.73) and sclerosis (AUC 0.64). Using DL-Dixon, scan time was reduced by 73%. CONCLUSION:DL-Dixon provides clinically acceptable diagnostic performance while substantially reducing scan time. This approach may improve efficiency and accessibility of MRI for axSpA assessment.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 congress, 2 major research initiatives in psoriatic disease were highlighted: (1) the Axial Involvement in Psoriatic Arthritis (AXIS) study, and (2) the GRAPPA consensus definitions for complex-to-manage psoriatic arthritis (C2M-PsA) and treatment-refractory PsA (TR-PsA). The AXIS study, jointly led by Assessment of SpondyloArthritis international Society (ASAS) and GRAPPA, aims to establish internationally accepted classification criteria for axial PsA. In its recently completed phase, 409 patients were recruited across 41 centers in 19 countries. A comprehensive imaging and clinical dataset were collected and analyzed. The next phase will construct and validate a PsA-specific classification instrument to support future research. In parallel, GRAPPA developed consensus definitions for C2M-PsA and TR-PsA through a transparent, multistakeholder process. C2M-PsA refers to patients with persistent symptoms despite appropriate treatment, often complicated by comorbidities or overlapping conditions. TR-PsA is defined by failure to respond to multiple therapies and by confirmed persistent inflammation. These definitions were endorsed by 95% of GRAPPA members and are supported by practical checklists for clinical use. These initiatives represent a significant advancement in PsA research, offering clinicians structured tools to improve patient stratification, guide treatment decisions, and enhance personalized care.

BACKGROUND:MRI-detected bone marrow oedema in sacroiliac joints is central to diagnosing axial spondyloarthritis, influencing treatment decisions including anti-inflammatory therapy initiation. However, the prevalence of bone marrow oedema in the general population remains unknown, restricting interpretation of MRI findings and potentially leading to overdiagnosis when imaging findings are considered without clinical context. We aimed to establish the prevalence and determinants of sacroiliac bone marrow oedema in the general adult population. METHODS:In this national, population-based, cross-sectional study, we analysed adults aged 20-69 years from the German National Cohort who underwent whole-body MRI between May 1, 2014, and Dec 31, 2016. Three masked experts independently assessed randomly selected participants for sacroiliac bone marrow oedema. The remaining participants were evaluated using a validated deep-learning algorithm that automatically segments and quantifies bone marrow oedema volume from fat-suppressed proton density sequences. We examined associations between the presence of bone marrow oedema (primary outcome) and demographic, lifestyle, and reproductive factors using multivariable logistic regression with sex-stratified analyses to identify differential patterns. There was no patient or public involvement in this study. FINDINGS:Of 11 163 participants (median age 53·0 years [IQR 45·0-61·0], 5432 [48·7%] women and 5731 [51·3%] men), sacroiliac bone marrow oedema was detected in 288 (28·9% [95% CI 26·2-31·9]) of 998 participants analysed by expert readers and 3131 (30·8% [29·9-31·7]) of 10 165 participants analysed by the deep-learning algorithm, approximately 50 times higher than the 0·6% prevalence of self-reported axial spondyloarthritis diagnosis. Bone marrow oedema prevalence was higher in women (33·9% [95% CI 32·6-35·3]) than in men (27·8% [26·6-29·1]; adjusted odds ratio [OR] 1·33 [95% CI 1·23-1·45]). In women, pregnancy history was associated with bone marrow oedema compared with nulliparous women (OR 1·43 [95% CI 1·21-1·71]). In men, age (OR 1·28 per decade [95% CI 1·21-1·35]) and intensive recreational physical activity (1·24 [1·08-1·42]) showed independent associations, whereas age effects were minimal in women (1·16 per decade [1·11-1·23]). Of modifiable risk factors, BMI of 25 kg/m2 and above showed the highest OR (1·62 [1·47-1·79]). Physically demanding occupational work was associated with bone marrow oedema overall (OR 1·25 [95% CI 1·14-1·36]). INTERPRETATION:Sacroiliac bone marrow oedema affects nearly one-third of adults, showing associations with pregnancy, overweight, and occupational physical stress rather than inflammatory disease. This prevalence exceeds self-reported axial spondyloarthritis by 50 times, providing essential population reference data for contextualising MRI findings. These findings show that bone marrow oedema, the key imaging marker for sacroiliitis in Assessment of Spondyloarthritis International Society criteria, commonly occurs from non-inflammatory causes. These population-based data can inform diagnostic interpretation and support development of more specific imaging thresholds to reduce misdiagnosis and inappropriate treatments. FUNDING:Max Kade Foundation and Novartis.

OBJECTIVE:To assess two-year impact of bimekizumab on patient-reported outcomes (PROs), and their association with objective measures of inflammation, in patients with psoriatic arthritis (PsA) who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had tumor necrosis factor inhibitor inadequate response or intolerance (TNFi-IR). METHODS:BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi-IR) were phase 3 studies that assessed subcutaneous bimekizumab 160 mg every four weeks. Both were double-blind, placebo-controlled to week16, then placebo patients switched to bimekizumab. BE OPTIMAL week52 or BE COMPLETE week16 completers could enter BE VITAL (NCT04009499; open-label extension), where all patients received bimekizumab. PROs, disease impact (Psoriatic Arthritis Impact of Disease-12 questionnaire [PsAID-12]), and their association with inflammation (assessed using swollen joint count [SJC]) are reported to year 2. RESULTS:Among 712 bDMARD-naïve and 400 TNFi-IR patients, bimekizumab resulted in long-term sustained improvements in PROs for pain, fatigue, and function (Health Assessment Questionnaire-Disability Index) to year 2. Mean change from baseline (year 2) in bimekizumab-randomized patients for pain and disease impact (PsAID-12) was -33.9 to -29.2 and -2.5 to -2.2, respectively. An achievement of SJC = 0 was associated with the greatest reduction in pain. Decreased SJC was associated with improved pain, fatigue, function, and reduced disease impact to year 2. By year 2, 44.4% to 54.3% of patients originally randomized to placebo or bimekizumab reported no or low disease impact (PsAID-12 ≤1.95), and 88.0% to 92.0% of bimekizumab-randomized patients achieved a patient acceptable symptom state for disease impact (PsAID-12 ≤4), associated with concurrent improvement in SJC and skin involvement. CONCLUSION:Bimekizumab treatment resulted in sustained clinically meaningful improvements in PROs and reduced disease impact to two years in bDMARD-naïve and TNFi-IR patients with PsA. Stringent inflammation control was associated with symptom relief and reduced disease impact.

OBJECTIVE:This study aims to investigate the impact of nonsteroidal anti-inflammatory drug (NSAID) intake on radiographic spinal progression in axial spondyloarthritis (axSpA), considering different NSAID types (COX-2 inhibitors [COX2i] and nonselective NSAIDs [ns-NSAIDs]) and disease subgroups (radiographic [r-axSpA] and nonradiographic [nr-axSpA]). METHODS:Leveraging data from the German Spondyloarthritis Inception Cohort (GESPIC), we conducted analyses on 252 patients with axSpA (139 with nr-axSpA and 113 with r-axSpA), who had minimum two sets of spinal radiographs. The outcome was progression in modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) in two-year intervals. We fitted sequential conditional mean models by using generalized estimating equations and adjusting for longitudinal repeated measures of exposure and time-dependent confounders. We report β-coefficients with 95% confidence intervals (CIs) for outcomes reflecting the progression in mSASSS per 10-point increase in NSAID intake score. RESULTS:At baseline, 201 (80.0%) patients were under NSAID treatment, with 46 (18%) taking COX2i and 156 (62%) taking ns-NSAIDs, and mean total NSAID intake score was 38.3 ± 35.5. A 10-point increase in NSAID intake score was associated with retardation of radiographic progression (β = -0.052, 95% CI: -0.097 to -0.007), with this effect being most pronounced in patients with r-axSpA (β = -0.077, 95% CI: -0.152 to -0.003). COX2i showed a slightly lower point estimate (although not statistically significant) in progression compared to ns-NSAIDs among all patients with axSpA (β = -0.061 and -0.045, respectively). CONCLUSION:Our findings suggest a beneficial effect of higher NSAID intake, particularly COX2i, on slowing radiographic progression in axSpA. These findings may help inform therapeutic strategies, particularly in r-axSpA, although further research is needed for nr-axSpA.

BackgroundAxial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease characterized by pain and stiffness of the axial skeleton, peripheral manifestations like arthritis, dactylitis and enthesitis, extra-musculoskeletal manifestations, and reduced health-related quality of life (HRQoL). Depressive symptoms and fatigue are common, yet few studies have assessed these outcomes at diagnosis and during early treatment.ObjectiveTo evaluate mental health, fatigue, HRQoL, and their association with disease activity and functional status in patients with axSpA at diagnosis and after 1 year of rheumatologic care.MethodsRheuma-VOR is a multicenter, proof- of concept study in Germany implementing structured preselection and early referral for suspected axSpA. We included 238 patients with confirmed axSpA, of whom 76 completed a 12-month follow-up. Disease activity (BASDAI, ASDAS), functional status (BASFI, BASMI, FFbH), mental health (PHQ-9, WHO-5), fatigue (FACIT-F), and HRQoL (EQ-5D) were assessed at baseline and follow-up. Associations between disease activity, function, and patient-reported outcomes (PROs) were analyzed using correlation and multivariable regression.ResultsAt diagnosis, patients exhibited high disease activity (BASDAI 4.6 ± 2.0, ASDAS 2.6 ± 0.9) and substantial prevalence of depressive symptoms (PHQ-9 ≥ 10 in 36.5%) and fatigue (FACIT-F < 39 in 69.5%). One-year follow-up showed significant improvements in disease activity, functional impairment, HRQoL, mental well-being, and fatigue (all p < 0.05). Higher patient-reported disease activity (BASDAI) consistently predicted depressive symptoms and fatigue, whereas functional capacity (FFbH) was the strongest predictor of HRQoL. Physician-assessed disease activity (ASDAS) and functional impairment (BASFI) had smaller or time-limited effects.ConclusionIn axSpA, patient-reported disease activity and functional capacity are key determinants of mental health, HRQoL, and fatigue. Early diagnosis and initiation of guideline-concordant therapy are associated with improvements across physical and psychological domains, supporting systematic screening and interdisciplinary management strategies.

Objectives To determine the frequency and baseline characteristic differences of complex-to-manage (C2M), difficult-to-manage (D2M) and treatment-refractory (TR) psoriatic arthritis (PsA) in a real-world longitudinal cohort, using the recently proposed 2025 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European Alliance of Associations for Rheumatology (EULAR) definitions. Methods We analysed data from newly diagnosed, disease-modifying antirheumatic drug-naïve patients with PsA enrolled in the Dutch Southwest Early Psoriatic Arthritis cohort between 2013 and 2023. Patients were classified using the 2025 GRAPPA (C2M, TR) and EULAR (D2M, TR) PsA definitions. Frequencies were calculated for each definition. Time-to-event analyses using Kaplan-Meier methods assessed the timing of definition fulfilment and individual components. Longitudinal differences in patient-reported outcomes (PROs) were assessed using linear mixed-effects models. Results Among 885 newly diagnosed patients with PsA, 20% (179/885) fulfilled the GRAPPA-C2M definition, 4.2% (37/885) fulfilled the EULAR-D2M definition, 3.8% (34/885) met the EULAR-TR and 1.2% (11/885) fulfilled the GRAPPA-TR criteria definition during follow-up. Female sex, higher body mass index (BMI), longer symptom duration, presence of enthesitis and greater skin involvement differed with meeting definitions at baseline. Patients classified as GRAPPA-C2M, GRAPPA-TR, EULAR-D2M and EULAR-TR consistently reported worse long-term PROs (Health Assessment Questionnaire-Disability Index scores in C2M (β=0.17, 95% CI 0.10 to 0.24), GRAPPA-TR (β=0.37, 95% CI 0.22 to 0.51), EULAR-D2M (β=0.36, 95% CI 0.20 to 0.48) and EULAR-TR (β=0.40, 95% CI 0.25 to 0.55)). Conclusions Approximately 20% of patients with early PsA fulfilled the GRAPPA-C2M criteria, representing the earliest and broadest subgroup, while 4% met EULAR-D2M/EULAR-TR and 1.2% GRAPPA-TR definitions. These latter subgroups were more likely to be female, had higher BMI, greater skin involvement and enthesitis and experienced persistently worse PROs, underscoring the need for tailored management strategies.

Objectives The Axial Involvement in Psoriatic Arthritis (AXIS) cohort aimed at evaluating the frequency of and clinical and imaging features of axial involvement in psoriatic arthritis (PsA). Methods AXIS (NCT04434885) is a prospective, multicentre, cross-sectional study conducted in 19 countries, by the Assessment of SpondyloArthritis International Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Participants with a diagnosis of PsA meeting ClASsification criteria for Psoriatic ARthritis with musculoskeletal symptom duration ≤10 years and no prior exposure to biological or targeted synthetic disease-modifying antirheumatic drugs were consecutively included. Standardised clinical, laboratory, and imaging assessments (radiography and magnetic resonance imaging of the axial skeleton, including sacroiliac joints [SIJs] and spine), were performed. Imaging was reviewed locally and centrally to detect axial involvement. The presence of axial involvement was determined by local investigator judgement before and after central-imaging review. Results Among 409 participants, axial involvement was identified in 153 (37.4%) based on the investigator’s initial assessment and was decreased to 112 (27.4%) in the final evaluation after incorporating central-imaging review. Participants with axial involvement were younger (45.2 ± 13.8 vs 47.6 ± 12.6 years), more often male (56.3% vs 51.5%), and had a higher frequency of human leukocyte antigen (HLA)-B*27 positivity (22.4% vs 10.8%), inflammatory back pain (IBP) (74.7% vs 43.4%), and elevated C-reactive protein (CRP) (52.7% vs 37.4%). Active inflammatory and structural imaging changes were highly discriminative between participants with and without axial involvement. The central review identified imaging signs of axial involvement (active inflammation or structural lesions) in 95 participants (23.2%). Conclusions Axial involvement was identified in 27.4% of participants with PsA after final diagnostic assessment, with associated features including HLA-B*27 positivity, IBP, elevated CRP, and imaging changes in SIJ or spine.

PURPOSE:To analyze the tear fluid proteome of non-infectious acute anterior uveitis to identify objective markers of inflammation and further dissect the underlying disease pathology. METHODS:Patients from the Uveitis arm of the German Spondyloarthritis Inception cohort with available tear fluid samples and consecutive patients attending the Ophthalmology Department were included. In total, 47 patients with unilateral, non-infectious acute anterior uveitis, including 23 with follow-up samples during non-inflamed state, and 23 healthy controls were enrolled. Tear fluid was collected using Schirmer strips from both eyes during unilateral inflammation and ≥5 months after uveitis resolution from the initially inflamed eye, and from the left eye of healthy individuals. Proteomic analysis was performed by mass spectrometry in data-independent acquisition mode. RESULTS:A total of 1,994 proteins were consistently identified in the tear fluid. Of these, 24 proteins were significantly differently expressed in the eye with active uveitis compared to the non-inflamed fellow eye: the most strongly upregulated proteins were protein S100-P, villin-like protein, and glutamine synthetase, while the most downregulated proteins were protein S100-A7, immunoglobulin kappa joining 3, and prostaglandin D2 synthase. The latter was also downregulated in active uveitis compared to follow-up and healthy controls. Compared to the post-inflammatory samples, active uveitis showed 201 differentially expressed proteins, including upregulation of proteins related to unfolded protein binding and downregulation of proteins involved in metabolic processes and energy-related pathways. CONCLUSION:Uveitis alters the tear fluid proteome, indicating the potential of identifying biomarkers useful for diagnostics and monitoring the course of inflammation.

OBJECTIVES:Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, has demonstrated tolerability and clinical efficacy in patients with PsA. Here, we report an additional year of safety and efficacy of bimekizumab treatment to 3 years. METHODS:BE OPTIMAL [NCT03895203; biologic DMARD (bDMARD)-naïve] and BE COMPLETE [NCT03896581; prior inadequate response/intolerance to TNF inhibitors (TNFi-IR)] assessed s.c. bimekizumab 160 mg every 4 weeks in patients with PsA. Study completers could enrol in the BE VITAL open-label extension (NCT04009499). Outcomes were reported as observed, or using modified non-responder or multiple imputation, to 3 years. RESULTS:Overall, 546/299 (76.7/74.8%) bDMARD-naïve/TNFi-IR patients randomized to bimekizumab or placebo at baseline (Bimekizumab Total group) completed year 3. Treatment-emergent adverse event rates [exposure-adjusted incidence rate/100 patient-years (95% CI)] for bimekizumab-treated patients through 3 years were 164.2 (152.7-176.3) in bDMARD-naïve and 88.6 (79.1-98.9) in TNFi-IR patients, consistent with those at year 1 with no new safety signals identified. Response rates for efficacy outcomes were sustained up to 3 years; at year 1 and year 3, respectively, 56.1/50.4% and 53.2/55.2% of bDMARD-naïve/TNFi-IR patients achieved ACR50, 61.8/58.2% and 59.5/59.1% achieved swollen joint count resolution, and 64.7/66.2% and 61.9/67.5% had 100% improvement from baseline in Psoriasis Area and Severity Index. Responses for other efficacy measures were similarly sustained and consistent in bDMARD-naïve and TNFi-IR patients. CONCLUSION:Bimekizumab demonstrated sustained high levels of efficacy and tolerability to 3 years, supporting its suitability for long-term treatment in bDMARD-naïve and TNFi-IR patients with PsA. TRIAL REGISTRATION:BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499.