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Objectives Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.Methods Pooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.Results Eight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.Conclusions Unsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.

Objectives To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA).Methods Patients with a clinical diagnosis of axSpA from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort with work-related data and up to 5-year follow-up were studied. Incidence, time to first SL and potential role of baseline and time-varying clinical and socioeconomic factors (age, gender, ethnicity, education, job type, marital and parental status) were analysed. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable time-varying Cox survival model building.Results In total, 704 axSpA patients were included (mean (SD) age 33.8 (8.6); 46% men). At baseline, 80% of patients were employed; of these, 5.7% reported being on SL. The incidence of SL among those at risk during the study period (n=620, 88%) was 0.05 (95% CI 0.03 to 0.06) per 1000 days of follow-up. Mean (SD) time to first SL was 806 (595) days (range: 175–2021 days). In multivariable models, male gender (HR 0.41 (95% CI 0.20 to 0.86)) and higher education (HR 0.48 (95% CI 0.24 to 0.95)) were associated with lower hazard of SL, while higher disease activity (HR 1.49 (95% CI 1.04 to 2.13)), older age, smoking and use of tumour necrosis factor inhibitors were associated with higher hazard of SL.Conclusions In this early axSpA cohort of young, working-age individuals, male gender and higher education were independently associated with a lower hazard of SL, whereas older age and higher disease activity were associated with higher hazard of SL. The findings suggest a role of socioeconomic factors in adverse work outcomes, alongside active disease.

Background: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations.Methods: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach.Results: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended.Conclusions: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease. [ABSTRACT FROM AUTHOR]

Background Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further. Objectives To investigate whether XOIs and colchicine are associated with decreased risk of MI. Methods This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings. Results The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)). Conclusions Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect. [ABSTRACT FROM AUTHOR]

Objectives To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). Methods A multidisciplinary guideline development group of 15 experts, representing 10 European countries, generated key propositions for management of CPPD using a Delphi consensus approach. For each recommendation research evidence was searched systematically. Whenever possible, the effect size and number needed to treat for efficacy and RR or OR for side effects were calculated for individual treatment modalities. Strength of recommendation was assessed by the European League Against Rheumatism visual analogue scale. Results Nine key recommendations were generated, including topics for general management, treatment of acute attacks, prophylaxis against recurrent acute attacks and management of chronic symptoms. It was recommended that optimal treatment requires both non-pharmacological and pharmacological treatments. For acute CPP crystal arthritis, cool packs, temporary rest and joint aspiration combined with steroid injection are often sufficient. For prophylaxis or chronic inflammatory arthritis with CPPD, oral non-steroidal anti-inflammatory drugs with gastroprotective treatment and/or low-dose colchicine 0.5–1.0 mg daily may be used. Other recommendations included parenteral or oral corticosteroid for acute CPP arthritis in those unresponsive or unsuited to other measures, and low-dose corticosteroid, methotrexate or hydroxychloroquine for chronic inflammatory arthritis with CPPD. Asymptomatic CPPD requires no treatment. Strength of recommendations varies from 79% to 95%. Conclusion Nine key recommendations for management of CPP crystal associated arthritis were developed using both research evidence and expert consensus. Strength of recommendations was provided to assist the application of these recommendations. [ABSTRACT FROM PUBLISHER]

Objectives To agree terminology and to develop recommendations for the diagnosis of calcium pyrophosphate deposition (CPPD). Methods The European League Against Rheumatism (EULAR) CPPD Task Force, comprising 15 experts from 10 countries, agreed the terms and recommendations for diagnosis of CPPD using a Delphi consensus approach. Evidence was systematically reviewed and presented in terms of sensitivity, specificity and positive likelihood ratio (LR) to support diagnosis; ORs were used for association. Strength of recommendation (SOR) was assessed by the EULAR visual analogue scale. Results It was agreed that ‘CPPD’ should be the umbrella term that includes acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis (OA) with CPPD and chronic CPP crystal inflammatory arthritis. Chondrocalcinosis (CC) defines cartilage calcification, most commonly due to CPPD and detected by imaging or histological examination. A total of 11 key recommendations were generated on the topics of clinical features, synovial fluid (SF) examination, imaging, comorbidities and risk factors. Definitive diagnosis of CPPD relies on identification of SF CPP crystals. Rapid onset inflammatory symptoms and signs are suggestive but not definitive for acute CPP crystal arthritis. Radiographic CC is not highly sensitive or specific, whereas ultrasonography appears more useful (LR=24.2, 95% CI 3.51 to 168.01) for peripheral joints. Recognised risk factors for CPPD include ageing, OA and metabolic conditions such as primary hyperparathyroidism, haemochromatosis and hypomagnesaemia; familial forms are rare. SORs varied from 53 to 99 (maximum 100). Conclusion New terms for CPPD were agreed and 11 key recommendations for diagnosis of CPPD were developed using research evidence and expert consensus. [ABSTRACT FROM PUBLISHER]

Objectives: To investigate the effects of interleukin 1beta (IL1beta) treatment on the Notch1/Hes1 pathway in chondrocytes in vitro. Methods: Mouse articular chondrocytes in primary culture were challenged with IL1beta, alone or combined with Notch1 and IL1beta pathway inhibitors. Notch1 and Hes1 expressions were investigated by immunocytochemistry, western blot and real-time quantitative (q)PCR. IL1beta-responsive genes were assessed by real-time qPCR and a specific siRNA against Hes1 was used to identify Hes1 target genes. Results: Notch1 labelling remained nuclear and stable in intensity irrespective of treatment, suggesting a steady state activation of this pathway in our model. IL1beta transiently increased Hes1 mRNA (2.5-fold) and protein expression in treated versus naive chondrocytes. Hes1 mRNA level then decreased below control and its cyclic pattern of expression was lost. This was associated with nuclear translocation of the cytoplasmic Hes1 protein. IL1beta induced increase in Hes1 mRNA was transcriptional, occurred through nuclear factor (NF)kappaB activation and appeared to be associated with downregulation by its own protein. Hes1 induction was insensitive to the gamma-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester (DAPT), which suggested its independence from novel Notch1 activation. Hes1 expression was efficiently silenced by a specific siRNA. This experiment revealed that Hes1 did not mediate IL1beta-induced downregulation of Sox9, type II collagen and aggrecan transcription but mediated IL1beta induction of matrix metalloproteinase (MMP)13 and ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). The Hes1-related repressor Hey1 was expressed at a very low level and was not inducible by IL1beta. Conclusion: Hes1 is a novel IL1beta target gene in chondrocytes which influences a discrete subset of genes linked to cartilage matrix remodelling and/or degradation. [ABSTRACT FROM AUTHOR]

Objective: To determine whether 17beta-oestradiol (E2) modulates interleukin (IL) 1beta-induced proteoglycan degradation in chondrocytes, and to analyse the part played by metalloproteinases (MMPs) in this process.Methods: Primary cultured rabbit articular chondrocytes were prepared and treated with 10 ng/ml IL1beta combined or not with 0.1-10 nM E2. Neosynthesised proteoglycans (PGs) were evaluated after incorporation of [(35)SO(4)]sulphate and further analysed after chromatography on a Sepharose 2B column. Chondrocyte mRNA levels of aggrecan, MMP-1, -3, -13, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were studied by northern blot. MMP-1 activity was measured by zymography. MMP-1 gene transcription was studied by transient transfection of chondrocytes with an MMP-1-luciferase construct.Results: E2 modulated the IL1beta-induced total sulphated PGs in rabbit articular chondrocytes, which decreased as the E2 concentration was increased. At a low concentration (0.1 nmol/l) E2 counteracts the IL1beta-induced decrease in sulphated PG, while at high concentration (10 nmol/l) E2 enhances the IL1beta effects. A biphasic E2 effect was also observed on IL1beta-induced disaggregation of PG, 53-58 kDa gelatinolytic activity, and MMP-1, -3, and -13 mRNA levels. In contrast, E2 did not modify the level of aggrecan mRNA and had no effect on TIMP-1 mRNA expression. Finally, simultaneous addition of IL1beta and E2 (0.1-10 nmol/l) did not modify IL1beta-induced MMP-1-luciferase activity, suggesting that E2 effects probably occur at the post-transcriptional level of MMP gene expression.Conclusion: Oestrogen concentration may have an inverse effect on IL1beta stimulated proteoglycan degradation and MMP production by chondrocytes. [ABSTRACT FROM AUTHOR]

Objectives: Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients' overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials., Methods: Pooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated., Results: Eight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks., Conclusions: Unsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions., Competing Interests: Competing interests: PR has received fees from AbbVie, Amgen, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer and UCB. MV has received research grants, consulting or speaker fees from AbbVie, Amgen, the Dutch Arthritis Foundation, Eli Lilly, Janssen, Novartis, Pfizer and UCB. SO has received fees from AbbVie, BMS, Janssen, Mylan, Novartis and Pfizer. WT has received research grants, consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer and UCB. JR has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB. MN is a former employee of Janssen and is now an employee of Takeda Pharmaceuticals International AG. ET is a former employee of Janssen. MZ, MvS, WN and MS are employees of Janssen and own stock in Johnson & Johnson. AK is an employee of Janssen Global Services, R&D, and owns stock in Johnson & Johnson. AZ has received research grants from Novartis, and speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB., (© 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.)

Objectives: Patient care can vary substantially by country. The objective was to explore differences in psoriatic arthritis (PsA) across countries for disease activity, impact and treatments., Methods: A cross-sectional analysis of 13 countries from the Remission/Flare in PsA study (NCT03119805) of consecutive adult patients with definite PsA was performed. Countries were classified into tertiles by gross domestic product (GDP)/capita. Disease activity (Disease Activity in PsA, DAPSA and Minimal Disease Activity, MDA) and their components, disease impact (patient-reported outcomes) and biological disease-modifying antirheumatic drugs (bDMARDs) were analysed per country and compared between the three tertiles of GDP/capita by parametric and non-parametric tests. We also explored the percentage of patients with significant disease activity (DAPSA >14) and no ongoing bDMARD prescription., Results: In 439 patients (50.6% male, mean age 52.3 years, mean disease duration 10.1 years), disease activity and disease impact were higher in the lowest GDP/capita countries. DAPSA remission and MDA were attained in the lowest tertile in 7.0% and 18.4% patients, vs 29.1% and 49.5% in the middle tertile and 16.8% and 41.3% in the high tertile, respectively (all p<0.001). bDMARDs use was similar in the tertiles (overall mean 61%). The overall rate of patients with DAPSA >14 and no bDMARDs was 18.5%, and was higher in lower GDP/capita countries (p=0.004)., Conclusion: PsA patients from countries with the lowest GDP/capita, despite similar use of bDMARDs, were more likely to have high disease activity and worse disease impact. There is a need for more equity in healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The consequences of psoriasis associated to axial spondyloarthritis (axSpA) are unclear. The objectives were to determine the prevalence and the consequences of psoriasis in recent axSpA over 6 years of follow-up., Methods: The multicentric prospective cohort DESIR (NCT01648907) of adult patients with recent inflammatory back pain suggestive of axSpA was analysed over 6 years. Psoriasis was recorded at each visit and cumulative prevalence and incidence were calculated. Patients with vs without psoriasis at any time point were compared. Outcomes included disease activity (Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), joint and enthesitis count, CRP), patient-reported outcomes for function (Health Assessment Questionnaire for axSpA, HAQ-AS) and quality of life, and treatment use over 6 years. Outcomes were compared through univariable and multivariable analyses, as well as linear mixed effect models., Results: In 589 patients, mean age 40.5±8.7 years, 45.8% men and baseline mean symptom duration 1.5±0.9 years, the cumulative prevalence of psoriasis increased from 16.8% (99/589) at baseline to 26.8% (158/589) at 6 years, leading to an incidence of 2.1/100 patient-years. Over 6 years of follow-up, patients with psoriasis developed more synovitis (p=0.008), and received more methotrexate (cumulative use, 25.5% vs 11.8%, p<0.001) and biological disease-modifying drugs (55.7% vs 38.5%, p<0.001). There were no significant consequences of psoriasis on other outcomes, including disease activity (ASDAS-CRP), functional capacity (HAQ-AS) and quality of life., Conclusion: Psoriasis is frequent in early axSpA. AxSpA patients with psoriasis had more swollen joints over time and received more biologics; they did not have worse outcomes related to axSpA in terms of activity and severity., Trial Registration Number: NCT01648907., Competing Interests: Competing interests: PR: personal fees from Amgen, Galapagos, Lilly, Pfizer, Sanofi; Abbvie, BMS, Galapagos, Janssen, Novartis, UCB, outside the submitted work. DW: personal fees from AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Celgene, Lilly, Sandoz, Grünenthal, Galapagos, outside the submitted work. BF: grants from AbbVie, Lilly, MSD, Pfizer; personal fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, outside the submitted work. LG: grants from Amgen, Galapagos, Lilly, Pfizer, Sandoz, Sanofi; personal fees from AbbVie, Amgen, BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA)., Methods: Patients with a clinical diagnosis of axSpA from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort with work-related data and up to 5-year follow-up were studied. Incidence, time to first SL and potential role of baseline and time-varying clinical and socioeconomic factors (age, gender, ethnicity, education, job type, marital and parental status) were analysed. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable time-varying Cox survival model building., Results: In total, 704 axSpA patients were included (mean (SD) age 33.8 (8.6); 46% men). At baseline, 80% of patients were employed; of these, 5.7% reported being on SL. The incidence of SL among those at risk during the study period (n=620, 88%) was 0.05 (95% CI 0.03 to 0.06) per 1000 days of follow-up. Mean (SD) time to first SL was 806 (595) days (range: 175-2021 days). In multivariable models, male gender (HR 0.41 (95% CI 0.20 to 0.86)) and higher education (HR 0.48 (95% CI 0.24 to 0.95)) were associated with lower hazard of SL, while higher disease activity (HR 1.49 (95% CI 1.04 to 2.13)), older age, smoking and use of tumour necrosis factor inhibitors were associated with higher hazard of SL., Conclusions: In this early axSpA cohort of young, working-age individuals, male gender and higher education were independently associated with a lower hazard of SL, whereas older age and higher disease activity were associated with higher hazard of SL. The findings suggest a role of socioeconomic factors in adverse work outcomes, alongside active disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout., Methods: Prospective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs., Results: Of 1193 patients, 92% were men with a mean age of 60 years, 6.8 years' disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45)., Conclusions: Failure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival., Competing Interests: Competing interests: FPR: grants from Ministerio de Sanidad, Gobierno de España, Fundación Española de Reumatología and Asociación de Reumatólogos del Hospital de Cruces; consultancies for Menarini, Grünenthal, Horizon, Syneos and Dyve; speakers' bureau for Menarini, Astella, Grünenthal, Logarithm and Fundación Española de Reumatología. PR: fees from Ipsen, Menarini, Grünenthal and Savient. AGS: grants from the Irish Heart Foundation, Midwest Kidney Disease Research and Education Foundation, Limerick and the Health Research Institute, University of Limerick; advisory fees from AstraZeneca, Grünenthal and Menarini; unrestricted grant from the Menarini Foundation. RK: employee of Grunenthal GmbH, Aachen, Germany. MJGdY and LC work for an institution that receives payment for research services from companies interested in gout, concretely, Grünenthal and Novartis. A brother and the mother of LC have gout., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/purpose: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling., Methods: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data., Results: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most., Conclusions: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA., Trial Registration Number: NCT01315652., Competing Interests: Competing interests: None declared.

Objective: To evaluate the prevalence and performance as axial Spondyloarthritis (axSpA) diagnostic feature of radiographic and MRI lesions 'typical' of axSpA of the sacroiliac joint (SIJ) and spine in a mechanical chronic back pain (CBP) population and in an axSpA cohort., Methods: Cross-sectional multicentre study. Patients: (1) recent onset axSpA (DESIR cohort) and (2) mechanical non-axSpA CBP matched for age and gender (ILOS study). Imaging: radiographs and MR scans were performed identically in both groups. All images were centrally read, blinded for diagnosis and for other imaging findings in the same patient. Statistical analysis: prevalence of lesions 'typical of axSpA' were compared in both groups. Sensitivity, specificity and positive likelihood ratios (LR+) of each lesion (and combination of lesions) were calculated., Results: A total of 98 patients with CBP were included, and compared with 100 patients with recent onset axSpA. SIJ lesions were consistently more frequent in the axSpA group (35.0% vs 11.8% p<0.001, 35.0% vs 8.4% p<0.001% and 32.0% vs 10.0%. p<0.001 for modified New York criteria, MRI sacroiliitis and ≥3 erosions of the SIJ on MRI, respectively), and performed well (LR+ for ≥3 erosions 3.0 (95% CI 1.6 to 5.8)). Spine lesions were comparable across groups: radiographic lesions were rare, while all MRI lesions were frequent., Conclusion: Our study confirms that 'typical' lesions can also be observed in patients with non-axSpA CBP but that SIJ lesions by all modalities remain the most valuable for diagnosis, including structural lesions of the SIJ. This suggests the potential interest of adding MRI SIJ structural lesions in the definition of MRI abnormalities for axSpA classification., Competing Interests: Competing interests: AM received an ASAS (Assessment of SpondyloArthritis International Society) research grant and an unrestricted grant from Pfizer (Passerelle) to conduct this study. There are no other benefits from commercial sources for the work reported on in the manuscript, and no other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.

Objectives: To value health resource utilisation and productivity losses in DESIR, a longitudinal French cohort of 708 patients with early spondyloarthritis (SpA) enrolled between 2007 and 2010, and identify factors associated with costs in the first 3 years of follow-up., Methods: Self-reported clinical data from DESIR and French public data were used to value health resource utilisation and productivity losses in 2013 Euros. Factors associated with costs, including and excluding biological drugs, were identified in generalised linear models using the generalised estimating equations algorithm to account for repeated observations over participants., Results: The mean (±SD) annual cost per patient was €5004±6870 in year 1, decreasing to €4961±7457 in year 3. Patients who never received a biologic had mean 3-year total costs of €4789±6022 compared to €38 206±19 829 among those who received a biologic. Factors associated with increased total costs were peripheral arthritis (rate ratio (RR) 1.19; 95% CI 1.04 to 1.37; p<0.0001), time on biologics (RR 1.23 per month; 1.21, 1.24; p<0.0001), and average BASFI score (RR 1.18/10 point increase; 1.15, 1.25; p<0.0001). Factors associated with increased costs excluding biologics were baseline age (RR 1.10 per 5 year increase; 1.05, 1.16; p<0.0001), peripheral arthritis (RR 1.20; 1.02, 1.40; p<0.0133), time on biologics (RR 1.04 per month; 1.02, 1.05; p<0.0001), and average BASDAI score (RR 1.21 per 10 point increase; 1.16, 1.25; p<0.0001)., Conclusions: In addition to biologics, factors like age, peripheral arthritis and disease activity independently increase SpA-related costs. This study may serve as a benchmark for cost of illness among patients with early SpA in the biologic era.

Background: The effectiveness of intra-articular hyaluronic acid (IAHA) injection for knee osteoarthritis (KOA) is debated., Objectives: To evaluate the effect of IAHA for patients with KOA by analysing data from trials of IAHA versus placebo with low risk of bias, to provide the highest level of evidence., Methods: A systematic review and meta-analysis was conducted. Randomised controlled trials (RCTs) with a low risk of bias (adequate randomisation and concealment and double-blind design) that investigated IAHA versus placebo (saline solution) injection were eligible. The primary efficacy measure was pain intensity and secondary outcome function at 3 months. The treatment effect was summarised with the standardised mean difference (SMD) calculated from differences in means of pain and function measures between treatment and control groups at 3 months. Trials were pooled by a random-effects model with DerSimonian and Laird weights. Statistical heterogeneity was explored by a visual exploration of forest plots and the I(2) statistic., Results: A total of eight RCTs (2 199 randomised patients) met our inclusion criteria. IAHA significantly reduced the pain intensity (SMD=-0.21, 95% CI (95% CI) -0.32 to -0.10) and improved function (SMD=-0.12, 95% CI -0.22 to -0.02). Trials showed no heterogeneity., Conclusions: This meta-analysis of high-quality trials of IAHA versus placebo shows that IAHA provides a moderate but real benefit for patients with KOA.