Objectives To compare two strategies—a hydrocortisone replacement strategy and a prednisone tapering strategy—for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA). Methods The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double-blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA. The primary outcome was the percentage of patients achieving glucocorticoid discontinuation at 12 months. Other secondary outcomes were proportion of flares, need for additional glucocorticoid use, disease activity, patient-reported outcomes and the results of adrenocorticotropic hormone (ACTH) stimulation tests. Results Of the 102 patients randomised in the trial (mean age 62.4 years, 70.6% females), 53 had hydrocortisone replacement and 49 tapered prednisone. At 12 months, 29 patients (55%) in the hydrocortisone replacement group and 23 patients (47%) in the prednisone tapering group achieved glucocorticoid discontinuation (p=0.4). No difference was observed between groups in the secondary outcomes. No cases of acute adrenal insufficiency were observed; however, 17 patients still had an abnormal ACTH stimulation test at 12 months, with no differences between arms. Conclusion A hydrocortisone replacement strategy was not superior to a prednisone tapering strategy for achieving glucocorticoid discontinuation success in patients with RA in LDA. Trial registration number NCT02997605 .

Adeline Ruyssen-Witrand

Clara Brusq

Maëva Masson

Vanina Bongard

Carine Salliot

Lucile Poiroux

Minh Nguyen

Christian Hubert Roux

Christophe Richez

Alain Saraux

Pascale Vergne-Salle

Jacques Morel

René-Marc Flipo

Muriel Piperno

Jacques-Eric Gottenberg

Hubert Marotte

Martin Soubrier

Laure Gossec

Philippe Dieudé

Slim Lassoued

Laurent Zabraniecki

Guillaume Couture

Jean Frédéric Boyer

Bénédicte Jamard

Yannick Degboe

Arnaud Constantin

Annals of the Rheumatic Diseases

Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo-controlled, double-blind trial

低疾病活动度类风湿关节炎患者糖皮质激素撤药两种策略的比较（STAR）：一项随机、安慰剂对照、双盲试验

Objectives CHRFAM7A is a uniquely human fusion gene that functions as a dominant negative regulator of alpha 7 acetylcholine nicotinic receptor (α7nAChR) in vitro. This study determined the impact of CHRFAM7A on α7nAChR agonist responses, osteoarthritis (OA) severity and pain behaviours and investigated mechanisms. Methods Transgenic CHRFAM7A (TgCHRFAM7A) mice were used to determine the impact of CHRFAM7A on knee OA histology, pain severity in OA and other pain models, response to nAchR agonist and IL-1β. Mouse and human cells were used for mechanistic studies. Results Transgenic (Tg) TgCHRFAM7A mice developed more severe structural damage and increased mechanical allodynia than wild type (WT) mice in the destabilisation of medial meniscus model of OA. This was associated with a decreased suppression of inflammation by α7nAchR agonist. TgCHRFAM7A mice displayed a higher basal sensitivity to pain stimuli and increased pain behaviour in the monoiodoacetate and formalin models. Dorsal root ganglia of TgCHRFAM7A mice showed increased macrophage infiltration and expression of the chemokine fractalkine and also had a compromised antinociceptive response to the α7nAchR agonist nicotine. Both native CHRNA7 and CHRFAM7A subunits were expressed in human joint tissues and the CHRFAM7A/CHRNA7 ratio was increased in OA cartilage. Human chondrocytes with two copies of CHRFAM7A had reduced anti-inflammatory responses to nicotine. Conclusion CHRFAM7A is an aggravating factor for OA-associated inflammation and tissue damage and a novel genetic risk factor and therapeutic target for pain.

Alice Courties

Merissa Olmer

Kevin Myers

Phillip Ordoukhanian

Steven R Head

Padmaja Natarajan

Francis Berenbaum

Jérémie Sellam

Martin K Lotz

Human-specific duplicate CHRFAM7A gene is associated with more severe osteoarthritis and amplifies pain behaviours

To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.

Caroline H Shiboski

Stephen C Shiboski

Raphaèle Seror

Lindsey A Criswell

Marc Labetoulle

Thomas M Lietman

Astrid Rasmussen

Hal Scofield

Claudio Vitali

Simon J Bowman

Xavier Mariette

Ann Rheum Dis

2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome

2016年美国风湿病学会/欧洲抗风湿病联盟原发性干燥综合征分类标准

Objectives Analysing expression patterns of Krüppel-like factor (KLF) transcription factors in normal and osteoarthritis (OA) human cartilage, and determining functions and mechanisms of KLF4 and KLF2 in joint homoeostasis and OA pathogenesis. Methods Experimental approaches included human joint tissues cells, transgenic mice and mouse OA model with viral KLF4 gene delivery to demonstrate therapeutic benefit in structure and pain improvement. Mechanistic studies applied global gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq). Results Several KLF genes were significantly decreased in OA cartilage. Among them, KLF4 and KLF2 were strong inducers of cartilage collagen genes and Proteoglycan-4. Cartilage-specific deletion of Klf2 in mature mice aggravated severity of experimental OA. Transduction of human chondrocytes with Adenovirus (Ad) expressing KLF4 or KLF2 enhanced expression of major cartilage extracellular matrix (ECM) genes and SRY-box transcription factor-9, and suppressed mediators of inflammation and ECM-degrading enzymes. Ad-KLF4 and Ad-KLF2 enhanced similar protective functions in meniscus cells and synoviocytes, and promoted chondrocytic differentiation of human mesenchymal stem cells. Viral KLF4 delivery into mouse knees reduced severity of OA-associated changes in cartilage, meniscus and synovium, and improved pain behaviours. ChIP-seq analysis suggested that KLF4 directly bound cartilage signature genes. Ras-related protein-1 signalling was the most enriched pathway in KLF4-transduced cells, and its signalling axis was involved in upregulating cartilage ECM genes by KLF4 and KLF2. Conclusions KLF4 and KLF2 may be central transcription factors that increase protective and regenerative functions in joint tissue cells, suggesting that KLF gene transfer or molecules upregulating KLFs are therapeutic candidates for OA.

Manabu Kawata

Takeshi Teramura

Philip Ordoukhanian

Aishwarya Sundaresan

Hiroshi Asahara

Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis

Krüppel样因子-4和Krüppel样因子-2是关节组织细胞的重要调节因子，可防止骨关节炎中的组织破坏和炎症

<h3>Objective</h3> To investigate the association between weight or body mass index (BMI) and the development of hand osteoarthritis. <h3>Methods</h3> Systematic review of observational studies. Medical databases were searched up to April 2008. Articles that presented data on the association between weight and hand osteoarthritis were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring system. Using the mean scores of all studies as a cut-off value, the studies were deemed as high or low quality. Study quality and study designs were combined to determine the level of evidence using best-evidence synthesis, which consisted of five levels of evidence. <h3>Results</h3> From the 25 studies included, two had cohort, three case–control and 20 cross-sectional study designs. Fifteen studies were considered high-quality studies. Of these high-quality studies, one cohort, two case–control and seven cross-sectional studies showed a positive association between weight or BMI and hand osteoarthritis. Based on three high-quality studies with preferred study designs (one cohort and two case–control) with a positive association, the level of evidence of the association between overweight and developing hand osteoarthritis is moderate. The approximate risk ratio of this association is 1.9. <h3>Conclusion</h3> Weight or BMI is associated with the development of hand osteoarthritis. The level of evidence of published studies is moderate according to best-evidence synthesis. Further high-quality cohort or case–control studies are needed to elucidate the role of weight in hand osteoarthritis.

E. Yusuf

R. G. Nelissen

A. Ioan-Facsinay

V. Stojanovic-Susulic

J. DeGroot

G. van Osch

S. Middeldorp

T. W. J. Huizinga

M. Kloppenburg

Association between weight or body mass index and hand osteoarthritis: a systematic review

体重或体质指数与手部骨关节炎的关联：一项系统综述

Objectives To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed. Methods We examined whether symptomatic (≥1 joint(s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity. Results We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity. Conclusions Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation.

Ida K Haugen

Vasan S Ramachandran

Devyani Misra

Tuhina Neogi

Jingbo Niu

Tianzhong Yang

Yuqing Zhang

David T Felson

Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study

<h3>Background</h3> There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. <h3>Objective</h3> To systematically review the literature for the relationship between serum CRP levels measured by a high sensitivity method (high sensitive CRP (hs-CRP)) and OA, as well as the correlation between circulating CRP levels and OA phenotypes. <h3>Methods</h3> MEDLINE, EMBASE and CINAHL databases were systematically searched from January 1992 to December 2012. Studies were included when they met the inclusion criteria and data from studies were extracted. Two independent reviewers assessed study quality using a modified Newcastle-Ottawa Quality Assessment Scale. Meta-analyses were performed to pool available data from included studies. <h3>Results</h3> 32 studies met the inclusion criteria. Serum hs-CRP levels in OA were modestly but statistically significantly higher than controls (mean difference=1.19 mg/L, 95% CI 0.64 to 1.73, p&lt;0.001) with significant heterogeneity between studies. Levels were significantly associated with pain (r=0.14, 95% CI 0.09 to 0.20, p&lt;0.001) and decreased physical function (r=0.25, 95% CI 0.13 to 0.39, p&lt;0.001). No significant associations were found between hs-CRP levels and radiographic OA. <h3>Conclusions</h3> Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA.

Xingzhong Jin

Julieta Ruiz Beguerie

Weiya Zhang

Leigh Blizzard

Petr Otahal

Graeme Jones

Changhai Ding

Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis

骨关节炎中的循环C反应蛋白：系统评价和Meta分析

To test the hypothesis that bone scintigraphy will predict the outcome of osteoarthritis (OA) of the knee joint.Ninety four patients (65 women, 29 men; mean age 64.2 years) with established OA of one or both knee joints were examined in 1986, when radiographs and bone scan images (early and late phase) were also obtained. The patients were recalled, re-examined, and had further radiographs taken in 1991. Paired entry and outcome radiographs were read by a single observer, blinded to date order and other data. Scan findings and other entry variables were related to outcome. Progression of OA of the knee was defined as an operation on the knee or a decrease in the tibiofemoral joint space of 2 mm or more.Over the five year study period 10 patients died and nine were lost to follow up. Fifteen had an operation on one or both knees (22 knees). Of the remaining 120 knees (60 patients) analysed radiographically, 14 (12%) had progressed in the manner defined. Of 32 knees with severe scan abnormalities, 28 (88%) showed progression, whereas none of the 55 knees with no scan abnormality at entry progressed. The strong negative predictive power of scintigraphy could not be accounted for by disease severity or any combination of entry variables. Pain severity predicted a subsequent operation, but age, sex, symptom duration, and obesity had no predictive value.Scintigraphy predicts subsequent loss of joint space in patients with established OA of the knee joint. This is the first description of a powerful predictor of change in this disease. The finding suggests that the activity of the subchondral bone may determine loss of cartilage.

P Dieppe

J Cushnaghan

P Young

J Kirwan

Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy.

Objectives How inflammatory signalling contributes to osteoarthritis (OA) susceptibility is undetermined. An allele encoding a hyperactive form of the Receptor Interacting Protein Kinase 2 (RIPK2) proinflammatory signalling intermediate has been associated with familial OA. To test whether altered nucleotide-binding oligomerisation domain (NOD)/RIPK2 pathway activity causes heightened OA susceptibility, we investigated whether variants affecting additional pathway components are associated with familial OA. To determine whether the Ripk2 104Asp disease allele is sufficient to account for the familial phenotype, we determined the effect of the allele on mice. Methods Genomic analysis of 150 independent families with dominant inheritance of OA affecting diverse joints was used to identify coding variants that segregated strictly with occurrence of OA. Genome editing was used to introduce the OA-associated RIPK2 (p.Asn104Asp) allele into the genome of inbred mice. The consequences of the Ripk2 104Asp disease allele on physiology and OA susceptibility in mice were measured by histology, immunohistochemistry, serum cytokine levels and gene expression. Results We identified six novel variants affecting components of the NOD/RIPK2 inflammatory signalling pathway that are associated with familial OA affecting the hand, shoulder or foot. The Ripk2 104Asp allele acts dominantly to alter basal physiology and response to trauma in the mouse knee. Whereas the knees of uninjured Ripk2 Asp104 mice appear normal histologically, the joints exhibit a set of marked gene expression changes reminiscent of overt OA. Although the Ripk2 104Asp mice lack evidence of chronically elevated systemic inflammation, they do exhibit significantly increased susceptibility to post-traumatic OA (PTOA). Conclusions Two types of data support the hypothesis that altered NOD/RIPK2 signalling confers susceptibility to OA.

Michael J Jurynec

Catherine M Gavile

Matthew Honeggar

Ying Ma

Shivakumar R Veerabhadraiah

Kendra A Novak

Kazuyuki Hoshijima

Nikolas H Kazmers

David J Grunwald

NOD/RIPK2 signalling pathway contributes to osteoarthritis susceptibility

NOD/RIPK2信号通路促进骨关节炎易感性

Recurrent abdominal pain accounts for a significant proportion of attenders and high impact users in the emergency department. Due to the heterogeneity of presentation and the broad spectrum of possible causes, abdominal pain presents as a significant clinical challenge within the emergency department, particularly as distress and pain are commonly elevated. Patients in this group are routinely prescribed opiate-based interventions and repeated investigations in a ‘better safe than sorry’ culture which saturates the field of persistent physical symptoms. This approach is contributing to the growing problem, and fuelling a cycle of repeated attendance and failure to resolve. This article reviews the current clinical and psychophysiological understanding of recurrent abdominal pain, critiquing guidelines and approaches to diagnosis and management. We offer an alternative evidence-based biopsychosocial approach using the mnemonic ‘ERROR’, recommending five steps to assessment and clinical management of recurrent abdominal pain in the emergency department.

K D Brandt

Yet more evidence that osteoarthritis is not a cartilage disease

风湿病年鉴 (ARD) 是一份国际同行评审期刊，致力于促进最高标准的科学交流和教育。它涵盖了风湿病学的所有方面，包括肌肉骨骼疾病、关节炎疾病和结缔组织疾病的谱系。 ARD 发表基础、临床和转化科学研究。鼓励简明的科学交流，并以同行评审的国际会议论文集为特色。教育论文包括最先进的评论、“如何”文章和教育案例，重点关注临床实践中面临的问题。该杂志于 1939 年首次出版，拥有权威的全球编辑委员会和不断增长的国际读者群。

The Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal dedicated to promoting the highest standards of scientific communication and education. It covers all aspects of rheumatology, including musculoskeletal disorders, arthritic diseases, and connective tissue diseases. ARD publishes basic, clinical, and translational scientific research, encouraging concise scientific communication and featuring peer-reviewed conference proceedings. Educational papers include cutting-edge reviews, 'how-to' articles, and educational cases, focusing on issues faced in clinical practice. Since its first publication in 1939, the journal has maintained a prestigious global editorial board and a growing international readership.

《Annals of the Rheumatic Diseases》（风湿病年鉴，ARD）是一份国际同行评审的学术期刊，旨在促进高标准的科学交流与教育。期刊涵盖风湿病学的各个方面，包括肌肉骨骼疾病、关节炎和结缔组织疾病等。ARD发表基础研究、临床研究和转化科学研究，鼓励简洁明了的科学交流，并定期刊登国际会议的同行评审论文。教育类论文包括前沿评论、实用指南和教育案例，重点关注临床实践中遇到的问题。该杂志自1939年创刊以来，拥有权威的全球编辑委员会和不断扩大的国际读者群。

Journals	Annals of the Rheumatic Diseases
ISSN	0003-4967, 1468-2060
h-index	288
Journal Impact	20.18
Quartiles(Global)	RHEUMATOLOGY(Q1)
Quartiles(China)	医学(1区)医学风湿病学(1区)