Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

The temporal association between adverse drug reactions and antirheumatic drugs utilisation in Western Australia: a retrospective study from real-world data (1995-2015).

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US). METHODS: Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2). RESULTS: A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period. CONCLUSIONS: The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.

Population-wide long-term study of incidence, renal failure, and mortality rates for lupus nephritis.

OBJECTIVE: Given limited regional data, we investigate the state-wide epidemiology, renal and patient outcomes for lupus nephritis (LN) in Western Australia (WA). METHODS: Patients hospitalized with incident SLE (≥2 diagnostic codes in the state-wide WA Health Hospital Morbidity Data Collection) in the period 1985-2015 were included (n = 1480). LN was defined by the presence of glomerulonephritis and/or raised serum creatinine. Trends over three study decades for annual incidence rate (AIR)/100.000 population, mortality (MR), and end-stage renal disease (ESRD) rates/100 person years were analyzed by least square regression and compared with a matched control group (n = 12 840). RESULTS: Clinical evidence of LN developed in 366 SLE patients (25.9%) after a median disease duration of 10 months (IQR 0-101) with renal biopsy performed in 308 (84.2%). The AIR for LN (0.63/100.000) did not change significantly over time (R2 = .11, p = .85), while point prevalence reached 11.9/100.000 in 2015. ESRD developed in 14.1% (n = 54) of LN patients vs. 0.2% in non-LN SLE patients and 0.05% in controls (all p ≤ 0.01). ESRD rates increased over time in LN patients (0.4 to 0.7, R2 = .52, p = .26). The odds ratio for death was 8.81 (CI 3.78-22.9) for LN and 6.62 (CI 2.76-17.9) for non-LN SLE patients compared to controls and MR for LN patients increased over time (1.3 to 2.2, R2 = .84, p = .26). CONCLUSIONS: The incidence rate of LN in WA remained unchanged over 30 years. A lack of improvement in renal failure and mortality rates illustrates the pressing need for better long-term treatment options and/or strategies in LN.

The longitudinal study of muscle changes with ultrasound: differential changes in idiopathic inflammatory myopathy subgroups.

OBJECTIVES: We investigated shear wave elastography (SWE), B mode US and power Doppler (PDUS) as imaging biomarkers for longitudinal follow-up in idiopathic inflammatory myopathy (IIM), with a particular focus on immune-mediated necrotizing myopathy (IMNM) and DM. METHODS: Participants had serial SWE, PDUS on the deltoid (D) and vastus lateralis (VL) muscles on four occasions at intervals of 3-6 months. Clinical assessments included manual muscle testing, and patient- and physician-reported outcome scales. RESULTS: Thirty-three participants were included: IMNM = 17, DM = 12, overlap myositis = 3, PM = 1. Twenty were in a prevalent clinic group, and 13 were recently treated cases in an incident group. Differential changes in SWS and US domains occurred with time in both the prevalent and incident groups. In the VL-prevalent subgroup, echogenicity increased over time (P = 0.040), while in the incident cases there was a trend for reduction to normal over time (P = 0.097) with treatment. Muscle bulk reduced in the D-prevalent subgroup over time (P = 0.096), suggesting atrophy. SWS also reduced in the VL-incident subgroup over time (P = 0.096), suggesting a trend towards improvement in muscle stiffness with treatment. CONCLUSION: SWE and US appear promising as imaging biomarkers for patient follow-up in IIM and indicate changes over time, especially with echogenicity, muscle bulk and SWS in the VL. Due to the limitations of the participant numbers, additional studies with a larger cohort are needed to help evaluate these US domains further and outline specific characteristics within the IIM subgroups.

A longitudinal study using B mode ultrasound and power Doppler as monitoring imaging tools in inclusion body myositis.

OBJECTIVES: There is growing interest in ultrasound (US) as an outcome measure in IBM. Our study aimed to determine the ability of B mode US and power Doppler (PD) to detect changes in affected muscles over time and if US domains correlate with disease progression. METHODS: Participants attended on four occasions over a median follow-up period of 26 months. All completed a patient self-reported health assessment questionnaire (HAQ), patient visual analogue scale (pVAS), manual muscle testing (MMT), and US (fascial thickness-FT, muscle bulk, echogenicity, and PD) on deltoid and vastus lateralis (VL) muscles at each visit. RESULTS: This longitudinal observational study had 35 participants: 21 (60%) males, median age 70 (IQR (64-76), and the majority (85.7%) not on immunosuppression. When analysed for sex differences at baseline, males had lower FT-VL (p=0.018) and higher muscle bulk (p=0.002) than females. Only FT-deltoid (p<0.001) increased significantly over time with follow-up. When participants were stratified into progressors and non-progressors, FT at baseline was lower in progressors (0.06 vs. 0.09, p=0.017), who were predominantly male. There were no significant differences in other US domains. CONCLUSIONS: Our study highlights previously unreported sex differences in US findings in IBM. Certain US domains, such as FT, showed measurable changes over time and correlated with disease progression. However, further studies with longer follow-up periods and larger patient cohorts will need to be performed to determine whether B mode US could be a useful disease outcome measure for therapeutic trials.

Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. METHODS: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). FINDINGS: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. INTERPRETATION: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. FUNDING: National Health and Medical Research Council of Australia.

Imaging of giant cell arteritis - recent advances.

Imaging is increasingly being used to guide clinical decision-making in patients with giant cell arteritis (GCA). While ultrasound has been rapidly adopted in fast-track clinics worldwide as an alternative to temporal artery biopsy for the diagnosis of cranial disease, whole-body PET/CT is emerging as a potential gold standard test for establishing large vessel involvement. However, many unanswered questions remain about the optimal approach to imaging in GCA. For example, it is uncertain how best to monitor disease activity, given there is frequent discordance between imaging findings and conventional disease activity measures, and imaging changes typically fail to resolve completely with treatment. This chapter addresses the current body of evidence for the use of imaging modalities in GCA across the spectrum of diagnosis, monitoring disease activity, and long-term surveillance for structural changes of aortic dilatation and aneurysm formation and provides suggestions for future research directions.

Mortality Trends Among Patients with Rheumatoid Arthritis in Western Australia.

INTRODUCTION: With scarce comparative data on mortality in Australian patients with rheumatoid arthritis (RA), we investigated temporal changes in standardized mortality rates for patients with RA using longitudinal linked population-wide health data in Western Australia (WA) over the period 1980 to 2015. METHODS: The study included 17,125 patients with a first-time hospital contact for RA (ICD-10-AM M05.00-M06.99 and ICD-9-AM 714.00-714.99) in the study period. Standardized mortality rate ratios (SMRRs) for the RA cohort versus the WA general population was estimated using direct age standardization. We analyzed temporal trends over with dates and causes provided by the WA Death Registry. RESULTS: During 356,069 patient-years of follow-up, a total of 8955 (52%) deaths occurred in the RA cohort. The SMRR was 2.24 (95% CI 2.15-2.34) in males and 3.09 (95% CI 3.00-3.19) in females over the study period. SMRR decreased since 2000 to 1.59 (95% CI 1.39-1.81) for the period 2011-2015. Median survival was 26.80 years (95% CI 26.30-27.30), where age and comorbidity independently increased the risk of death. The leading causes of deaths were cardiovascular diseases (26.60%), cancer (16.80%), rheumatic diseases (5.80%), chronic pulmonary disease 491 (5.50%), dementia (3.00%), and diabetes 235 (2.6%). CONCLUSIONS: The mortality rate in patients with RA in WA has decreased but remains 1.59-times higher than in community counterparts, suggesting that there is room for further improvement. Comorbidity is the main modifiable risk factor to further reduce mortality in patients with RA.

The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. METHODS: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. RESULTS: Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1ß, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. CONCLUSIONS: Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Risk of Major Adverse Cardiovascular Event Following Incident Hospitalization for Acute Gout: A Western Australian Population-Level Linked Data Study.

BACKGROUND: Cardiovascular disease is the most common cause of death in people with gout. Acute inflammation, which is a characteristic of gout, may have a mechanistic role in major adverse cardiovascular events (MACEs). We aimed to examine the relationship between admissions to a hospital with acute gout and MACEs in a large population-based data set. METHODS: We extracted data from the Hospital Morbidity Data Collection and Death Registrations of the Western Australian Rheumatic Disease Epidemiology Registry. We identified patients admitted to hospital with incident acute gout and who had admissions or a death record because of MACEs. We compared the risk of MACEs during the postdischarge period (1-30 days after acute gout admission) and control period (365 days prior to admission and 365 days after the postdischarge period) using a self-controlled case-series (SCCS) design, which is a within-person design that controls for time-invariant patient-specific confounding. We performed conditional fixed-effects Poisson regression to obtain rate ratios (RRs). RESULTS: We identified 941 patients (average age: 76.4 years; SD: 12.6; 66.7% male) with an incident acute gout admission and documented MACEs during the control and/or postdischarge periods. Of the 941 patients, 898 (95%) experienced MACEs during the combined control period (730-day period) and 112 (12%) during the postdischarge period (30-day period). The rates of MACEs during the total control and postdischarge periods were 0.84 and 1.45 events per person-year, respectively. Regression analysis confirmed increased rate during the postdischarge period (RR: 1.67; 95% CI: 1.38-2.03) compared with the control period. Sensitivity analyses indicated that our results were robust in relation to known limitations of the SCCS design. CONCLUSION: We report an increased risk of MACEs in the first 30 days after an incident hospital admission with acute gout, suggesting a temporal association between acute inflammation and subsequent MACEs in patients with gout.

Trends in Hospitalization for Tuberculosis and Other Opportunistic Infections in Australian Patients with Inflammatory Joint Diseases.

OBJECTIVE: As immune-modulating therapy has become the standard of care for idiopathic inflammatory joint diseases (IJD), we investigated whether this has changed the rates for hospitalization with opportunistic infections (OI). METHODS: Administrative longitudinal state-wide health data identified patients hospitalized at least twice with diagnostic codes for rheumatoid arthritis (RA, n = 7730), psoriatic arthritis (PsA, n = 529) or axial spondylarthritis (AS, n = 1126) in Western Australia in the period 1985-2015. Overall incidence rates/1000 person-years (IR with 95% CI) for microbiologically confirmed OI (mycobacterial, fungal, and viral infections) during 180,963 person-years were analyzed across 10-year periods with IR trend rates analyzed by least square regression (R2) for all IJD categories. RESULTS: A total of 2584 OI occurred with higher IR rates observed in RA (15.34, CI 14.71-15.99) than PsA (8.73, CI 7.14-10.56) and AS (10.88, CI 9.63-12.24) patients (p < 0.001). IR rates were highest for Candidiasis across all three IJD categories (IR 10.0 vs. 6.32 vs. 6.88, respectively), while Varicella-zoster (VZV) was most frequent non-candida OI (IR 2.83.0 vs. 1.50 vs. 1.49, respectively) followed by mycobacterial (IR 1.14 vs. 0.08 vs. 0.24, respectively) and other mycotic infections (IR 0.60 vs. 0.58 vs. 0.86, respectively). Over time, the IR for tuberculosis and pneumocystosis decreased and remained stable for VZV infections in RA patients, but IR for all other OI increased across all disease categories. OI admission associated with 6.5% (CI 5.6-7.5) in-hospital mortality. CONCLUSIONS: Despite decreasing admission rates for tuberculosis and pneumocystosis in RA patients, an overall increase in mycotic and viral infection rates over time was seen across all three IJD. Together with a significant case fatality rate, this indicates continued efforts are needed to improve OI prevention in the management of IJD patients.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Reliability and Diagnostic Accuracy of Radiography for the Diagnosis of Calcium Pyrophosphate Deposition: Performance of the Novel Definitions Developed by an International Multidisciplinary Working Group.

OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.

Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.

BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.

Mortality Rates in Patients With Ankylosing Spondylitis With and Without Extraarticular Manifestations and Comorbidities: A Retrospective Cohort Study.

OBJECTIVE: To examine mortality rates in hospitalized patients with ankylosing spondylitis (AS) and the association of extraarticular manifestations (EAMs) and comorbidities with mortality rates. METHODS: This study was a retrospective, population-based cohort study using linked administrative data from patients with AS who were hospitalized (n = 1791) and patients in a matched comparison group (n = 8955). Mortality data for patients were obtained from the Western Australia Death Register. The presence of EAMs and comorbidities was identified from hospital records. Mortality rates were compared between the 2 groups using Cox proportional hazard models overall and stratified by a history of EAMs, comorbidities, and smoking status. RESULTS: Crude mortality rates were significantly higher among patients with AS than among patients in the comparison group (hazard ratio [HR] 1.85, 95% CI 1.62-2.12), with excess mortality in the AS group associated with cardiovascular disease (CVD; HR 5.32, 95% CI 3.84-7.35), cancer (HR 1.68, 95% CI 1.27-2.23), external causes (HR 3.92, 95% CI 2.28-6.77), and infectious diseases (HR 25.92, 95% CI 7.50-89.56). When patients were stratified by history of EAMs, CVD, and smoking, the risk of mortality was elevated in patients both with and without each risk factor. Among patients with AS, histories of CVD (HR 6.33, 95% CI 4.79-8.38), diabetes (HR 2.81, 95% CI 1.99-3.95), smoking (HR 1.49, 95% CI 1.18-1.89), and EAMs (HR 1.62, 95% CI 1.24-2.11) were associated with an increased risk of mortality. CONCLUSION: The presence of comorbidities, EAMs, and smoking contributes to an increased risk of all-cause mortality among patients with AS who are hospitalized compared to patients in the comparison group. These results support the need to prevent or reduce the occurrence of comorbidities and smoking in patients with AS.

Mortality and cause of death in patients with ANCA-associated vasculitis and polyarteritis nodosa in Australia-a population-based study.

OBJECTIVES: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. METHODS: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. RESULTS: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. CONCLUSION: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Development of a new ultrasound scoring system to evaluate glandular inflammation in Sjögren's syndrome: an OMERACT reliability exercise.

OBJECTIVE: The aim of this exercise from the OMERACT Ultrasound subgroup on Sjögren's syndrome was to develop and assess the reliability of a consensus-based semiquantitative colour Doppler US scoring system for pathologic salivary gland vascularization in patients with primary Sjögren's syndrome (pSS). METHODS: Using the Delphi method, a colour Doppler semiquantitative scoring system for vascularization of bilateral parotid and submandibular glands was developed and tested in static images and on patients (9 pSS patients and 9 sonographers). Intra-reader and inter-reader reliability of grading the salivary glands were computed by weighted Cohen and Light's kappa analysis, respectively. RESULTS: The consensus-based semiquantitative score was: grade 0, no visible vascular signals; grade 1, focal, dispersed vascular signals; grade 2, diffuse vascular signals detected in <50% of the gland; grade 3, diffuse vascular signals in >50% of the gland. In static images, the intra- and inter-reader reliability showed excellent kappa values (95% CI) of 0.90 (0.87, 0.93) and 0.80 (0.74, 0.84), respectively, for all four salivary glands together. In patients, the intra- and inter-reader reliability for all four salivary glands together was kappa = 0.84 (0.73, 0.92) and 0.70 (0.64, 0.76), respectively. CONCLUSION: The consensus-based colour Doppler US scoring for the evaluation of salivary gland vascularization in pSS showed a good inter-reader reliability and excellent intra-reader reliability in static images and in patients. The clinical application of the developed scoring system should be tested in clinical settings.

Assessment of liver fibrosis markers in people with rheumatoid arthritis on methotrexate.

BACKGROUND: Up to 3% of methotrexate (MTX)-treated rheumatoid arthritis (RA) patients might develop liver fibrosis or cirrhosis, requiring effective screening algorithms. AIMS: To assess the utility of non-invasive liver fibrosis assessment in RA patients on MTX. METHODS: Fifty-six patients were recruited from rheumatology outpatient clinics in a public tertiary centre from July 2017 to October 2018. Clinical data was collected. Screening for hepatic fibrosis was performed using transient elastography (TE), aminoaspartate transaminase to platelet ratio index (APRI), Hepascore and Fibrosis-4 index (FIB-4). Those with suspected significant liver fibrosis based on these screening tests were assessed by a hepatologist. RESULTS: Twenty-seven patients were suspected to have liver fibrosis on screening, including 10/56 (18%) by TE, 20/56 (36%) by Hepascore, 2/56 by APRI (4%) and 1/56 by FIB-4 (2%). Of these 27 patients, 11 were reviewed by a hepatologist and one diagnosed with significant liver fibrosis. TE, but not APRI, Hepascore or FIB-4, was found to have 100% sensitivity and 84% specificity (P = 0.029) for hepatologist-diagnosed liver fibrosis. CONCLUSION: Liver fibrosis develops in a minority of MTX-treated RA patients. The present study suggests that TE is a more sensitive screening test than APRI, FIB-4 or Hepascore in the identification of people with RA at risk of hepatic fibrosis.