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.

The management of anti-neutrophil cytoplasmic antibody-associated vasculitis: what has changed in the last 10 years?

The management of anti-neutrophil cytoplasmic antibody-associated vasculitis has substantially improved in the last decade. For the induction of remission, rituximab is increasingly used in place of cyclophosphamide, particularly for patients with proteinase 3 (PR3)-associated vasculitis or relapsing disease, and those wishing to preserve their fertility. A lower dose regimen of glucocorticoids, with a more rapidly tapering schedule, is preferable and is as effective and safer than the standard-dose regimen. Avacopan, the complement C5a receptor inhibitor, is effective in the treatment of associated vasculitis and may replace glucocorticoids in the future. Plasma exchange provides no additional benefit for patients with severe anti-neutrophil cytoplasmic antibody-associated vasculitis, although it is still used in selected patients on a case-by-case basis. Rituximab is preferred for the maintenance of remission, repeated at fixed time intervals. The duration for which immunosuppressive therapy should be given is uncertain, but is generally longer for patients with PR3 disease or persistent anti-neutrophil cytoplasmic antibody positivity. The anti-interleukin 5 monoclonal antibody, mepolizumab, is effective for the treatment of non-severe eosinophilic granulomatosis with polyangiitis. Several other targeted therapies are in the pipeline and further progress is expected in the coming years.

Effect of a Real-Time Risk Score on 30-day Readmission Reduction in Singapore.

OBJECTIVE: To develop a risk score for the real-time prediction of readmissions for patients using patient specific information captured in electronic medical records (EMR) in Singapore to enable the prospective identification of high-risk patients for enrolment in timely interventions. METHODS: Machine-learning models were built to estimate the probability of a patient being readmitted within 30 days of discharge. EMR of 25,472 patients discharged from the medicine department at Ng Teng Fong General Hospital between January 2016 and December 2016 were extracted retrospectively for training and internal validation of the models. We developed and implemented a real-time 30-day readmission risk score generation in the EMR system, which enabled the flagging of high-risk patients to care providers in the hospital. Based on the daily high-risk patient list, the various interfaces and flow sheets in the EMR were configured according to the information needs of the various stakeholders such as the inpatient medical, nursing, case management, emergency department, and postdischarge care teams. RESULTS: Overall, the machine-learning models achieved good performance with area under the receiver operating characteristic ranging from 0.77 to 0.81. The models were used to proactively identify and attend to patients who are at risk of readmission before an actual readmission occurs. This approach successfully reduced the 30-day readmission rate for patients admitted to the medicine department from 11.7% in 2017 to 10.1% in 2019 (p < 0.01) after risk adjustment. CONCLUSION: Machine-learning models can be deployed in the EMR system to provide real-time forecasts for a more comprehensive outlook in the aspects of decision-making and care provision.

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.

Laboratory tests in rheumatology: A rational approach.

Laboratory tests are useful in diagnosing rheumatic diseases, but clinicians should be aware of the limitations of these tests. This article uses case vignettes to provide practical and evidence-based guidance on requesting and interpreting selected tests, including rheumatoid factor, anticitrullinated peptide antibody, antinuclear antibody, antiphospholipid antibodies, antineutrophil cytoplasmic antibody, and human leukocyte antigen-B27.

The patient with Acute Thrombocytopenia.

A wide variety of conditions can present with acute thrombocytopenia, ranging from those that are relatively benign and self-limiting to those that require urgent therapeutic intervention. Initial decision-making relies on a good history and the results of some simple investigations. Although a precise diagnosis of the underlying cause might often not be possible in the acute setting, supportive treatments should be provided to all patients. This article describes a practical approach to the diagnosis and initial management of patients presenting with acute thrombocytopenia, with the aid of a case vignette.

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.

How to diagnose fibromyalgia.

This review discusses the basic pathophysiological mechanisms that are necessary to understand the principles of diagnosis and management of fibromyalgia, and outlines a practical diagnostic approach to patients presenting with chronic widespread pain.

Denosumab: a novel antiresorptive drug for osteoporosis.

Denosumab is a novel antiresorptive drug that has been approved for use as a first-line drug for primary and secondary prevention of osteoporotic fractures. The authors discuss the mechanism of action of denosumab, review the evidence for its efficacy and safety in patients with osteoporosis, and offer recommendations for its use in clinical practice.

Problem based review: the patient with recent onset polyarthritis.

A wide variety of conditions can present as acute polyarthritis, ranging from those that are potentially life threatening, to those that are self-limiting, and those that represent the early stages of a persistent and potentially destructive form of arthritis. In this article, we describe the diagnostic approach and initial management of patients with recent onset polyarthritis, with the aid of an illustrative case vignette.

Safety issues with bisphosphonate therapy for osteoporosis.

Randomized controlled trials have demonstrated the efficacy of bisphosphonates (BP) in improving BMD and reducing fracture risk. Various safety issues that were not noted in clinical trials have, however, now emerged with post-marketing surveillance and increasing clinical experience. The risk of atypical femoral fracture could increase with long-term use of BP, although absolute risk is very small, particularly when balanced against benefits. A drug holiday should be considered after 5 years of treatment for patients at low risk of fracture, although there is no official recommendation regarding this to guide clinicians. Osteonecrosis of the jaw from low-dose BP used for osteoporosis is very rare, and mainly a complication with high-dose i.v. BP used in oncology. The risk of atrial fibrillation too is negligible, and a definite link cannot be established between BP and oesophageal cancer. BP should be avoided in patients with severe renal impairment and during pregnancy and lactation because of limited safety data. Further epidemiological and clinical data are required to establish safety of BP in long-term users (>5 years) and provide evidence-based management.

Problem based review: The patient with acute monoarthritis.

Acute monoarthritis is a common medical emergency with wide differential diagnosis. Common underlying causes include trauma, septic arthritis, crystal induced arthritis (gout and pseudogout), and reactive arthritis. Of these, septic arthritis is the diagnosis not to miss because of its association with significant morbidity and mortality. Precise diagnosis of the underlying cause of monoarthritis relies on a good history, physical examination findings, and results of focussed investigations. In this article, a practical approach to diagnosis and initial management of patients presenting with acute monoarthritis is described with the aid of a case vignette.

Proximal myopathy: diagnostic approach and initial management.

Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections and sarcoidosis. Clinical assessment should aim to distinguish proximal myopathy from other conditions that can present similarly, identify patients who need prompt attention, like those with cardiac, respiratory or pharyngeal muscle involvement, and determine underlying cause of myopathy. Initial evaluation should include simple tests, like creatine kinase, thyroid function and (25)OH vitamin D levels, but further evaluation including neurophysiological studies, muscle imaging and muscle biopsy should be considered for patients in whom no toxic, metabolic or endocrine cause is found, and in those with clinical features suggestive of inflammatory or hereditary myopathy. Additionally, screening for malignancy and testing for anti-Jo1 antibody is indicated for selected patients with IIM. Management depends on underlying cause, and includes measures, such as removal of offending agent, correction of endocrine or metabolic problem, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation and genetic counselling for muscular dystrophies.

Recent advances in rheumatoid arthritis.

Management of rheumatoid arthritis (RA) has radically changed over the last decade. Diagnostic methods have improved with availability of highly specific tests such as antibody to cyclic citrullinated peptide (specificity approximately 96%), and introduction of advanced imaging modalities such as ultrasound and magnetic resonance imaging to facilitate earlier diagnosis. The current aim of management is to achieve remission and prevent joint damage. In order to achieve this goal, inflammation is suppressed as much as possible during the early phase of the disease before onset of joint damage. Aggressive treatments with combinations of disease modifying anti-rheumatic drugs are commenced earlier in the course of disease, and tight control maintained with regular objective monitoring of disease activity. Early use of anti-TNFalpha (tumour necrosis factor alpha) therapy in combination with methotrexate helps to achieve better clinical and radiographic outcomes, which can be maintained for up to 5 years after withdrawal of anti-TNFalpha therapy. Apart from anti-TNFalpha, several other biological treatments are now available, including those that target CD20 on B cells (rituximab), cytokines such as IL1 (anakinra) and IL6 (tocilizumab), and molecules that cause interaction between antigen presenting cells and T cells (abatacept). There is better awareness and understanding of RA associated complications such as cardiovascular disease and osteoporosis. Use of non-steroidal anti-inflammatory drugs is on the decline in light of recent concerns about cardiovascular safety. Evidence is emerging in support of statins and bisphosphonates for improving RA disease activity and preventing erosions, respectively. In the coming years, further improvements in therapeutic strategies are likely with the pace at which research is currently progressing.

Systemic lupus erythematosus: diagnosis for the non-specialist.

This review discusses the pitfalls in placing too much reliance on an antinuclear antibody test result for the diagnosis of systemic lupus erythematosus, outlines a practical approach to patients in whom this illness is suspected, and gives guidance on how to request these tests sensibly.

Acute pancreatitis with pseudocyst formation in a patient with polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a term that includes patients with necrotizing inflammation of medium sized arteries, and excludes those with microscopic vessel involvement. Its manifestations are protean and include constitutional symptoms such as fever, malaise, weight loss, myalgia, peripheral neuropathy, rash, and gut and renal involvement. Although gastrointestinal manifestations have been noted in up to a third of patients with PAN, clinical presentation with pancreatic involvement has been reported only rarely. We describe a patient with PAN who developed acute pancreatitis with pseudocyst formation as well as infarcts in the spleen and liver.

How valuable is screening for thyroid disease in patients with carpal tunnel syndrome?

BACKGROUND: It has been suggested that many patients with carpal tunnel syndrome have associated thyroid or other metabolic diseases. METHODS: 206 patients with clinical features suggestive of carpal tunnel syndrome (CTS), including those with known underlying cause of CTS, were screened for thyroid dysfunction. Nerve conduction studies were compatible with a diagnosis of CTS in 136 patients (CTS group). RESULTS: We diagnosed only 2 new cases of hypothyroidism (1.5% of patients in the CTS group) and none with hyperthyroidism. CONCLUSIONS: Thus routine screening of patients with isolated CTS for thyroid function abnormality does not appear to be worthwhile.