Recurrent Stent Thrombosis Secondary to Immunoglobulin G4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is an insidiously progressive multiorgan disease. However, lack of familiarity with IgG4-RD results in patients often being undiagnosed and undertreated. IgG4-RD can affect any organ, and manifests as aortitis within the cardiovascular system. Cardiac involvement is less common, and myocardial infarction is rarely reported. We report the first case of a patient with multiple myocardial infarctions caused by recurrent stent thrombosis associated with IgG4-RD, which resolved upon treatment of IgG4-RD. This case highlights the importance for cardiologists to consider IgG4-RD as a rare but possible association with stent thrombosis.

Mortality and hospitalization outcomes of interstitial lung disease and pulmonary hypertension in the Singapore systemic sclerosis cohort.

OBJECTIVES: We compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement]. METHODS: In the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity <70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival. RESULTS: Of 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05-6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60-5.76) and ILD (HR 1.84, 95% CI: 1.04-3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13-5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups. CONCLUSION: PAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

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.

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.

A double-blind randomized placebo-controlled trial of probiotics in systemic sclerosis associated gastrointestinal disease.

OBJECTIVE: Assess whether treatment with probiotics improve gastrointestinal symptoms in patients with systemic sclerosis (SSc). METHODS: In this double-blind randomized placebo-controlled parallel-group phase II trial, SSc subjects with total score ≥ 0.1 on a validated SSc-specific gastrointestinal tract (GIT) questionnaire were randomized (1:1) to receive 60 days of high dose multi-strain probiotics (Vivomixx® 1800 billion units/day) or identical placebo, followed by an additional 60 days of probiotics in both groups. Between group differences in GIT score change were assessed after 60 days (primary outcome, time-point T1) and 120 days (secondary outcome, time-point, T2) by an intention-to-treat approach. Stool samples at three time-points were subjected to 16S next generation sequencing. RESULTS: Forty subjects were randomized to placebo-probiotics (n = 21) or probiotics-probiotics (n = 19). At T1, no significant improvement was observed between the two groups, reported as mean ± SE for total GIT score (placebo 0.14 ± 0.06 versus probiotics 0.13 ± 0.07; p = 0.85) or its subdomains. At T2, whilst there was no significant improvement in total GIT score (placebo-probiotics -0.05±0.06; probiotics-probiotics -0.18 ± 0.07; p = 0.14), there was significant improvement of GIT-reflux in the probiotic group (-0.22 ± 0.05 versus placebo-probiotics 0.05 ± 0.07; p = 0.004). Subjects on probiotics exhibited increasing stool microbiota alpha diversity compared to the placebo-probiotics group. Adverse events (AEs) were mild, with similar proportion of subjects with AEs and serious AEs in both groups. CONCLUSION: Whilst there was no clear improvement in overall GI symptoms after 60 days, we observed significantly improved GI reflux after 120 days of probiotics. The trial confirmed safety of multi-strain probiotics in SSc patients. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01804959.

Cost-effectiveness of an adherence-enhancing intervention for gout based on real-world data.

AIM: Medication non-adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout; however, non-adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008-2010, an adherence-enhancing program was implemented at the rheumatology division of a public tertiary hospital. The cost-effectiveness of this program has not been fully evaluated. With healthcare resources being finite, the value of investing in adherence-enhancing interventions should be ascertained. This study aims to evaluate the cost-effectiveness of this adherence-enhancing program to inform optimal resource allocation toward better gout management. METHOD: Adopting a real-world data approach, we utilized patient clinical and financial records generated in their course of routine care. Intervention and control groups were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and effect data were followed through 1-2 years. A decision tree was developed in TreeAge using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty. RESULTS: At an assumed willingness-to-pay threshold of $50 000 USD ($70 000 SGD) per quality-adjusted life year (QALY), the intervention had an 85% probability of being cost-effective compared to routine care. The incremental cost-effectiveness ratio was $12 866 USD per QALY for the base case and ranged from $4 139 to $21 593 USD per QALY in sensitivity analyses. CONCLUSION: The intervention is cost-effective in the short-term, although its long-term cost-effectiveness remains to be evaluated.