Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Recommendations for enhanced primary series (third dose) COVID-19 vaccination for people with rheumatic diseases: Chapter of Rheumatologists, College of Physicians, Singapore.

Introduction: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. Methods: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. Results: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. Conclusion: These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.

Diffuse alveolar haemorrhage in systemic lupus erythematosus: A multicentre retrospective study in Singapore.

OBJECTIVE: Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival outcomes of SLE patients with DAH in Singapore. METHODS: We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups. RESULTS: A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25-54), with a median disease duration of 8.9 months (IQR: 0.13-102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6-46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026). CONCLUSIONS: The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

The Impact of the Off-site Monitoring Clinic (Virtual Monitoring Clinic) on the Practice of Outpatient Rheumatology in a Tertiary Centre during the COVID-19 Pandemic.

The ongoing pandemic in Singapore is part of a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To control the spread of COVID-19 and prevent the healthcare system from being overwhelmed, 'circuit breaker' measures were introduced between 7 April and 1 June 2020 in Singapore. There is thus a crucial need for innovative approaches to the provision and delivery of healthcare in the context of safe-distancing by harnessing telemedicine, especially for patients with chronic diseases who have traditionally been managed in tertiary institutions. We present a summary of how the Virtual Monitoring Clinic has benefited the practice of our outpatient rheumatology service during the COVID-19 pandemic. The virtual consultations address the need for safe-distancing by limiting face-to-face appointments and unnecessary exposure of patients to the hospital where feasible. This approach ensures that the patients are monitored appropriately for drug toxicities and side-effects, maintained on good disease control, and provided with patient education.

An evaluation of the effectiveness of teaching anatomy to rheumatologists through combined musculoskeletal sonoanatomy and human cadaveric dissection.

OBJECTIVE: Our aim was to evaluate the effectiveness of teaching anatomy through combined musculoskeletal sonoanatomy and human cadaveric dissection for rheumatologists practising musculoskeletal US. METHODS: The principal focus was on scanning and then dissecting relevant musculoskeletal structures. Outcomes measured included confidence levels and objective knowledge. A mixed-methods approach of evaluation and descriptive statistical data analysis was performed. RESULTS: The change in confidence ratings by delegates after the teaching event as represented by the mean difference (s.d.) (s.e.m.) for identification of surface anatomy was 1.846 (1.281) (0.355), with Student's paired t = 5.196 and P=0.000223. The mean difference (s.d.) (s.e.m) for performing IA injections was 1.538 (1.266) (0.351), with Student's paired t = 4.382, P=0.001, and for recognizing sonoanatomical structures it was 1.769 (1.235) (0.343), with Student's paired t = 5.165 and P= 0.000235. There was a significant increase in correct identification of anatomical and sonoanatomical knowledge in the pre- and post-course assessments. Rotator cuff interval region improved from 13 to 73%, P = 0.004; knee tendons insertion sites from 47 to 93%, P = 0.016; and muscles not adjacent to joints from 27 to 93%, P = 0.002. CONCLUSION: Dissection of joints enabled a three-dimensional relational mind map of the relevant regions of the human body, producing clarity in understanding regional relational topographic anatomy and sonoanatomy. The combination of US and cadaveric dissection improved learners' satisfaction, confidence and knowledge in areas where soft tissue complaints are common, which is likely to lead to accurate early diagnosis and cost-conscious, better overall care.

Back to the basics: Understanding joint swelling and tenderness at the wrist in rheumatoid arthritis through the use of ultrasonography.

AIM: To compare ultrasound-detected inflammation with clinical manifestations at the wrist in rheumatoid arthritis (RA). METHOD: Wrists assessed serially by assessors blinded to ultrasound findings were categorized into 4 groups: 1 = S0T0 (not swollen; not tender); 2 = S0T1 (not swollen; tender); 3 = S1T0 (swollen; not tender); 4 = S1T1 (swollen; tender). Ultrasound synovitis and tenosynovitis were graded semi-quantitatively (0-3) and dichotomously (0 or 1), respectively. The (a) power Doppler (PD), gray-scale (GS) and combined (PD + GS) ultrasound (CUS) scores and (b) their positivity (score > 0) were analyzed using a general linear repeated measures mixed model (a) assuming Gaussian errors and (b) with binary distribution and logit link, respectively. Pairwise comparisons among wrist groups were performed within context of the models. RESULTS: In 122 wrist assessments (baseline = 64; 3 months = 58) from 32 treated RA patients (87.5% female; mean disease duration 42.8 months), significant differences among groups for (a) scores were: 4 vs 1 (PD, P = 0.0031; GS, P = 0.0159; CUS, P = 0.0045), 4 vs 2 (PD, P = 0.0176; GS, P = 0.0160; CUS, P = 0.0074), and 4 vs 3 (CUS, P = 0.0374); and (b) positivity were: 4 vs 1 (PD, P = 0.0007), 4 vs 2 (PD, P = 0.0234), and 3 vs 1 (PD, P = 0.0202). No significant differences in results were found for groups 2 vs 1. No significant effects were attributable to differences in wrist side or follow-up visit. CONCLUSION: Ultrasound detected substantial inflammation when wrist joint swelling and tenderness are both present. Joint swelling without tenderness is associated with significantly more frequent PD detection. Without swelling, joint tenderness is not associated with a significantly greater degree of ultrasound-detected inflammation.

An evaluation of the Virtual Monitoring Clinic, a novel nurse-led service for monitoring patients with stable rheumatoid arthritis.

OBJECTIVES: To study clinical and patient reported outcomes for the Virtual Monitoring Clinic (VMC), a remote nurse-led telemonitoring service for monitoring Rheumatoid Arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients with stable RA enrolled in the VMC were followed up prospectively. The primary outcomes evaluated at 1-year follow-up were: Disease Activity Score-28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), and patient satisfaction assessed using an 11-point Likert scale. RESULTS: Of the 251 patients enrolled, 186 completed 1-year of follow-up. There was a 2.3% (n = 450) reduction in the annual workload from the rheumatology specialist outpatient clinic as a result of the VMC. Statistically significant improvement was seen in the mean patient satisfaction score (7.70-8.16, P ≤ 0.001), with 61.5% of patients opting for the VMC alternating with rheumatology outpatient clinic visits as their preferred mode of follow-up vis-à-vis standard care. There was a marginal increase in mean DAS28 and RAPID3 scores from 2.56 to 2.78 (P < 0.05) and 5.28 to 6.03 (P < 0.05), respectively. However, given that at 1-year follow-up more than half (72.0% and 63.4% based on DAS28 and RAPID3) of the patients' disease activity had improved or remained stable, and was in remission or low activity (73.1% and 53.2% based on DAS28 and RAPID3), the VMC seemed to maintain a stable RA disease activity for the majority of patients. CONCLUSIONS: The VMC is an effective and well-accepted novel approach for the management of patients with stable RA.

Greater rheumatoid arthritis joint improvement with more subjects achieving response across improvement categories using novel versus existing ultrasound methods.

We compared the change in joint inflammation and the proportion of subjects achieving threshold levels of improvement using the existing methods employing ultrasonography on pre-determined joint sites versus novel methods. These novel methods select the most affected joints based on (i) ultrasonography-the Individualized-Ultrasound (IUS) method, or (ii) ultrasonography and clinical joint assessment-the individualized-Composite-Ultrasound (ICUS) method. Mean 3-month change in total inflammation score (ΔTIS) and 95% CI was computed for each method on 24 RA subjects initiated or escalated on treatment. Individual improvement in TIS per subject, calculated as the 3-month ΔTIS divided by the maximum possible TIS score expressed as a percentage, was used to obtain the proportion of subjects achieving response across improvement categories. Mean 3-month ΔTIS was significantly greater (p values ranging from 0.0003 to 0.0026) for novel versus existing methods using 12- and 7-joint approaches. Using 12-joint approach, percentages of subjects in improvement categories ≥5%, ≥10%, ≥15% and ≥20% were, respectively, 50, 37.5, 12.5 and 8.3% for IUS; 58.3, 37.5, 12.5 and 8.3% for ICUS; and 16.7, 0, 0 and 0% for the existing method. Using 7-joint approach, the respective category percentages were 62.5, 37.5, 25 and 12.5% for IUS; 62.5, 41.7, 16.7 and 8.3% for ICUS; and 12.5, 4.2, 4.2 and 0% for the existing method. Novel ultrasound methods are more likely to detect improvement in joint inflammation, with more subjects achieving response across improvement categories, thereby representing a substantial advantage over the existing methods. However, this requires confirmation in larger RA cohorts.

Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical trials with ultrasound endpoints.

OBJECTIVES: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. METHODS: Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H0 : ES = 0 versus alternative hypotheses H1 : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. RESULTS: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. CONCLUSIONS: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.

Utility of ultrasonography in guiding modification of disease modifying anti-rheumatic drugs and steroid therapy for inflammatory arthritis in routine clinical practice.

OBJECTIVE: To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA) in routine clinical practice. METHODS: In this retrospective study, we analyzed DMARD and steroid use in IA patients referred to a rheumatologist-led ultrasound clinic. Power Doppler (PD) vascularity and greyscale (GS) synovial hypertrophy joint findings were categorized as positive/negative for each patient. The erythrocyte sedimentation rate (ESR) was used as a measure of disease activity. RESULTS: We assessed single visit data for 46 adult IA patients: 67.4% (n = 31) rheumatoid arthritis (RA), 15.2% (n = 7) psoriatic arthritis, 10.9% (n = 5) spondyloarthritis, and 6.5% (n = 3) undifferentiated IA. The mean ESR was 28.8 mm/h. Thirty-seven patients with both GS and PD ultrasound results were subsequently analyzed. All patients (n = 10) escalated and/or initiated on DMARD and 9/10 patients escalated or initiated on steroids were PD and GS positive. Six of seven patients with dose reduction and/or cessation of DMARDs and five of seven patients with dose reduction or cessation of steroids were PD negative. Of six patients who were GS positive and PD negative, three had dose reduction and/or cessation of DMARDs, while four had dose reduction of steroids; none of the six patients had DMARD/steroid escalation. CONCLUSION: By clarifying joint inflammation in an IA cohort with overall low ESR, ultrasonography of physician-selected joints can improve clinical assessment, resulting in treatment modification. Positive PD findings were particularly influential, while the clinical significance of GS positivity alone requires further investigation.

Dichotomous versus semi-quantitative scoring of ultrasound joint inflammation in rheumatoid arthritis using novel individualized joint selection methods.

The aim of the study is to compare the responsiveness of two joint inflammation scoring systems (dichotomous scoring (DS) versus semi-quantitative scoring (SQS)) using novel individualized ultrasound joint selection methods and existing ultrasound joint selection methods. Responsiveness measured by the standardized response means (SRMs) using the DS and the SQS system (for both the novel and existing ultrasound joint selection methods) was derived using the baseline and the 3-month total inflammatory scores from 20 rheumatoid arthritis patients. The relative SRM gain ratios (SRM-Gains) for both scoring system (DS and SQS) comparing the novel to the existing methods were computed. Both scoring systems (DS and SQS) demonstrated substantial SRM-Gains (ranged from 3.31 to 5.67 for the DS system and ranged from 1.82 to 3.26 for the SQS system). The SRMs using the novel methods ranged from 0.94 to 1.36 for the DS system and ranged from 0.89 to 1.11 for the SQS system. The SRMs using the existing methods ranged from 0.24 to 0.32 for the DS system and ranged from 0.34 to 0.49 for the SQS system. The DS system appears to achieve high responsiveness comparable to SQS for the novel individualized ultrasound joint selection methods.

Novel Ultrasound Joint Selection Methods Using a Reduced Joint Number Demonstrate Inflammatory Improvement when Compared to Existing Methods and Disease Activity Score at 28 Joints.

OBJECTIVE: A pilot study testing novel ultrasound (US) joint-selection methods in rheumatoid arthritis. METHODS: Responsiveness of novel [individualized US (IUS) and individualized composite US (ICUS)] methods were compared with existing US methods and the Disease Activity Score at 28 joints (DAS28) for 12 patients followed for 3 months. IUS selected up to 7 and 12 most ultrasonographically inflamed joints, while ICUS additionally incorporated clinically symptomatic joints. RESULTS: The existing, IUS, and ICUS methods' standardized response means were -0.39, -1.08, and -1.11, respectively, for 7 joints; -0.49, -1.00, and -1.16, respectively, for 12 joints; and -0.94 for DAS28. CONCLUSION: Novel methods effectively demonstrate inflammatory improvement when compared with existing methods and DAS28.

Use of magnetic resonance imaging in detecting subclinical synovitis in rheumatoid arthritis and correlation of imaging findings with interleukin-18 levels.

AIM: We studied the usefulness of magnetic resonance imaging (MRI) in detecting subclinical inflammation in patients with asymptomatic RA and tested the hypothesis of interleukin (IL)-18 as a marker of disease activity. METHODS: Thirteen RA patients with Disease Activity Score of 28 joints (DAS28) < 2.6 were evaluated. The patients underwent clinical evaluation, laboratory tests and MRI assessment. Imaging of bilateral hands and wrists was performed using validated acquisition and scoring techniques. Serum IL-18 levels were concurrently measured. RESULTS: MRI assessments showed that 92.3% and 76.9% of patients had synovitis and bone marrow edema, respectively, despite being in clinical remission. Eight out of 12 patients (66.7%) had erosions on MRI which were not visualised on plain radiographs. Of all the 182 joints studied for synovitis on MRI, only one had clinical evidence of joint swelling. Comparison of the total sum scores of synovitis between the right and left hand and wrist joints of individual patients showed a significant difference between the two sides. Measurements of IL-18 indicated that a large proportion (54%) of the patients had undetectable or very low levels of the cytokine. CONCLUSION: MRI is more sensitive in detecting erosions compared with X-rays, and is superior in its ability to detect subclinical inflammation in RA patients. Despite being in clinical remission, a large majority of patients had imaging-detected synovitis and bone marrow edema. Our study highlights the usefulness of MRI for the accurate evaluation of disease activity. In the utility of MRI, it may be important to assess bilateral hands and wrists, instead of limiting to the dominant side.

Pneumocystis jirovecii pneumonia in patients with autoimmune disease on high-dose glucocorticoid.

OBJECTIVE: Indications for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with autoimmune disease remain unclear. We aimed to determine (1) the incidence of PCP in patients with autoimmune disease in general, in a clinical setting where prophylaxis is not routine, and (2) whether high-dose glucocorticoid (≥30 mg oral prednisolone or equivalent per day) is a risk factor for PCP infection. METHODS: A retrospective review of the medical records of patients with autoimmune diseases hospitalized to a tertiary center over a 5-year study period was carried out. Patient demographics, mean glucocorticoid dose (in the last 1 month), and the outcomes of patients who developed PCP were analyzed. RESULTS: The incidence rate of PCP infection was 75 per 100,000 patients per year. The in-hospital mortality was 50%, and all those who died were on high-dose glucocorticoid at the time of PCP diagnosis. There was a significant difference between the occurrence of PCP in patients who were on high-dose vs non-high-dose glucocorticoid (df = 1, P = 0.009), with a relative risk of 19 (P = 0.010; 95% confidence interval, 2.0-182.8). The mean oral prednisolone dose of patients who developed PCP and those who did not were 55.5 versus 10.7 mg, respectively, P = 0.002. CONCLUSION: High-dose glucocorticoid may be associated with an increased risk of PCP infection in patients with autoimmune diseases.

Singapore Chapter of Rheumatologists Consensus Statement on the Eligibility for Government Subsidy of Biologic Disease Modifying Antirheumatic Agents for Treatment of Rheumatoid Arthritis (RA).

INTRODUCTION: Up to 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional non-biologic disease modifying antirheumatic drugs (nbDMARDs), and may benefit from therapy with biologic DMARDs (bDMARDs). However, the high cost of bDMARDs limits their widespread use. The Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore aims to define clinical eligibility for government-assisted funding of bDMARDs for local RA patients. MATERIALS AND METHODS: Evidence synthesis was performed by reviewing 7 published guidelines on use of biologics for RA. Using the modified RAND/UCLA Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations. RESULTS: Ten recommendations including diagnosis of RA, choice of disease activity measure, initiation and continuation of bDMARD and option of first and second-line therapies were formulated. The panellists agreed that a bDMARD is indicated if a patient has (1) active RA with a Disease Activity Score in 28 joints (DAS28) score of ≥3.2, (2) a minimum of 6 swollen and tender joints, and (3) has failed a minimum of 2 nbDMARD combinations of adequate dose regimen for at least 3 months each. To qualify for continued biologic therapy, a patient must have (1) documentation of DAS28 every 3 months and (2) at least a European League Against Rheumatism (EULAR) moderate response by 6 months after commencement of therapy. CONCLUSION: The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARDs usage accessible and equitable to eligible patients in Singapore.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.

OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter-observer reliability in scoring of synovitis. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at 0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. During image acquisition and interpretation, B-mode scoring showed ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.