Comparison of pregnancy outcomes between indigenous and non-indigenous lupus patients.

AIM: To compare pregnancy outcomes between IA and non IA lupus patients. BACKGROUND: Pregnancy in lupus patients confers an increased risk of maternal and fetal morbidity. There are no data on pregnancy outcomes for indigenous Australian (IA) patients with lupus. METHODS: Using state-wide longitudinal hospital morbidity data, we studied 702 pregnancies in IA (n = 31) and non-indigenous (NI) patients with lupus (n = 357) in Western Australia and compared rates for live birth (LB), preterm birth (PB) and gestational complications in the period 1985-2015. Results are presented as medians or frequency. RESULTS: IA patients had proportionally more pre-existing renal disease (35 vs 13%, P < 0.01) and lower socio-economic status (P = 0.02). Age at first pregnancy was lower in IA patients (27 vs 30 years, P < 0.001), recorded gravidity was similar (2 vs 2, P > 0.6) and elective termination (n = 138) was more frequent in NI than IA pregnancies (21.1 vs 4.8%, P < 0.01). For continued pregnancies (59 in IA and 505 in NI), respective outcomes were as follows: LB 84.7% versus 91.5% (P = 0.15), spontaneous abortion 13.5% versus 6.9% (P = 0.13), (pre-)eclampsia 8% versus 9.9% (P = 0.89), PB 12% versus 13.4% (P = 0.98) and caesarean delivery 30% versus 47.2% (P = 0.02). Gestational diabetes (26% vs 6.1%), renal flares (20% vs 5.6%) and infections (22% vs 6.3%) were all more frequent in IA lupus pregnancies (all P < 0.001). CONCLUSIONS: The burden of comorbidities was higher in IA patients with lupus due to renal flares, gestational DM and infections. Although PB rates were overall high, they were, however, similar for IA and NI lupus pregnancies, as were LB rates.

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.

Long-term incidence, risk factors and complications for venous thromboembolism in patients with systemic lupus erythematosus.

AIM: To compare frequency, incidence rates (IR), risk factors and outcomes of a first venous thromboembolic event (VTE) between patients with systemic lupus erythematosus (SLE) and controls. METHODS: Using state-wide longitudinal hospital data from Western Australia (WA), we recorded venous thrombosis (VT) and pulmonary embolism (PE) in patients with SLE (n = 1854, median age 40, 86% female) and matched hospitalised controls (n = 12,107, median age 40 years, females 88.6%) in the period 1985-2015. Results presented are medians, frequency, IR per 1000 person years (PY) and odds, rate, or adjusted hazard ratios (OR/RR/a-HR) with 95% confidence intervals (CI). RESULTS: Patients with SLE had significantly higher odds (12.8 vs 3.3%; OR 4.26, CI 3.60-5.05) and IR for a first VTE (10.09 vs 1.52; RR 6.64; CI 5.56-7.79). Over the three study decades, the IR for PE declined in patients with SLE from 7.74 to 3.75/1000 PY (p < .01) with no changes observed for VT or in controls. VTE recurred more frequently in patients with SLE (24.1% vs 10.2 %) (p < .01). Antiphospholipid antibodies (aPL) (a-HR 4.24, CI 2.50-7.19), serositis (a-HR 2.70, CI 1.86-3.91), lupus nephritis (a-HR 1.75 CI 1.25-2.33) and thrombocytopenia (a-HR 1.65 (1.10-2.49) were the strongest disease risk factors for VTE only in patients with SLE, while arterial hypertension, smoking and obesity were independent VTE risk factors for both groups. VTE was not associated with an increased risk for arterial events, but PE increased the risk for pulmonary hypertension (PH) in both patients with SLE (a-HR 6.47, CI 3.73-11.23) and controls (a-HR 9.09, CI 3.50-23.63). VTE increased the risk of death in both patients with SLE (a-HR 2.02, CI 1.50-2.70) and controls (a-HR 6.63, CI 5.21-8.42) after 10 years of follow-up. CONCLUSIONS: VTE affected 12.8% of patients with SLE at six times the VTE rate in controls with aPL as the strongest, but not the only risk factor in SLE. The risk of PH was increased in both groups following PE, but VTE did not associate with an increased risk of arterial events.

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.

Cancer Risk and Mortality in Hospitalized Patients With Idiopathic Inflammatory Myopathies in Western Australia.

OBJECTIVE: To compare cancer incidence, type, and survival between patients with idiopathic inflammatory myopathies (IIMs) in Western Australia (WA) and the general population. METHODS: Administrative health data for hospitalized patients with incident IIM (n = 803, 56.5% female, median age 62.0 yrs), classified by a validated algorithm as polymyositis (PM; 36.2%), dermatomyositis (DM; 27.4%), inclusion body myositis (IBM; 17.1%), overlap myositis (OM; 10.7%), and other IIM (8.6%), were linked to WA cancer and death registries for the period of 1980 to 2014. Cancer incidence rates (CIRs) before and after IIM diagnosis as well as cancer mortality were compared with age-, sex-, and calendar year-matched controls (n = 3225, 54.9% female, median age 64 yrs) by rate ratios (RRs) and Kaplan-Meier survival estimates. RESULTS: The prediagnosis CIR was similar for patients with IIM and controls (6.57 vs 5.95; RR 1.11, 95% CI 0.88-1.39) and for patients evolving to DM (n = 220) or other IIM subtypes (6.59 vs 6.56; RR 1.01, 95% CI 0.38-3.69). During follow-up, CIR was higher for all DM (4.05, 95% CI 3.04-5.29), with increased CIR for lung cancer vs controls (1.05 vs 0.33; RR 3.18, 95% CI 1.71-5.47). Cancer post diagnosis shortened life span by 59 months for patients with IIM (103 vs 162 months, P < 0.01), but reduced survival rates were observed only in patients with DM and IBM. CONCLUSION: Cancer risk was not increased prior to IIM, but CIR for lung cancer was increased following DM diagnosis. As cancer reduced survival only in patients with DM and IBM, these data support a strategy of limited cancer screening in IIM.

Joint surgery rates in lupus: a long-term cohort study.

AIM: With scarce data on the need and type of joint surgery in SLE, we investigated the long-term rates and underlying causes for arthroplasty, arthrodesis and synovectomy in patients with SLE. METHODS: Procedure dates for arthroplasty, arthrodesis or synovectomy were retrieved from the state-wide Hospital Morbidity Data Collection between 1985 and 2015 for patients with SLE (n=1855) and propensity-matched controls (n=12 840). Patients with SLE with ≥two additional diagnostic codes for rheumatoid arthritis were classified as rhupus. ORs and incidence rates (IRs) per 100 person-years for joint procedures (JPs) were compared among patients with rhupus, patients with other SLE and controls across three study decades by regression analysis. RESULTS: More patients with SLE than controls underwent a JP (11.6% vs 1.3%; OR 10.8, CI 8.86 to 13.24) with a higher IR for JP in patients with SLE (1.9 vs 0.1, rate ratio 19.9, CI 16.83 to 23.55). Among patients with SLE, patients with rhupus (n=120, 60.5%) had the highest odds of arthroplasty (OR 4.49, CI 2.87 to 6.92), arthrodesis (OR 6.64, CI 3.28 to 12.97) and synovectomy (OR 9.02,CI 4.32 to 18.23). Over time, the IR for overall JP in patients with rhupus was unchanged (8.7 to 8.6, R2=0.004, p=0.98), although the IR for avascular necrosis underlying arthroplasty decreased for all patients with SLE (0.52 to 0.10, p=0.02). Patients with other SLE also had significantly higher OR and IR for all three JPs than controls with insignificant decreases in synovectomy and increases in arthroplasty over time in this group. CONCLUSIONS: The overall burden of joint surgery in SLE is high and despite a reduction in avascular necrosis, arthroplasty and arthrodesis rates have not decreased over time. These data indicate a need for increased efforts to prevent joint damage in patients with lupus.

The spectrum of idiopathic inflammatory myopathies in Western Australia: epidemiological characteristics and mortality over time.

To determine long term overall and subgroup specific incidence rates and associated mortality for idiopathic inflammatory myopathies (IIM) in a population wide study. We included patients hospitalised between 1980 and 2015 with incident IIM as defined by relevant diagnostic codes for dermatomyositis (DM) polymyositis (PM), inclusion body myositis (IBM), other IIM and overlap myositis (OM) in the Western Australia Health Hospital Morbidity Data Collection (n = 846). Trends over time for annual incidence rate per million population (AIR) were analysed by least square regression and Kaplan-Meier survival and mortality rates (MR)/100 person years compared with a matched control group (n = 3681). The averaged AIR for all IIM was 19 (CI 10.4-27.5) and stable over time with point prevalence reaching 205.3 (CI 185.6-226.6) per million in 2015. Over time, the AIR for DM 5.0 (CI 0.6-9.4) and IBM 3.3 (CI 0.7-9.6) was stable, while AIR decreased for PM (p < 0.01) and increased for other IIM (p < 0.01) and OM (p < 0.01). IBM patients were eldest at diagnosis (68 years, CI 59-77) with male preponderance in IBM (53.4%) and other IIM (55.8%) groups. Crude mortality (54.5 vs 41.3%), MR ratio (6.65 vs 5.91) and 5 (65.8% vs 71.6%) and 10-year (52.5% vs 58.7%) survival were all worse for IIM patients (all p < 0.05). IBM patients had highest MR (10.1; CI 8.38-12.14) and lowest 10-year survival (39.2%). While cardiovascular disease and cancer were predominant causes of death, they were proportionally lower in IIM patients, where respiratory and rheumatic disease were more frequent causes of death. While the overall incidence of IIM in WA was stable over 35 years, the spectrum of IIM has changed significantly with increases especially in other IIM and OM. The overall prognosis with IIM remains guarded with 10-year survival just over 50%.

Cancer development in patients hospitalized with systemic lupus erythematosus: A population-level data linkage study.

AIM: To explore the association between systemic lupus erythematosus (SLE) with the risk of cancer development and subsequent 5-year mortality in Western Australia (WA). METHODS: Population-level, data linkage study of SLE patients (n = 2111) and general population comparators (n = 21 110) hospitalized between 1980 and 2014. SLE patients (identified by ICD-9-CM: 695.4, 710.0, and ICD-10-AM: L93.0, M32.0) were nearest matched (10:1) for age, sex, Aboriginality, and temporality. Follow up was from time zero (index SLE hospitalization) to cancer development, death or 31 December 2014. We assessed the risk of cancer development and subsequent 5-year mortality between SLE patients and comparators with univariate and multivariate-adjusted Cox proportional hazards regression models. RESULTS: SLE patients had similar multivariate-adjusted risk (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.93-1.15; p = .583) of cancer development. Cancer development risk was higher in SLE patients <40 years old (aHR 1.58, 95% CI 1.29-1.94; p < .001), and from 1980 to 1999 (aHR 1.16, 95% CI 1.02-1.31; p < .001). SLE patients had higher risk of developing cancer of the oropharynx (aHR 2.13, 95% CI 1.30-3.50), vulvo-vagina (aHR 3.22, 95% CI 1.34-7.75), skin (aHR 1.20, 95% CI 1.01-1.43), musculoskeletal tissues (aHR 2.26, 95% CI 1.16-4.40), and hematological tissues (aHR 1.78 95% CI 1.25-2.53), all p < .05. After cancer development, SLE patients had increased risk of 5-year mortality (aHR 1.31, 95% CI 1.06-1.61); highest in patients <50 years old (aHR 2.03, 95% CI 1.03-4.00), and in those with reproductive system and skin cancers. CONCLUSIONS: Hospitalized SLE patients had increased risk of multiple cancer sub-types. Following cancer development, SLE patients had increased risk of 5-year mortality. There is scope to improve cancer prevention and surveillance in SLE patients. TRIAL REGISTRATION: Not applicable. This low-risk risk study used de-identified administrative linked health data.

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.

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.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2).

The persistence of immunogenicity in patients with immune-mediated inflammatory diseases (IMID) on disease-modifying antirheumatic therapy (DMARD) has been less well studied. This extension study evaluates the SARS-CoV2 antibody decay kinetics 6 months following two doses of ChAdO1nCov-19 (AZ) and BNT162b (Pfizer) and subsequent response following an mRNA booster. RESULTS: 175 participants were included. Six months after initial AZ vaccination, 87.5%, 85.4% and 79.2% (p=0.756) in the withhold, continue and control groups remained seropositive compared with 91.4%, 100% and 100% (p=0.226), respectively, in the Pfizer group. Both vaccine groups developed robust humoral immune responses following a booster with seroconversion rates being 100% for all three intervention categories. The mean SARS-CoV-2 antibody levels were significantly lower in the targeted synthetic DMARD (tsDMARD) group that continued therapy compared with the control (2.2 vs 4.8 U/mL, p=0.010). The mean time interval until loss of protective antibodies in the IMID group was 61 days for the AZ and 137.5 days for the Pfizer vaccine. Within each DMARD class the interval until loss of protective antibody titres in the csDMARD, bDMARD and tsDMARD groups were 68.3, 71.8 and 64.0 days in the AZ group and 185.5, 137.5 and 116.0 days in the Pfizer group, respectively. CONCLUSION: Antibody persistence was longer in the Pfizer group due to a higher peak antibody level following second vaccination with levels of protection in IMID on DMARD therapy similar to controls except in those on tsDMARDs where it was lower. A third mRNA vaccine booster can restore immunity in all groups.

Systemic juvenile idiopathic arthritis: frequency and long-term outcome in Western Australia.

Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.

The effect of TNF treatment uptake on incident hospital admission in Western Australia.

OBJECTIVE: Treatment strategies for juvenile idiopathic arthritis (JIA) have shifted significantly over the last 20 years. We examined the effect of the introduction of government-subsidised TNF inhibitor (TNFi) treatment on incident hospitalisation for JIA. METHODS: Western Australian (WA) hospital data were used to identify patients < 16 years hospitalised with JIA between 1990 and 2012. Changes in the number of patients with an incident hospitalisation, overall admissions and admissions for joint aspiration were examined using join-point regression TNFi dispensing data from 2002-2012 was used to describe defined daily doses (DDD)/1000 population/day. RESULTS: We included 786 patients (59.2% girls, median age 8 years) with a first-time admission with JIA. The annual incident admission rate was 7.9 per 100,000 person-years (95%CI: 7.3, 8.4) which did not change significantly between 1990 and 2012 (annual percentage change (APC): 1.3, 95%CI: -0.3, 2.8). Annual hospital-based prevalence of JIA reached 0.72/1000 in 2012. DDD for TNFi usage rose steadily from 2003 indicating TNFi usage by 1/2700 children in 2012, while overall admission rates (APC 3.7; 95%CI: 2.3, 5.1) and admission rates for joint injections (APC 4.9%; 95%CI: 3.8, 6.0) also increased significantly in that period. CONCLUSION: Incident inpatient admission rates for JIA were stable over a 22-year period. The uptake of TNFi was not associated with lower admission rates for JIA, due mainly to an increase in admissions for joint injection. These results indicate a notable but unexpected change in hospital-based management of JIA since the introduction of TNFi therapy in WA, where hospital-based prevalence of JIA is slightly higher than in North America.

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.

The prevalence of rheumatoid arthritis in Western Australia.

BACKGROUND: Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis, but the prevalence in Australia is unknown. We estimated RA period prevalence and identified factors associated with frequent RA hospitalisations, using linked administrative health and state-specific Australian Pharmaceutical Benefits Scheme (PBS) datasets in Western Australia (WA) from 1995 to 2014. METHODS: This was a longitudinal population-based cohort study using two independent datasets to identify prevalent RA patients. RA prevalence was calculated per 1000 hospital separations and biological therapy users. RA patients were identified in the WA linked health dataset using ICD codes 714.0-714.9 and M05.00-M06.99. Dispensing data on biological therapy for RA were obtained from PBS records and converted to defined daily doses /1000 population/day. Multivariable logistic regression was used to analyse factors associated with frequent RA hospitalisations (> 2/year), controlling for sex, age, and geographic locations. Potential interactions were assessed using logistic regression in a stepwise approach. RESULTS: A total of 17,125 RA patients had 50,353 hospital separations between 1995 and 2014, averaging three hospitalisations per patient over 20 years. The RA period prevalence was 3.4 per 1000 separations (0.34%; 95% CI 0.33-0.34), while the RA period prevalence based on biological therapy use was 0.36% (95% CI 0.35-0.37). The corrected RA prevalence based on biological therapy usage was 0.36% (95% CI 0.35-0.37) for the 2005-2009 and increased to 0.72% (95% CI 0.70-0.74) in 2010-2014 period. Associated factors for frequent RA hospitalisations were being female [1.21 (95% CI 1.15-1.26)], aged 60-69 years [4.45 (95% CI 3.74-5.30)], living in rural areas [1.12 (95% CI 1.02-1.24)]. The odd ratio of interaction between these associated factors was 1.34 (95% CI 1.16-1.55). CONCLUSION: The minimal prevalence of RA in Western Australia is 0.34-0.36%, which falls within the literature range. Older female RA patients in rural were more likely to be hospitalised, suggesting unmet primary care for needs.

Adult-onset Still's disease in Western Australia: Epidemiology, comorbidity and long-term outcome.

AIM: Adult-onset Still's disease (ASD) is a rare, potentially life-threatening autoinflammatory condition. As reported prevalence shows regional variation and long-term outcome data are scarce, we investigated epidemiology and long-term health outcomes of ASD in Western Australia (WA). METHODS: Population-based cohort study using longitudinally linked administrative health data from all WA hospitals between 1999 and 2013 for ASD patients (ICD-10-AM M06.1) and controls matched for age, gender, and index year. Rate ratios and odds ratios (RR/OR) with 95% confidence intervals (CI) compared ASD patients with controls. RESULTS: The average ASD incidence (n = 52) was 0.22/100 000 with 2.4/100 000 point-prevalence as of December 31, 2013. ASD patients (median age 41.5 years, 59.6% female) had higher odds of previous liver disease (OR 2.67, 95% CI 1.31-5.45), fever (OR 54.10, 95% CI 6.60-433.0), rash (OR 15.70, 95% CI 4.08-60.80), and serious infections (OR 4.36, 95% CI 2.11-22.80) than controls. Despite biological disease-modifying antirheumatic drugs in 27% of patients, ASD patients had higher odds for joint replacement (n = 7, 13.5%) (OR 45.5, 95% CI 4.57-93.70), osteoporosis (OR 31.3, 95% CI 3.43-97), and serious infections (RR 5.68; 95% CI 6.61-8.74) during follow up. However, crude mortality (11.5% vs 7.5%; P = 0.34), survival at 1 and 5 years (P= 0.78), and last modified Charlson Comorbidity score (median 2 vs 2) were similar between groups. CONCLUSION: The epidemiology and demographics of ASD in Western Australia fall within the internationally reported range. ASD patients present increased rates of liver disease, rash, and serious infections before disease onset. Mortality following ASD was not increased for 5 years despite high rates of chronic arthritis requiring joint replacement, serious infections, and osteoporosis.

Temporal trends in hospitalisation for opportunistic infections in lupus patients in Western Australia.

BACKGROUND: Lupus patients often require aggressive immunosuppressive therapy, which increases the risk for infections. We studied the temporal rates for opportunistic infections (OI) and associated mortality in lupus patients hospitalised in Western Australia. METHODS: All patients hospitalized in the period 1985-2015 with ≥2 ICD based diagnostic codes for SLE were included. OI was defined as a microbiologically confirmed mycobacterial, fungal, or viral infection. Descriptive data are given as median (IQR) and frequency (%) with incidence rates (IR) calculated per 1000 person years and IR trend rates analysed across 10-year periods by least square regression (R2). RESULTS: The study cohort (n = 1408) contained 85.3% females with age at entry 35 years (IQR 22-51). During median follow-up of 21.1 years (IQR 17.5-29.6) hospitalisation for OI occurred in 121 (8.6%) patients with recurrent or multiple OI observed in 42 (34.7%) patients. During 29.771 thousand person years, a total of 295 OI were diagnosed for an overall IR rate of 9.91 (CI 8.82-11.09)/1000 person years which did not decrease significantly over time (R2 0.14). Significant decreases were however seen in the IR for tuberculosis (R2 0.88), cryptococcal (R2 0.98) and pneumocystis (R2 0.98) infections, with increasing IR observed for other mycobacteria (R2 0.99) and aspergillosis (R2 0.55) and little change seen for H Zoster (R2 0.18) and Varicella (R2 0.10) infections. In-hospital death during OI admission occurred in 9/121 patients (7.4%). There was no significant gender difference in IR or outcome of OI. CONCLUSIONS: Hospitalization rates for OI in lupus patients have not changed significantly over time, but there has been a clear shift in the underlying OI. The decrease in mycobacterial and pneumocystis infections suggest successful prophylaxis but the increase in viral and mycotic infections indicate a sustained need to improve prevention of these OI in lupus patients.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease (RESCUE).

OBJECTIVE: To assess the antibody response to disease-modifying antirheumatic drug (DMARD) therapy after the first and second dose of the ChAdOx1nCov-19 (AstraZeneca (AZ)) and BNT162b (Pfizer) vaccines in patients with immune-mediated inflammatory disease (IMID) compared with controls and if withholding therapy following the first vaccination dose has any effect on seroconversion and SARS-CoV-2 antibody (Ab) levels. METHODS: A multicentre three-arm randomised controlled trial compared the immunogenicity of the Pfizer and AZ vaccines in adult patients on conventional synthetic (csDMARD), biologic (bDMARD) or targeted synthetic (tsDMARD) therapy for IMID (n=181) with a control group (n=59). Patients were randomised to continue or withhold DMARD therapy for 1-2 weeks post first dose vaccination only. Serum SARS-CoV-2 IgG detection (IgG ≥1.0 U/mL) and titres against the S1/S2 proteins were measured at baseline, 3-4 weeks post first vaccination and 4 weeks post second vaccination. RESULTS: AZ vaccination was given to 47.5%, 41.5% and 52.5% in the continue, withhold and control groups, respectively while Pfizer vaccination was given to 52.5%, 58.5% and 47.5% among the continue, withhold and control groups, respectively. Seroconversion rates following the first dose in the AZ and Pfizer groups were only 27.3% vs 79.2% (p=0.000) and 64.58% vs 100% (p=0.000), respectively in the IMID groups who continued therapy compared with the AZ and Pfizer controls, respectively. Withholding DMARD therapy following the first vaccination dose resulted in higher seroconversion to 67.7% and 84.1% in the AZ and Pfizer groups, respectively. Following the second AZ and Pfizer vaccinations when all DMARDs were continued, despite a slightly lower seroconversion rate (83.7% vs 100%, p=0.000 and 95.9% vs 100%, p=0.413), respectively, the mean SARS-CoV2 IgG Ab titres were not significantly different in the csDMARD and bDMARD groups compared with the controls regardless of hold while it was significantly lower in patients taking tsDMARD (12.88 vs 79.49 U/mL, p=0.000). CONCLUSIONS: Following the first vaccination dose, antibody responses were lower in IMID on DMARD therapy, however the final responses were excellent regardless of hold with the exception of the tsDMARD group where withholding therapy is recommended. At least 2 vaccinations are therefore recommended preferably with an messenger RNA vaccine. TRIAL REGISTRATION NUMBER: ANZCTR: 12621000661875.

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.