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Objective: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone., Methods: Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability (κ) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement (κ) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models., Results: In exercises I, II, and III, mNY κ were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant κ increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not (κ = 0.00, 95% CI -0.10 to 0.10; P = 0.99)., Conclusion: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation's types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan-Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan-Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients' occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes. Key Points • This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients. • The treatment response among of PsA patients seems unaffected by the patients' occupation type., (© 2024. The Author(s).)

Enantiospecific effects play an uprising role in chemistry and technical applications. Chiral molecular networks formed by self-assembly processes at surfaces can be imaged by scanning probe microscopy (SPM). Low contrast and high noise in the topography map often interfere with the automatic image analysis using classical methods. The long SPM image acquisition times restrain Artificial Intelligence-based methods requiring large training sets, leaving only tedious manual work, inducing human-dependent errors and biased labeling. By generating realistic looking synthetic images, the acquisition of real datasets is avoided. Two state-of-the-art object detection architectures are trained to localize and classify chiral unit-cells in a regular molecular chiral network formed by self-assembly of linear molecular bricks. The comparison of different architectures and datasets demonstrates that the training on purely synthetic data outperforms models trained using augmented datasets. A Faster R-CNN model trained solely on synthetic data achieved an excellent mean average precision of 99% on real data. Hence this approach and the transfer to real data show high success, also highlighting the high robustness against experimental noise and different zoom levels across the full experimentally reasonable parameter range. The generalizability of this idea is demonstrated by achieving equally high performance on a different structure, too., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Ferroptosis is a form of iron-dependent regulated cell death caused by the accumulation of lipid peroxides. In this review, we summarize research on the impact of ferroptosis on disease models and isolated cells in various types of arthritis. While most studies have focused on rheumatoid arthritis (RA) and osteoarthritis (OA), there is limited research on spondylarthritis and crystal arthropathies. The effects of inducing or inhibiting ferroptosis on the disease strongly depend on the studied cell type. In the search for new therapeutic targets, inhibiting ferroptosis in chondrocytes might have promising effects for any type of arthritis. On the other hand, ferroptosis induction may also lead to a desired decrease of synovial fibroblasts in RA. Thus, ferroptosis research must consider the cell-type-specific effects on arthritis. Further investigation is needed to clarify these complexities.

Background: Central venous catheters (CVCs) provide an immediate hemodialysis access but are considered to be of elevated risk for complications. It remains unclear, if CVCs per se have relevant impact on clinical outcome. We provide an assessment of CVC-associated complications and their impact on mortality., Methods: In a single center retrospective study, CVC patients between JAN2015-JUN2021 were included. Data on duration of CVC use, complications and comorbidities was collected. Estimated 6-month mortality was compared to actual death rate., Results: About 478 CVCs were analyzed. Initiation of dialysis was the main reason for CVC implantation. Death was predominant for termination of CVC use. Infections were rare (0.6/1000 catheter days), complications were associated with certain comorbidities. Actual 6-month mortality was lower than predicted (14.3% vs 19.6%)., Conclusion: (1) CVCs are predominantly implanted for initiation of hemodialysis; (2) serious complications are rare; (3) complications are associated with certain comorbidities; and (4) CVC patients survive longer than predicted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment., Methods: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively)., Results: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi., Conclusion: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available., Methods: Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors., Results: Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively., Conclusion: In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy-chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging, and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale., Method: Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or non-fatal stroke, or myocardial infarction (MI), while elective coronary revascularization (ECR) was the secondary endpoint. Discriminant accuracy and incidence rate ratios (IRR) were respectively assessed using C-statistics and Poisson regression models., Results: During follow-up, 2.4% (35/1,472) of patients had a MACE, consisting of 6 CV deaths, 11 MIs, and 18 strokes; ECR occurred in 2.1% (31/1,472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE [C-statistics: 0.60, 95% confidence interval (95% CI): 0.57-0.98, p  = 0.03], mostly driven by CV deaths (C-statistics: 0.77; 95% CI: 0.57-0.98, p  = 0.01). IRR indicated that each unit of AAA1 IgG increase was associated with a fivefold incident CV death rate, independent of models' adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for MACE. AAA1 inversely correlated with total and HDL cholesterol., Conclusions: AAA1 independently predicts CV deaths, and marginally MACE in RA. Further investigations are requested to ascertain whether AAA1 could enhance CV risk stratification by identifying patients with RA at low CV risk., Competing Interests: AF and DD have received consultancies from AbbVie, AstraZeneca, BMS, Lilly, Pfizer, and UCB; and research support to their institution from AbbVie, BMS, Galapagos, Lilly, and Pfizer. NV declared to be president of the FAMH (Association of Medical Laboratories of Switzerland) and past president of the Swiss Society of Clinical Chemistry. No other relationships or activities appear to have influenced the submitted work. NV and SP are named as co-inventors of the patent related to cterA1, peptide (“Mimetic peptides for prognosis, diagnosis or treatment of a cardiovascular disease”, No. P1347EP00). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Mongin, Pagano, Lamacchia, Juillard, Antinori-Malaspina, Dan, Ciurea, Möller, Gabay, Finckh and Vuilleumier.)

Objective: A lack of representation in pivotal trials currently limits guidance for the use of biologic DMARDs (bDMARDs) in PsA patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with a low vs high number of affected joints., Methods: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or <3 swollen joints or high joint count (HJC) patients with ≥3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models., Results: A total of 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health-related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC patients were less often on conventional synthetic DMARDs (csDMARDs). Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC patients in both crude and adjusted analyses [hazard ratio (HR) 1.09 (95% CI 0.76, 1.58), P = 0.52]. Furthermore, bDMARD retention was significantly better [HR 0.63 (95% CI 0.47, 0.85), P < 0.002] when administered with csDMARD co-therapy., Conclusions: bDMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset., Methods: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment., Results: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years., Conclusion: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi., Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator., Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively)., Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD)., Methods: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders., Results: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96])., Conclusion: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi., (© 2024. The Author(s).)

Objectives: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries., Methods: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors., Results: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99)., Conclusion: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting mainly the axial skeleton. Peripheral involvement (arthritis, enthesitis and dactylitis) and extra-musculoskeletal manifestations, including uveitis, psoriasis and bowel inflammation, occur in a relevant proportion of patients. AS is responsible for chronic and severe back pain caused by local inflammation that can lead to osteoproliferation and ultimately spinal fusion. The association of AS with the human leucocyte antigen - B27 gene, together with elevated levels of chemokines, CCL17 and CCL22, in the sera of patients with AS, led us to study the role of CCR4 + T cells in the disease pathogenesis., Methods: CD8 + CCR4 + T cells isolated from the blood of patients with AS (n=76) or healthy donors were analysed by multiparameter flow cytometry, and gene expression was evaluated by RNA sequencing. Patients with AS were stratified according to the therapeutic regimen and current disease score., Results: CD8 + CCR4 + T cells display a distinct effector phenotype and upregulate the inflammatory chemokine receptors CCR1, CCR5, CX3CR1 and L-selectin CD62L, indicating an altered migration ability. CD8 + CCR4 + T cells expressing CX3CR1 present an enhanced cytotoxic profile, expressing both perforin and granzyme B. RNA-sequencing pathway analysis revealed that CD8 + CCR4 + T cells from patients with active disease significantly upregulate genes promoting osteogenesis, a core process in AS pathogenesis., Conclusions: Our results shed light on a new molecular mechanism by which T cells may selectively migrate to inflammatory loci, promote new bone formation and contribute to the pathological ossification process observed in AS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods., Methods: The SPARCC-SIJ RETIC e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility., Results: The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores., Conclusion: The SPARCC-SIJ RETIC e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria., Competing Interests: Competing interests: WM has received honoraria/consulting fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma; research grants from AbbVie, Pfizer and UCB Pharma; and educational grants from AbbVie, Janssen, Novartis and Pfizer. WM is the Chief Medical Officer for CARE ARTHRITIS. MØ has received research grants from AbbVie, BMS, Merck, Novartis and UCB and speaker and/or consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. RM received honoraria for lectures or presentations from AbbVie, Eli Lilly, Janssen, Gilead and Pfizer. BM received travel expenditures, honoraria for lectures or presentations from AbbVie, Janssen, Novartis and Pfizer. MJN has received honoraria for travel expenditures, lectures or presentations from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB. MdH received honoraria for presentations from UCB. RM received honoraria for presentations from UCB., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To characterise the population fulfilling the Assessment of SpondyloArthritis international Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) and to determine the effectiveness of a first tumour necrosis factor inhibitor (TNFi) in early versus established axSpA in a large observational registry., Methods: A total of 3064 patients with axSpA in the Swiss Clinical Quality Management registry with data on duration of axial symptoms were included (≤2 years=early axSpA, N=658; >2 years=established axSpA, N=2406). Drug retention was analysed in patients starting a first TNFi in early axSpA (N=250) versus established axSpA (N=874) with multiple-adjusted Cox proportional hazards models. Adjusted logistic regression analyses were used to determine the achievement of the ASAS criteria for 40% improvement (ASAS40) at 1 year., Results: Sex distribution, disease activity, impairments of function and health-related quality of life were comparable between patients with early and established axSpA. Patients with established disease were older, had more prevalent axial radiographical damage and had a higher impairment of mobility. A comparable TNFi retention was found in early versus established disease after adjustment for age, sex, human leucocyte antigen-B27 status, education, body mass index, smoking, elevated C reactive protein and sacroiliac inflammation on MRI (HR 1.05, 95% CI 0.78 to 1.42). The adjusted ASAS40 response was similar in the two groups (OR 1.09, 95% CI 0.67 to 1.78). Results were confirmed in the population fulfilling the ASAS classification criteria., Conclusion: Considering the recent ASAS definition of early axSpA, TNFi effectiveness seems comparable in early versus established disease., Competing Interests: Competing interests: The SCQM Foundation is supported by the Swiss Society of Rheumatology and by AbbVie, AstraZeneca, Eli Lilly, iQone Healthcare, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Samsung Bioepis and Sandoz. AC received honoraria for lectures from AbbVie and Novartis. AR-R received consulting fees from AbbVie, Janssen and Pfizer; honoraria for lectures from AbbVie, Janssen, Novartis and Pfizer; as well as support for attending meetings from Janssen and Pfizer. AS received consulting fees from Pfizer and support for attending meetings from Gilead. BM received speaking fees from AbbVie, Janssen, Novartis and Pfizer, as well as support for attending meetings from Janssen. DK received a research grant from AbbVie, honoraria for presentations from AbbVie and Eli Lilly, support for attending meetings from Janssen and Eli Lilly, as well as payments for participation in advisory boards from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and Roche. MJN received consulting and/or speaking fees from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, as well as a research grant from Novartis. OD received consulting fees from AbbVie. PE received financial support from UCB to attend a meeting. RM received honoraria for lectures or presentations from AbbVie, Eli Lilly, Janssen, Gilead and Pfizer. TH received royalties from Curmed, payments for lectures and presentations from Pfizer, Fresenius Kabi, AbbVie, Merck Sharp & Dohme, Galapagos, Eli Lilly and Novartis. He participated in advisory boards for DETECTRA and holds stock or stock options of Atreon SA and Vtuls. AG, KB, MA and RB declare they have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS). The aim of the study was to determine whether ultrasound detects more Achilles tendon xanthomas (ATX) than clinical examination., Methods: We recruited 100 consecutive patients with LDL-C ≥4 mmol/l. Achilles tendons were evaluated through clinical examination by trained physicians and sonographic examination by another physician blind to the results of clinical examination. Blind second readings of ultrasound images were performed by an expert in musculoskeletal ultrasound. We compared the proportion of patients with ATX detected by either clinical examination or ultrasound and the proportion of patients with a probable/definite familial hypercholesterolaemia diagnosis on the DLCNS before and after ultrasound., Results: Mean (SD) age was 47 (12) years; mean highest LDL-C was 6.57 mmol/l (2.2). ATX were detected in 23% of patients by clinical examination and in 60% by ultrasound. In consequence, 43% had a probable/definite diagnosis of familial hypercholesterolaemia on the DLCNS using clinical examination compared with 72% when ultrasound was used., Conclusion: Compared to clinical examination, ultrasound examination of the Achilles tendon substantially improves the detection of ATX and may help to better identify patients with familial hypercholesterolaemia who are at high risk for premature cardiovascular disease.

Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients., (© 2023. Springer Nature Limited.)

Objective: As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA)., Methods: AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values., Results: A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years., Conclusion: Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression. Key Points • Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA. • Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression., (© 2023. The Author(s).)

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations., Competing Interests: BM, research grant from Novartis (for the present manuscript, paid to employer), Centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328657); MØ, Funding for the present manuscript from Novartis (paid to institution), The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG, research grants from Abbvie, BMS, Merck, Novartis, UCB, consulting fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, support for attending meetings and/or travel from UCB; MJN, grant from Novartis (payment to institution), consulting fees from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), support for attending meetings and/or travel from Janssen, UCB (payment to institution), participation on a Data Safety Monitoring Board or Advisory Board from Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), scientific member of the SCQM registry and the EuroSpA collaboration (unpaid), ASAS-EULAR taskforce member (unpaid); AC, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Merck-Sharp & Dohme, Novartis; BMö, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Novartis, Pfizer, support for attending meetings and/or travel from Abbvie, Janssen, Novartis, Pfizer; LMØ, research grant from Novartis (for the present manuscript, paid to employer); JZ, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Eli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, support for attending meetings and/or travel from Abbvie, Pfizer, Astra Zeneca, participation on a data safety monitoring board or advisory board from Abbvie, UCB, Sobi; BGli, Research grants from Pfizer, AbbVie, BMS (payments made to institution); AM; payment for work done in relation to research questions for this project from the University of Aberdeen, speakers fees for educational events from Galapagos; KL, Honoraria for lectures from Pfizer, Abbvie, Novartis, Janssen, support for attending meetings from Abbvie, Pfizer; DN, Consulting fees from BMS, Lilly, MSD, Novartis, Pfizer, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, support for attending meetings and/or travel from Pfizer; BGu, consulting fees from Novartis, speaker bureaus from Novartis, Nordic Pharma; FI, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Galapagos, Eli-Lilly, Pfizer, UCB, support for attending meetings and/or travel from Pfizer, UCB; PH, research grant (payments made to employer) from Novartis; TKK, consulting fees from AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Grünenthal, Janssen, Sandoz, participation on a data safety monitoring board or advisory board from Abbvie, grants or contracts from AbbVie, BMS, Galapagos, Novartis, Pfizer, UCB; AMR, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, Novartis, support for attending meetings and/or travel from Amgen, Nordic, Theramex, grants or contracts from Novartis, Pfizer, Amgen, Astra Zeneca, Abbvie, MSD, Lilly, Boehringer Ingelheim; CC, None; ZR, Consulting fees from AbbVie, Janssen, Novartis, MSD and Lek Sandoz, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eli Lilly, Janssen, Abbvie, Pfizer, Boehringer Ingelheim, support for attending meetings and/or travel from Gedeon Richter, Pfizer, SOBI (payments made to employer), participation on data safety monitoring board or advisory board from Abbvie, Pfizer, Astra Zeneca, Janssen, Eli Lilly, Novartis and Boehringer Ingelheim; ICF, consulting fees from Pfizer, Galapagos, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Eli-Lilly, Gilead, Janssen, Novartis, MSD, Pfizer, GSK, support for attending meetings and/or travel from Pfizer, Eli-Lilly; JKW, Research support from Abbvie, Amgen, Eli Lilly, Novartis, Pfizer (unrelated to the present work, payment made to Lund University), speakers bureaus from Abbvie and Amgen (payed to Skåne University Hospital), acting co-chair of the Swedish Society for Rheumatology's working group annually updating Swedish treatment recommendations for axial spondyloarthritis and psoriatic arthritis (unpaid, fiduciary assignment); JV, support for the present manuscript from the Czech Ministry of Health–Conceptual Development of Research Organization 00023728 (Institute of Rheumatology), payment to institution, consulting fees from Eli Lilly, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, support for attending meetings and/or travel from Abbvie (payment to institution), participation on a data safety monitoring board or advisory board from Abbvie, Gilead, Pfizer, UCB, grants or contracts from Abbvie (payment to institution); AGL, Consulting fees from Jansen-Cilag A/S, Lilly Nordics, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis Healthcare A/S, Pfizer, support for attending meetings and/or travel from Pfizer, UCB, participation on a data safety monitoring board or advisory board from Jansen-Cilag A/S, Lilly Nordics, UCB; MH; None; SV, None; AMH, Research grant from MSD, grant for attending meeting from Janssen, Pfizer, support for travel cost from Janssen; GG, None; MS, support for the present manuscript from Lilly and Boehringer-Ingelheim, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Pfizer, Boehringer-Ingelheim, GSK, participation on data safety or advisory board from Janssen-Cilag, support for attending meetings and/or travel from Janssen-Cilag; MvdS, Research support/grant from UCB, Eli Lilly, Novartis, Janssen (payments made to institution, AMR Medical Research BV), consulting fees from Novartis, UCB, Abbvie (payments made to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, UCB, Janssen (payments made to institution), support for attending meetings and/or travel from UCB; EKK, None; MJS, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Lilly, Novartis, Pfizer, support for attending meetings and/or travel from Janssen, Viatris, Medac and receipt of equipment, materials, drugs, medical writing, gifts or other services from Vifor; CM, None; MT, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Amgen, Boehringer, Pfizer, Sanofi-Aventis, Roche, Lek-Sandoz, Janssen, Medis, Novartis, participation on data safety or advisory board from Astra Zeneca, Eli Lilly, Janssen, Boehringer, MSD, Novartis, Roche; FDG, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, payment for expert testimony from Abbvie, Galapagos, Janssen, and support for attending meetings and/or travel from Pfizer, Astra Zeneca; DDG, None; MLH, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz, research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordstar (payment to institution). MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis., (© 2023 The Author(s).)

Objective: Obesity is an important comorbidity in axial spondyloarthritis (axSpA); however, the prevalence of obesity in axSpA compared with the general population and associated socioeconomic factors remain unknown., Methods: This repeated cross-sectional study compared BMI (kg/m 2 ) groups of patients with axSpA to the Swiss population at 3 timepoints (2007, 2012, and 2017). BMI categories were compared by different age, sex, and education categories using the chi-square goodness of fit test. Unpaired, 1-sided t tests were used to compare the BMI in patients with axSpA between the different timepoints., Results: Compared to the general population, patients with axSpA had a higher proportion of overweight and obesity: 18.9% of all patients with axSpA were obese, compared to 11.3% of the Swiss population in 2017. Comparison of BMI groups within sex, age, and education groups consistently showed a trend toward higher rates of overweight and obesity in axSpA. Further, patients with axSpA, especially females, showed a trend of increasing BMI over the studied 10 years. At every time point, overweight and obese patients were significantly more likely to be male, were older, and had higher disease activity than patients with normal weight. Obesity was associated with a deprived socioeconomic status as indicated by a higher proportion of patients with manual labor jobs and lower levels of education., Conclusion: The prevalence of obesity was significantly higher among patients with axSpA compared to the Swiss population, with socially disadvantaged individuals being the most affected. There is an urgent need to initiate prevention strategies for obesity in patients with axSpA.

Objective: To investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA)., Methods: AxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Progression was defined as an increase of ≥2 mSASSS units in 2 years. The relationship between sex and progression was investigated with binomial generalised estimating equation models, considering baseline spinal damage as an intermediate covariate. Additional analyses included adjustments for explanatory variables and multiple imputations for missingness., Results: In a total of 505 axSpA patients (317 men and 188 women), mean±SD radiographic progression over 2 years was 1.0±2.8 years in men and 0.3±1.1 years in women (p<0.001). Male sex was associated with enhanced progression in a small model not including baseline damage (OR 3.41, 95% CI 1.87 to 6.21). Both a direct effect of male sex on spinal progression, and an indirect effect, via enhancement of baseline spinal damage were significant (OR 2.06, 95% CI 1.15 to 3.67 and OR 1.04, 95% CI 1.01 to 1.07, respectively). A significant impact of male sex on spinal radiographic progression was still demonstrated after multiple adjustments for covariates known to potentially affect spinal radiographic progression (OR 1.97, 95% CI 1.04 to 3.71)., Conclusions: Spinal radiographic progression in axSpA is more severe in men than in women, with three times higher odds of progression in male patients and an effect that is mediated in part through an increase in baseline radiographic damage., Competing Interests: Competing interests: The SCQM foundation is supported by the Swiss Society of Rheumatology and by Abbvie, Astra Zeneca, Eli Lilly, iQone Healthcare, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Samsung Bioepis, and Sandoz. AC received honoraria for lectures from AbbVie, and Novartis. AS received consulting fees from Pfizer and support for attending meetings from Gilead. BM received speaking fees from Jansen, Novartis and Pfizer, support for attending meetings from Janssen and Pfizer, and a research grant from Celgene. MdH received grants from FWRO/FRSR and honoraria from UCB for participation in an advisory board. MJN received consulting and/or speaking fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis and Pfizer and a research grant from Novartis. He also received support from attending meetings from Janssen and UCB and participated in advisory boards for Eli Lilly, Janssen, Novartis and Pfizer. 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. XB received consulting fees from Abbvie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. He received payment or honoraria for lectures or presentations from Abbvie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. He participated on advisory boards for Abbvie, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB. He is president of the Assessment of Spondyloarthritis international Society (ASAS) and EULAR president-elect. AG, CE, KB, MA, OD, RB and SK declare they have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum., Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group., Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t -tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without., Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.

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., Competing Interests: 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., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the impact of the human leucocyte antigen (HLA)-B27 on the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA)., Methods: A total of 1109 patients with available HLA-B27 status (831 B27+ patients and 278 B27- patients) fulfilling the Assessment of Spondyloarthritis international Society classification criteria for axSpA from the prospective Swiss Clinical Quality Management Registry initiating a first TNFi were included. Drug retention was investigated with multiple adjusted Cox proportional hazard models with imputation of missing values. Multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year., Results: B27+ and B27- patients differed with regard to age, sex, BASDAI, C-reactive protein (CRP), body mass index, enthesitis, uveitis, and classification status. After adjustment for potential confounders for the relationship between HLA-B27 and drug effectiveness (sex and family history of spondyloarthritis), a higher risk of drug discontinuation was found in B27- patients (HR 1.53, 95% CI 1.27-1.83). This difference decreased after additional adjustment for parameters which may act as mediators (HR 1.30, 95% CI 1.30-1.55). Male sex and elevated C-reactive protein (CRP) levels were consistently associated with longer retention. Comparable results were obtained for BASDAI50 responses., Conclusion: The HLA-B27 genotype is an important predictor of treatment effectiveness. Male sex and CRP seem, however, to better describe variability of response in individual patients. This data may help avoiding potential discrimination of B27- individuals with regard to TNFi initiation. Key Points • HLA-B27 is a predictor of effectiveness of TNF inhibitors in axial spondyloarthritis. • Variability of response in individual patients is better defined by sex and objective markers of disease activity, such as C-reactive protein., (© 2022. The Author(s).)

Objectives: To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine)., Methods: Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years., Results: Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14-0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52-1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24-0.77 and 0.85, 95% CI 0.51-1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12-0.80 versus OR 0.56, 95% CI 0.26-1.24 for the cervical and lumbar spine, respectively)., Conclusion: Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA., (© 2023. The Author(s).)

Background: Among chronic back diseases, axial spondylarthritis (axSpA) is the entity with the largest spectrum of specific anti-inflammatory treatment modalities; however, from a general medical perspective axSpA is only ranked as another etiology of back pain to be considered after spinal cord or cauda equina compression, bone metastases, epidural abscess or osteomyelitis of the vertebrae, radiculopathy or spinal stenosis. Due to its relatively low prevalence and mostly later occurring sequelae, there is a danger that axSpA will be a relatively neglected entity for specialists., Results: This article recapitulates the recommendations of the Assessment of Ankylosing Spondyloarthritis International Society (ASAS). This review addresses the practical aspects of the detailed evaluation of treatment attempts carried out so far with nonsteroidal anti-inflammatory drugs (NSAID) for back pain. Undesired effects on the symptoms of the lower intestinal tract could be of particular interest here. The sex-specific differences in the response to treatment with tumor necrosis factor (TNF) inhibitors in axSpA are mentioned. Further aspects of treatment options with biologics in axSpA are discussed based on a case of maintained remission after a course of interleukin (IL) 17 inhibitors in undifferentiated, HLA-B27 and magnetic resonance imaging (MRI) positive axSpA and long-standing good treatment response to IL-12/23 inhibitor treatment in axial psoriatic arthritis. Furthermore, the literature is discussed with respect to uveitis, carditis and amyloidosis in the context of axSpA., Conclusion: The early diagnosis in the general medical context and the specific consideration of numerous predictive factors play an increasingly more important role in the personalized treatment of axSpA., (© 2022. The Author(s).)

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone., Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments., Methods: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months., Results: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III., Conclusion: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti -B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease., Aims and Methods: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti -BAFF therapy belimumab at the University Hospital in Bern, Switzerland., Results: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time., Conclusions: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Leaf epidermis pavement cells form highly complex shapes with interlocking lobes and necks at their anticlinal walls. The microtubule cytoskeleton plays essential roles in pavement cell morphogenesis, in particular at necks. Vice versa, shape generates stress patterns that regulate microtubule organization. Genetic or pharmacological perturbations that affect pavement cell shape often affect microtubule organization. Pavement cell shape and microtubule organization are therefore closely interconnected. Here, we present commonly used approaches for the quantitative analysis of pavement cell shape characteristics and of microtubule organization. In combination with ablation experiments, these methods can be applied to investigate how different genotypes (or treatments) affect the organization and stress responsiveness of the microtubule cytoskeleton., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations., Methods: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings., Results: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain., Conclusion: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations., (Copyright © 2023 by the Journal of Rheumatology.)

Objectives: JAK Inhibitors (JAKi) are recommended DMARDs for patients with moderate-to-severe RA who failed first-line therapy with methotrexate. There is a lack of data allowing an evidence-based choice of subsequent DMARD therapy for patients who had discontinued JAKi treatment. We aimed to compare the effectiveness of TNF inhibitor (TNFi) therapy vs JAKi vs other mode of action (OMA) biologic DMARD (bDMARD) in RA patients who were previously treated with a JAKi., Methods: RA patients who discontinued JAKi treatment within the Swiss RA registry SCQM were included for this observational prospective cohort study. The primary outcome was drug retention for either TNFi, OMA bDMARD or JAKi. The hazard ratio for treatment discontinuation was calculated adjusting for potential confounders. A descriptive analysis of the reasons for discontinuation was performed., Results: Four hundred treatment courses of JAKi were included, with a subsequent switch to either JAKi, TNFi or OMA bDMARD. The crude overall drug retention was higher in patients switching to another JAKi as compared with TNFi and comparable to OMA. A significant difference of JAKi vs TNFi persisted after adjusting for potential confounders., Conclusion: In a real-world population of RA patients who discontinued treatment with a JAKi, switching to another JAKi resulted in a higher drug retention than switching to a TNFi. A switch to a second JAKi seems an effective therapeutic option., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis., Methods: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start)., Results: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis., Conclusion: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare the likelihood of achieving remission between men and women with rheumatoid arthritis (RA) after starting their first biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD)., Methods: This cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included RA patients starting their first b/tsDMARD (1997-31/04/2018). The odds of achieving remission at ≤12-months, defined by disease activity score 28-joints (DAS28) <2.6, were compared between men and women. Secondary analyses were adjusted for age and seropositivity, and we investigated potential mediators or factors that could explain the main findings., Results: The study included 2839 (76.3%) women and 883 (23.7%) men with RA. Compared to women, men were older at diagnosis and b/tsDMARD start, but had shorter time from diagnosis to b/tsDMARD (3.4 versus 5.0 years, p<0.001), and they had lower DAS28 at b/tsDMARD start. Compared to women, men had 21% increased odds of achieving DAS28-remission, with odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02-1.42. Adjusting for age and seropositivity yielded similar findings (adjusted OR 1.24, 95%CI 1.05-1.46). Analyses of potential mediators suggested that the observed effect may be explained by the shorter disease duration and lower DAS28 at treatment initiation in men versus women., Conclusion: Men started b/tsDMARD earlier than women, particularly regarding disease duration and disease activity (DAS28), and had higher odds of reaching remission. This highlights the importance of early initiation of second line treatments, and suggests to target an earlier stage of disease in women to match the benefits observed in men., Competing Interests: The authors have declared that no competing interests exist.

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients., Competing Interests: KL reports personal fees from Gilead-Galapagos, Pfizer, Viatris, Celltrion, outside of the submitted work. AF has received research support from Abbvie, Eli-Lilly, Galapagos, and Pfizer outside of the submitted work, and consultancies or speaker honoraria for Abbvie, BMS, Eli-Lilly, Gilead, Pfizer, Sanofi, and UCB outside of the submitted work. AR-R reports honoraria for consultation and lectures from Abbvie, Amgen, Pfizer, Gilead, Novartis, Janssen, Eli-Lilly, Sanofi, Roche, UCB, BMS outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Raptis, Berger, Ciurea, Andrey, Polysopoulos, Lescuyer, Maletic, Riek, Scherer, von Loga, Safford, Lauper, Möller, Vuilleumier, Finckh and Rubbert-Roth.)

Background: The GERDA ("Protected e-prescription service for pharmacies") project of the Chamber of Pharmacists (LAK) and Pharmacists Association (LAV) of the federal state of Baden-Wuerttemberg provided the opportunity to prescribe medications within the telemedical portal "docdirekt" that is operated by the Association of Statutory Health Insurance Physicians of Baden-Wuerttemberg. Against this background, the aim of the study was to explore and prioritize barriers and enablers among pharmacists to participate in a medical supply system that includes electronic prescriptions (e-prescriptions). Based on these determinants, recommendations for optimizing the successful implementation of similar care offers were derived., Method: A mixed methods design was chosen to explore and prioritize the determinants. In the first step, determinants for participation in an electronic prescribing system were explored by means of individual interviews of docdirekt tele-physicians, primary care physicians and pharmacists. In a second step, these determinants were prioritized through a quantitative survey of pharmacists., Results: Out of the 523 pharmacists that answered the questionnaire, more than half were willing to participate in an e-prescription system, while 8.5% excluded future participation. A total of 18 determinants for the e-prescription system participation could be explored. The protection of the free pharmacy choice for the patients was identified as the most important determinant, followed by the option of a correction function for e-prescriptions (e. g. to avoid retaxing or medication errors), the integration of the e-prescription into the existing pharmacy IT system and the statutory exclusion of direct contracts with online pharmacies. Time savings and possibly higher remunerations were rated as less relevant., Conclusion: More than half of the pharmacies surveyed stated that they wanted to participate in an e-prescription system. Widespread introduction of e-prescriptions in planned for January 2022. Successful implementation of this move will be facilitated if the identified determinants are taken into consideration by politics, software developers and associations., Competing Interests: Die Autoren geben keinen Interessenkonflikt an. Die Studie wurde finanziell durch die Landesapothekerkammer Baden-Württemberg und das Ministerium für Soziales und Integration Baden-Württemberg unterstützt. Die Studie erfolgte weisungsunabhängig., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: To analyse the effect of tumour necrosis factor inhibitors (TNFi) on sacroiliac joint (SIJ) radiographic progression in axial spondyloarthritis (axSpA)., Methods: Patients with axSpA in the Swiss Clinical Quality Management cohort with up to 12 years of follow-up and radiographic assessments every 2 years were included. SIJs were scored by two readers according to the modified New York criteria blinded to chronology. The relationship between TNFi use before or during a 2-year radiographic interval and SIJ progression was investigated using generalised estimating equation models with adjustment for potential confounding. Progression was defined as worsening of ≥1 grade in ≥1 SIJ and ignoring a change from 0 to 1 over 2 years, if both readers agreed. A third reading of radiographs was integrated in sensitivity analyses., Results: A total of 515 patients with axSpA contributed to data for 894 radiographic intervals (24 progression events). In patients with complete covariate data, prior use of TNFi reduced the odds of progression (OR 0.21, 95% CI 0.07 to 0.65). A comparable effect was found for use of TNFi for ≥1 year within a 2-year radiographic interval (OR 0.21, 95% CI 0.08 to 0.55). The inhibitory impact of TNFi was confirmed if progression was demonstrated in 2/3 readings: OR 0.50, 95% CI 0.28 to 0.89 and OR 0.46, 95% CI 0.27 to 0.78 for TNFi treatment before and for ≥1 year within the interval, respectively., Conclusion: TNFi are associated with deceleration of SIJ radiographic progression in patients with axSpA if treatment is continued for ≥1 year., Competing Interests: Competing interests: AC received honoraria for lectures or presentations from AbbVie, Merck Sharp & Dohme and Novartis. AS received consulting fees from Pfizer and support for attending meetings from Gilead. BM received speaking fees from Jansen, Novartis and Pfizer and support for attending meetings from Janssen and Pfizer. MJN received consulting and/or speaking fees from Abbvie, Eli Lilly, Janssen, Novartis and Pfizer and a research grant from Novartis. OD received consulting fees from Abbvie. 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. KB, MA, RB, and SK declare they have no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Multi-cohort projects in medicine provide an opportunity to investigate scientific questions beyond the boundaries of a single institution and endeavor to increase the sample size for obtaining more reliable results. However, the complications of these kinds of collaborations arise during management, with many administrative hurdles. Hands-on approaches and lessons learned from previous collaborations provide solutions for optimized collaboration models. Here, we use our experience in running PGX-link, a Swiss multi-cohort project, to show the strategy we used to tackle different challenges from project setup to obtaining the relevant permits, including ethics approval. We set PGX-link in an international context because our struggles were similar to those encountered during the SYNCHROS (SYNergies for Cohorts in Health: integrating the ROle of all Stakeholders) project. We provide ad hoc solutions for cohorts, general project management strategies, and suggestions for unified protocols between cohorts that would ease current management hurdles. Project managers are not necessarily familiar with medical projects, and even if they are, they are not aware of the intricacies behind decision-making and consequently, of the time needed to set up multi-cohort collaborations. This paper is meant to be a brief overview of what we experienced with our multi-cohort project and provides the necessary practices for future managers., (©Filippo Franchini, Katharina Kusejko, Catia Marzolini, Christoph Tellenbach, Simona Rossi, Susanne Stampf, Michael Koller, Jivko Stoyanov, Burkhard Möller, Alexander Benedikt Leichtle. Originally published in JMIR Formative Research (https://formative.jmir.org), 29.09.2022.)