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.

A systematic review of the association of obesity with the outcomes of inflammatory rheumatic diseases.

This was a systematic review of the literature on the association between obesity and the outcome of inflammatory rheumatic diseases. We conducted a literature search using PubMed®, Embase and PsycINFO®. Articles were classified into three categories based on the effects of obesity on the outcomes of inflammatory rheumatic diseases. The subject population, country, type of studies, number of patients, measurement of obesity and outcomes assessed were presented. Quality was appraised using Kmet et al's criteria. 4,331 articles were screened and 60 were relevant to the objective. Obesity had a negative, positive and neutral association with outcomes of inflammatory rheumatic diseases in 38 (63.3%) studies with 57,612 subjects, 11 (18.3%) studies with 3,866 subjects, and 11 (18.3%) studies with 3,834 subjects, respectively. In most studies, the disease population had been diagnosed with rheumatoid arthritis (RA). Tumour necrosis factor-α inhibitors were mostly associated with negative outcomes. More studies examining subjects outside Europe and North America and diseases other than RA are warranted.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

A qualitative study of quality of life domains and subdomains relevant to patients with spondyloarthritis.

AIMS: To identify quality of life (QoL) domains and subdomains relevant to patients with different spondyloarthritis (SpA) subtypes in Singapore, and to assess how identified QoL domains and subdomains map onto currently used patient-reported outcome measures (PROMs). METHODS: Nine focus group discussions (FGDs), including two previously conducted FGDs from the Updating the Psoriatic Arthritis Core Domain Set Study, were conducted with patients with SpA in Singapore. The FGDs were organized by SpA subtype and language spoken. All FGDs were audio-taped, transcribed verbatim. After thematic analysis through open and axial coding, the domains were organized using the World Health Organization Quality of Life (WHOQOL) framework. Identified QoL domains and subdomains were mapped to currently used PROMs. RESULTS: The nine FGDs included 51 patients. In total, 27 domains and 92 subdomains were identified and then organized within the 7 broad categories of the WHOQOL framework. Patients in Singapore were more concerned about "financial resources, " "work satisfaction" and "positive feelings" while less concerned about "freedom, physical safety and security" than patients in Western countries. "Home environment" and "work satisfaction" emerged as unique QoL domains relevant to patients with axial SpA (axSpA). PROMs for psoriatic arthritis (PsA) can capture both identified domains of PsA and axSpA. CONCLUSIONS: A wide range of QoL domains and subdomains are relevant to SpA patients in Singapore, and there appears to be minimal differences in their relative importance between SpA subtypes. This study supports the development and validation of common QoL-specific PROMs for usage in SpA.

Tailoring of recommendations to reduce serious cutaneous adverse drug reactions: a pharmacogenomics approach.

The Health Sciences Authority launched a pharmacogenetics initiative in 2008 to facilitate evaluation of pharmacogenetics associations pertinent for Chinese, Malays and Indians in Singapore. The aim was to reduce the incidence and unpredictability of serious adverse drug reactions, with a focus on serious skin adverse drug reactions. This paper describes the gathering of evidence and weighing of factors that led to different genotyping recommendations for HLA-B*15:02 with carbamazepine and HLA-B*58:01 with allopurinol, despite both having strong genetic associations. Translation of pharmacogenomics at a national level requires careful deliberation of the prevalence of at-risk allele, strength of genetic associations, positive predictive value, cost-effectiveness and availability of alternative therapies. Our experience provides a perspective on translating genomic discoveries in advancing drug safety.

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.

Effect of ethnicity on disease activity and physical function in psoriatic arthritis in a multiethnic Asian population.

Geographic differences in manifestation of psoriatic arthritis (PsA) could be related to differences in genetic or environmental factors. We aimed to compare the disease activity and functional status using validated outcome measures among patients with PsA of different ethnicities living in the same environment. We performed a cross-sectional study on consecutive patients with PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria from a single center. Sociodemographic data, clinical variables, and patient-reported outcomes were collected using a standardized protocol. Disease activities were assessed by validated composite scores: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), Composite Psoriatic Disease Activity Index (CPDAI), and minimal disease activity (MDA). Physical function was assessed with Health Assessment Questionnaire (HAQ) and the Medical Outcome Study Short-Form 36 (SF36) physical function subscales. Linear regression analyses were performed to identify variables associated with disease activities and physical function. Ninety-eight patients (51.5%, men) with mean (±SD) age and duration of PsA of 51.5 ± 13.8 and 5.5 ± 8.4 years were recruited. Indian was overrepresented compared with the national distribution of ethnicities. Compared to Chinese, Indian patients were more likely to be using biological therapies, have higher tender joint count, and worse enthesitis. Higher proportion of Indians had higher disease activity categories measured by cDAPSA, CPDAI, and MDA and had poorer physical function. In the multivariable analysis, ethnicity was significantly associated with HAQ and SF36-PF. Compared to Chinese, Indians with PsA living in the same environment had worse disease activity and physical function measured by validated outcomes.

Relapsing polychondritis in Singapore: a case series and review of literature.

INTRODUCTION: This study aimed to describe the clinical presentation, treatment and outcome of patients with relapsing polychondritis (RP) who were seen at a large tertiary-care academic medical institution in Singapore. METHODS: The medical records of all patients diagnosed with RP at the Department of Rheumatology and Immunology, Singapore General Hospital, Singapore, between 2005 and 2013 were reviewed. The diagnosis of RP was made using the modified McAdam criteria. RESULTS: Ten patients were diagnosed with RP during the study period. Among these patients, five fulfilled the modified McAdam criteria and five were probable cases of RP. The most common clinical presentations were auricular chondritis (n = 9), episcleritis or scleritis (n = 5), and large airway involvement (n = 3). All of the patients received prednisolone. Five patients developed haematological disorders. Patients with both RP and haematological disorders had a longer duration of RP symptoms prior to diagnosis, compared to patients with RP who did not develop haematological disorders (average duration of symptoms 14.7 months vs. 4.2 months). CONCLUSION: The high frequency of patients with haematological malignancies in this series was unexpected. Myelodysplastic syndrome has been reported, but other haematological malignancies are rarely associated with RP. As the association between haematological malignancies and RP is currently unclear, the threshold for haematological/lymphoproliferative screening should be lowered in patients with RP.

A rare cause of reversible unilateral third nerve palsy.

CASE REPORT: A 59-year-old Chinese male presented in January 2007 with acute left retro-orbital headache, diplopia and left partial ptosis. Isolated left third nerve palsy was diagnosed. Imaging studies and cerebral angiography excluded a posterior communicating artery aneurysm. Anti-nuclear (titre 1/800, speckled pattern), anti-PR3, anti-Ro and anti-La antibodies were present. Sjogren's syndrome (SS) was considered in view of positive anti-Ro and La antibodies, and was confirmed with focal lymphocytic infiltrates on labial salivary gland biopsy and a positive Schirmer's test (6 mm of tear flow over 5 min). Immunosuppressive therapy was started 2 months after his initial presentation and within 2 weeks, the patient experienced an almost complete recovery of both ptosis and diplopia. He has been on tapering doses of prednisolone since and his condition remains stable. CONCLUSION: This patient has cranial neuropathy secondary to Sjogren's syndrome. The rapid reversibility of the oculomotor nerve palsy with immunosuppression suggests lymphocytic infiltration or autoantibodies as the cause rather than a vasculitic process, which would have led to irreversible or slowly, partially reversible ischaemic damage.