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.

Recommendations for COVID-19 vaccination in people with rheumatic disease: Developed by the Singapore Chapter of Rheumatologists.

AIM: People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD. METHODS: Systematic literature reviews were performed to evaluate: (a) outcomes in PRD with COVID-19; (b) efficacy, immunogenicity and safety of COVID-19 vaccination; and (c) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: The consensus comprises 2 overarching principles and 7 recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommend that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommend that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titers against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference. CONCLUSION: These recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence.

Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis.

AIM: There have been major advances in biologic treatment options for psoriatic arthritis (PsA) since the publication of the 2015 consensus recommendations by the Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore, for government-assisted funding, thus warranting a revision of this guideline. METHODS: Recent trials and nine published guidelines on the use of biologic therapy for PsA were reviewed. Based on the synthesized evidence, a task force panel (TFP), consisting of 10 practicing rheumatologists in Singapore, rated the statements pertaining to the use of biologic therapy, using a modified Delphi approach. Consensus was obtained if >70% agreed on a statement. RESULTS: The TFP agreed on 10 recommendations pertaining to the initiation, choice and continuation of biologic therapy. A biologic is indicated in patients with PsA: (a) with at least three swollen and tender joints, digits or entheses; and (b) who have failed at least two conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) strategies for a minimum of 3 months each. Any approved drug class including tumor necrosis factor inhibitors, interleukin-17 inhibitors (IL-17i), IL-12/23i or targeted synthetic DMARDs may be considered as first-line treatment, and continued only if a response is achieved by 6 months. CONCLUSION: These recommendations developed through a formal consensus method may be useful to guide funding considerations for appropriate and equitable use of biologic therapy for eligible patients with PsA.

Update on recommendations for eligibility of government subsidization of biologic disease-modifying antirheumatic drugs for the treatment of axial spondyloarthritis in Singapore.

AIMS: The field of axial spondyloarthritis (axSpA) has undergone significant changes recently in particular with disease classification, assessment of disease activity and increased treatment options for biologics. In order to reflect these developments, we aimed to update the local consensus recommendations for subsidization of biologics. METHODS: A modified Delphi approach was used. Six published guidelines from major rheumatology societies and healthcare authorities on axSpA were reviewed. Findings were synthesized and used in formulating updated recommendation statements. Recommendations were rated by 10 practicing rheumatologists in Singapore. Consensus was reached if there was more than 70% agreement or disagreement. RESULTS: Ten statements achieved consensus. Patients may be considered for subsidization of biologic therapy if they fulfill the Assessment of Spondyloarthritis International Society or modified New York criteria, with persistently active disease (defined either by Ankylosing Spondylitis Disease Activity Score ≥ 2.1 or Bath Spondylitis Disease Activity Index ≥ 4), despite 4 weeks of full-dose non-steroidal anti-inflammatory drugs and regular exercise. Either tumor necrosis factor inhibitors or interleukin 17 inhibitors may be used as first-line therapy, and should be continued if adequate response is achieved at 6 months. CONCLUSION: Recommendation statements were formulated through a formal consensus process by local experts with a view to assist relevant authorities in funding considerations and for use in clinical practice.

Singapore Chapter of Rheumatologists updated consensus statement on the eligibility for government subsidization of biologic and targeted-synthetic therapy for the treatment of rheumatoid arthritis.

INTRODUCTION: Approximately 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARDs). However, widespread use of biologic DMARDs (bDMARDs) and targeted-synthetic (tsDMARDs) is limited by cost. We formulated updated recommendations for eligibility criteria for government-assisted funding of bDMARDs/tsDMARDs for RA patients in Singapore. MATERIALS AND METHODS: Published guidelines regarding use of bDMARD and tsDMARDs were reviewed. We excluded those without a systematic literature review, formal consensus process or evidence grading. Separately, unpublished national reimbursement guidelines were included. RESULTS: Eleven recommendations regarding choice of disease activity measure, initiation, order of selection and continuation of bDMARD/tsDMARDs were formulated. A bDMARD/tsDMARD is indicated if a patient has: (a) at least moderately active RA with a Disease Activity Score in 28 joints/erythrocyte sedimentation rate (DAS28-ESR) score of ≥3.2; (b) failed ≥2 csDMARD strategies, 1 of which must be a combination; (c) received an adequate dose regimen of ≥3 months for each strategy. For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered. If a first-line TNFi fails, options include another TNFi, non-TNFi biologic or tsDMARDs. If a first-line non-TNFi biologic or tsDMARD fails, options include TNFi or another non-TNF biologic or tsDMARD. For continued bDMARD/tsDMARD subsidization, a patient must have a documented DAS28-ESR every 3 months and at least a moderate European League Against Rheumatism response by 6 months. CONCLUSION: These recommendations are useful for guiding funding decisions, making bDMARD/tsDMARDs usage accessible and equitable in RA patients who fail csDMARDs.

Singapore Chapter of Rheumatologists consensus statement on the eligibility for government subsidy of biologic disease modifying anti-rheumatic agents for the treatment of psoriatic arthritis.

AIM: In Singapore, patients with psoriatic arthritis (PsA) constitute a significant disease burden. There is good evidence for the efficacy of anti-tumor necrosis factor (anti-TNF) in PsA; however cost remains a limiting factor. Non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) hence remain the first-line treatment option in PsA in spite of limited evidence. The Singapore Chapter of Rheumatologists aims to develop national guidelines for clinical eligibility for government-assisted funding of biologic disease modifying anti- rheumatic drugs (bDMARDs) for PsA patients in Singapore. METHODS: Evidence synthesis was performed by reviewing seven published guidelines on use of biologics for PsA. Using the modified Research and Development/University of California at Los Angeles 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 were formulated relating to initiation, continuation and options of bDMARD therapy. The panellists agreed that a bDMARD is indicated if a patient has active PsA with at least five swollen and tender joints, digits or entheses and has failed two nbDMARD strategies at optimal doses for at least 3 months each. Any anti-TNF may be used and therapy may be continued if an adequate PsARC response is achieved by 3 months after commencement. 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 bDMARD usage accessible and equitable to eligible patients in Singapore.

Consensus development on eligibility of government subsidisation of biologic disease modifying anti-rheumatic agents for treatment of ankylosing spondylitis: The Singapore experience.

INTRODUCTION: The beneficial effects of biologic disease-modifying anti-rheumatic drugs (bDMARDs), such as tumour necrosis factor inhibitors (anti-TNF) in active ankylosing spondylitis (AS) are well established. The significant costs on patients in the absence of financial subsidization can limit their use. The objective was to describe a consensus development process on recommendations for government-assisted funding of biologic therapy for AS patients in Singapore. METHODS: Evidence synthesis followed by a modified RAND/UCLA Appropriateness Method (RAM) was used. Eleven rheumatologists rated indications for therapies for different proposed clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate 10 practice recommendations. RESULTS: It was agreed that a bDMARD (anti-TNF) is indicated if a patient has active AS with a Bath Ankylosing Spondylitis Activity Index (BASDAI) ≥ 4 and spinal pain of ≥ 4 cm on visual analogue scale (VAS) on two occasions at least 12 weeks apart, despite being on a minimum of two sequential non-steroidal anti-inflammatory drugs at maximal tolerated dose for at least 4 weeks, in addition to adherence to an appropriate physiotherapy program for at least 3 months. To qualify for continued biologic therapy, a patient must have documentation of response every 3 months and at least 50% improvement in BASDAI and reduction of spinal pain VAS ≥ 2 cm. CONCLUSION: A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context.

COX2 Inhibitors as Anti-Inflammatory Agents

Pain and inflammation are common problems in clinical practice. Anti-inflammatory drugs are one of the most often prescribed groups of medications. The issue is that they carry gastrointestinal (GI) and cardiovascular (CV) risks. Therefore, anti-inflammatory drugs should be used mostly in the setting of inflammation. Non inflammatory pain can be managed with other groups of drugs and therapies. For patients who do need anti-inflammatory agents, the choice is dependent on the GI and CV risk profile of the patient. Where possible, efforts should be directed to the underlying cause of the pain and inflammation.

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.

The use of biological agents in the treatment of rheumatoid arthritis.

Rheumatoid arthritis is a common and potentially devastating condition which did not have good treatment options until recently. Pharmacological treatment should not just comprise antiinflammatory agents and corticosteroids. The current therapeutic approach is to start a disease modifying agent early in the illness to prevent eventual joint damage. Older disease modifying anti-rheumatic drugs (DMARDs) include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporine are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents which block certain key molecules involved in the pathogenesis of the illness. They include tumour necrosis factor (TNF)- blocking agents such as infliximab, etanercept and adalimumab, the anti-CD 20 agent rituximab and CTLA-4 Ig abatacept. Other agents which are in development include anti-IL6 tocilizumab, anti-CD22 and anti-lymphostat B. In this review, the efficacy and side effects of these agents, their impact on current clinical practice and future trends are discussed.

Awareness and health beliefs of women towards osteoporosis.

A population-based survey was conducted to determine the awareness, knowledge of risk factors, and attitudes toward osteoporosis in middle-aged and elderly women in Singapore. Chinese women aged 45 years and above ( n=1,376) living in Teban Gardens (community on the western side of Singapore) were randomly sampled. Household interviews were conducted and questions on socioeconomic status, knowledge of osteoporosis, identification of risk factors for osteoporosis, and health beliefs were assessed. There were 946 (68.8%) women who were postmenopausal and 430 (31.2%) who were not. Fifty-eight percent of the sample had heard of osteoporosis. Women who were younger, better educated, who exercised regularly, or who were single were more likely to have heard of osteoporosis. The main sources of information about osteoporosis were the mass media and friends. The identification of risk factors ranged from fair to good: 85.7% of women identified low calcium intake, 43.7% identified lack of exercise, and 30.5% identified family history of osteoporosis as risk factors for osteoporosis. Most women (79.1%) were concerned about developing osteoporosis but only 15.2% thought that osteoporosis was more serious than cancer. Community-based health education programs on osteoporosis that target a wide audience including the less well educated, could be implemented. Increasing the awareness of osteoporosis and its risk factors may be essential in efforts to decrease the incidence of this disease.

Quality of life in an urban Asian population: the impact of ethnicity and socio-economic status.

The relationships between ethnicity, socio-economic status (SES) and health-related quality of life (HRQoL) have not been well characterised in most Asian populations. We therefore studied the influence of ethnicity and SES on HRQoL in a multi-ethnic urban Asian population, adjusting for the influence of other known determinants of HRQoL. In a disproportionately stratified, cross-sectional, population-based survey, Chinese, Malay and Indian subjects in Singapore completed the Short Form 36 Health Survey (SF-36) HRQoL measure and were assessed to determine demographic, socio-economic, psychosocial and other characteristics. Multiple linear regression models were used to study the influence of ethnicity and SES on SF-36 scores while adjusting for the influence of other determinants of HRQoL. The survey participation rate was 92.8%. Ethnic differences in HRQoL were present for all 8 SF-36 scales (p<0.001 for all scales except General Health) among the 4122 Chinese, Malays and Indians surveyed. These ethnic groups also differed in several known determinants of HRQoL (e.g., Chinese had more years of education and Indians had more chronic medical conditions). After adjusting for the influence of these factors, ethnicity and SES independently influenced HRQoL, with mean differences in SF-36 scores due to ethnicity ranging from 1.4 to 13.1 points. Educational level and housing type (markers of SES) were also associated with SF-36 scores (0.5-0.6 point increase per year of education and 3.5-4.0 point increase with better housing type, respectively). Better HRQoL was also associated with better family support, and poorer HRQoL with acute and chronic medical conditions and sick days. The study concludes that ethnicity and SES are associated with clinically important differences in HRQoL in a multi-ethnic, urban Asian population.

Does being bilingual in English and Chinese influence responses to Quality-of-Life scales?

BACKGROUND: It is not known if the inclusion of bilinguals affects the results of research using Quality-of-Life (QoL) scales. OBJECTIVE: To determine the influence of bilingualism on responses to a QoL scale. RESEARCH DESIGN: In this cross sectional study, a population-based, disproportionately stratified random sample of monolingual and bilingual ethnic Chinese completed the Short-Form 36 Health Survey (SF-36) in English or Chinese (representing an alphabet and pictogram based language respectively). Cumulative logit regression models were used to assess the influence of bilingualism on SF-36 scores, while adjusting for the influence of questionnaire language and known determinants of QoL. RESULTS: English or Chinese SF-36 versions were completed by 1331 and 1380 subjects respectively (49% female, aged 21-65 years, 1366 bilingual, 501 English monolingual, 844 Chinese monolingual), with response rates exceeding 85%. Fifty percent of subjects were bilingual. Bilinguals differed from monolinguals in known determinants of QoL, being younger, better educated, and having fewer chronic medical conditions, and had SF-36 scores up to 8 points higher than monolinguals. After adjusting for these differences, bilingualism did not influence scores for any of eight SF-36 scales, whereas questionnaire language influenced scores for four scales. Use of the English SF-36 was associated with higher scores for General Health, Vitality, Role Emotional and Mental Health Scales (odds ratios 1.35-1.41), though the magnitude of these odds ratios suggests this association may not be clinically important. CONCLUSION: Bilingualism did not influence responses to a QoL scale in this large, population-based study of subjects fluent in an alphabet and/or pictogram based language.