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Introduction: Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine the prevalence of hyperuricemia and parameters associated with serum uric acid (SUA) and urine uric acid (UUA) in patients with lymphoma and myeloproliferative neoplasms (MPN). Methods: This cross-sectional study included adult patients with newly diagnosed lymphoma and MPN at the university-based hospital. Clinical characteristics were collected, and independent risk factors for hyperuricemia and hyperuricosuria were determined using multiple logistic regression. Results: One hundred and sixty-five patients were included with a median age of 55 years (45.5-64) and 51.5% were males. There were 91 patients (55.2%) with lymphoma and 74 cases (44.8%) of MPN. Overall, hyperuricemia was prevalent in 43.6% with a median SUA of 6.3 mg/dl (4.6-8) and hyperuricosuria was detected in 39.4% with a median 24-h UUA of 545 mg (365.4-991). Hyperuricemia was observed in patients with lymphoma and MPN in 20.9% and 71.6%, respectively, and hyperuricosuria in 15.4% and 68.9%, respectively. In lymphoma patients, estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 and serum lactate dehydrogenase (LDH) ≥ 250 U/L were associated with hyperuricemia with odds ratio (OR) 3.24, 95% confidence interval (CI) 1.95-11.07, p = 0.006 and OR 2.07, 95%CI 1.62-6.97, p = 0.039), and only elevated serum LDH was related to hyperuricosuria (OR 2.37, 95%CI 1.56-14.29, p = 0.036). In MPN patients, hemoglobin levels <10 g/dl and serum LDH ≥ 640 mg/dl were independent risk factors of hyperuricosuria (OR 1.88, 95%CI 1.42-8.39, p = 0.045 and OR 6.21, 95%CI 1.49-25.74, p = 0.012). Conclusion: Hyperuricemia in patients with hematologic malignancies was common, notably MPN, and parameters associated with hyperuricosuria were provided. In addition to the utilization of allopurinol in patients at high risk of tumor lysis syndrome, patients without hyperuricosuria may also be of significant interest.
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This study aimed to clarify the association of HLA Class I and II with dcSSc and lcSSc in Thais. HLA typing for 11 gene loci (Class I: HLA-A, B and C, and Class II [HLA-DR, DP and DQ]) was carried out using the Next Generation DNA Sequencing method (three fields) in 92 Thai patients with systemic sclerosis (55 dcSSc, 37 lcSSc) and 135 healthy controls (HCs). The distribution of HLA alleles in patients with dcSSc and lcSSc was compared. When compared with HCs, the AF of A*24:02:01, A*24:07:01, B*27:04:01 and B*27:06 showed an increasing trend in lcSSc patients without statistical significance. DRB1*15:02:01, DRB5*01:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01 increased significantly in dcSSc patients. DQB1*05:01:24 and DPB1*13:01:01 also increased significantly in lcSSc patients, but less significantly than in dcSSc patients. The association of DPB1*05:01:01 with lcSSc was significantly protective. HLA-A*24:02:01, B*27:06 and C*03:04:01 formed a three-locus haplotype that also constituted an eight-locus haplotype with DRB1*15:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01. There was a possibility that HLA Class I would play a role in the pathogenesis of lcSSc, while Class II played more of a role in the dcSSc in Thai patients.
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BACKGROUND: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission. METHODS: Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time-to-event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. FINDINGS: 3449 patients were followed up for a median of 2·8 years (IQR 1·1-5·6), totalling 37â662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 0·60 [95% CI 0·51-0·71], p<0·0001; remission: 0·66 [0·57-0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51-0·63], p<0·0001; remission: 0·66 [0·60-0·73], p<0·0001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS. INTERPRETATION: We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission. FUNDING: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.
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Lupus Eritematoso Sistémico , Índice de Severidad de la Enfermedad , Humanos , Femenino , Adulto , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Estudios Longitudinales , Inducción de Remisión , Calidad de VidaRESUMEN
BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.
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Antimaláricos , Azatioprina , Glucocorticoides , Hidroxicloroquina , Inmunosupresores , Lupus Eritematoso Sistémico , Metotrexato , Prednisolona , Nivel de Atención , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Inmunosupresores/uso terapéutico , Hidroxicloroquina/uso terapéutico , Masculino , Glucocorticoides/uso terapéutico , Adulto , Azatioprina/uso terapéutico , Prednisolona/uso terapéutico , Metotrexato/uso terapéutico , Antimaláricos/uso terapéutico , Estudios de Cohortes , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Leflunamida/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Modelos Logísticos , Puntaje de Propensión , Índice de Severidad de la Enfermedad , Tacrolimus/uso terapéutico , Brote de los Síntomas , Resultado del Tratamiento , Antirreumáticos/uso terapéuticoRESUMEN
BACKGROUND/OBJECTIVE: To determine the prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai systemic lupus erythematosus (SLE) patients, and compare them with age- and sex-matched healthy controls (HCs). Associations between thyroid dysfunctions and SLE disease activity, and associated factors for thyroid dysfunctions in SLE also were determined. METHOD: One hundred SLE patients, without apparent clinical thyroid disease, attended the Rheumatology Clinic between November 2021 and October 2022, were enrolled into this study. HCs were matched to SLE cases by age and sex (ratio of 1:1). Clinical manifestations, SLE disease activity and medication received were collected in all SLE patients. Thyroid function tests and thyroid autoantibodies (anti-thyroglobulin: anti-TG and anti-thyroid peroxidase: anti-TPO) were collected from all participants. RESULTS: When compared with HCs, SLE patients had higher prevalence of thyroid dysfunctions, hypothyroidism and euthyroid sick syndrome (28% vs. 7%, p < .001, and 12% vs. 2%, p = .010, and 6% vs. 0%, p = .013, respectively). Prevalence of isolated hypothyroxinemia was higher numerically in SLE patients (9% vs. 3%, p = .074). Prevalence of anti-TG or anti-TPO was no different between SLE patients and HCs (16% vs. 18%, p = .707). There was no association between SLE disease activity and abnormal thyroid functions or thyroid autoantibodies. Family history of thyroid disease and prednisolone use (>10 mg/day) were associated factors for thyroid abnormalities with adjusted OR (95% CI) of 6.13 (1.58-23.75), p = .009 and 4.00 (1.37-11.70), p = .011, respectively. CONCLUSION: Thyroid dysfunctions were more prevalent in SLE patients. Family history of thyroid disease and prednisolone use (>10 mg/day) were independent associated factors of thyroid abnormalities.
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Autoanticuerpos , Lupus Eritematoso Sistémico , Enfermedades de la Tiroides , Humanos , Femenino , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Masculino , Tailandia/epidemiología , Adulto , Autoanticuerpos/sangre , Prevalencia , Persona de Mediana Edad , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/sangre , Estudios de Casos y Controles , Pruebas de Función de la Tiroides , Biomarcadores/sangre , Adulto Joven , Factores de Riesgo , Pueblos del Sudeste AsiáticoRESUMEN
OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).
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Lupus Eritematoso Sistémico , Índice de Severidad de la Enfermedad , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios Longitudinales , Progresión de la Enfermedad , Glucocorticoides/uso terapéutico , Estudios Prospectivos , Adulto JovenRESUMEN
Background: Studies have found that late-onset systemic lupus erythematosus (SLE) patients (age at diagnosis ≥ 50 years) had less severe disease and milder clinical course, but with higher organ damage and mortality rate than early-onset ones (age at diagnosis < 50 years). Unfortunately, direct comparison of renal manifestations and treatment outcomes between late- and early-onset SLE patients has been determined rarely. This study aimed to compare lupus nephritis (LN) manifestations, treatment, and outcomes between late- and early-onset in SLE patients. Methods: Medical records of SLE patients in a lupus cohort at a tertiary care university hospital, seen between January 1994 and June 2020, were reviewed. Late- and early-onset patients were matched with year at SLE diagnosis at a ratio of 1:2 (62 and 124 patients, respectively). Those with LN were identified and analyzed. Results: At SLE onset and end of the study, LN was identified in 29 and 33 late-onset patients, respectively, and 58 and 90 early-onset patients, respectively. At the end of the study, there were 39 and 214 LN flares in late- and early-onset patients, respectively: giving an incident rate (IR) (95% confidence interval (CI))/100 person-years of LN and active LN flares of 2.00 (0.75 - 5.33) vs. 6.11 (4.32 - 8.64), P = 0.020, and 5.78 (2.75 - 12.12) vs. 18.28 (13.93 - 24.00), P = 0.001, respectively. Late-onset patients received a higher proportion of moderate- to high-dose corticosteroids, but fewer immunosuppressive drugs. In all LN flares, no difference existed between the two groups in serum creatinine, degree of proteinuria, and proportion of patients with nephrotic range proteinuria or rapidly progressive glomerulonephritis, and outcomes in terms of complete, partial or no-remission were similar between them. Mortality rate was higher in late-onset patients (27.27% vs. 6.67%, P = 0.004). Conclusion: This matched controlled study of year at SLE diagnosis showed that late-onset SLE patients had lower prevalence of LN and LN flares. Although they received fewer immunosuppressive drugs, their renal manifestations and treatment outcomes were no different from those in early-onset patients.
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OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred. RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day. CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.
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Glucocorticoides , Lupus Eritematoso Sistémico , Prednisolona , Brote de los Síntomas , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Femenino , Masculino , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Adulto , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Reducción Gradual de Medicamentos/métodos , Estudios Longitudinales , Progresión de la Enfermedad , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.
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Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Humanos , ADN , Recolección de Datos , Pruebas HematológicasRESUMEN
INTRODUCTION: This study aimed to compare the efficacy of non-loading versus loading low-dose colchicine in patients with acute crystal-associated arthritis. MATERIALS AND METHODS: All in-patients who were admitted to Chiang Mai University Hospital with non-arthritis disease and developed acute crystal-associated arthritis during admission (within 48 h after arthritis onset) were invited to join this study. The patients were randomized into two groups. Patients in Group I (non-loading group) and Group II (loading group) received colchicine at 1.2 and 2.4 mg in the first 24 h, respectively. The primary outcome was the patients' pain response at 24 h after treatment. RESULTS: Of 80 patients, 49 were acute gouty arthritis, and 31 acute calcium pyrophosphate (CPP) arthritis. The mean [95% CI] pain score was no different between Groups I and II at the baseline level (6.46[5.72-7.19] vs. 6.654[5.85-7.44], p = .867) and at 24 h (3.13[2.43-3.82] vs. 3.18[2.42-3.93], p = .907). The proportion of patients with ≥50% pain reduction was not different (57.50% vs. 55.00%, p = .822). Sensitivity analysis among patients with a baseline pain score of ≥4 showed the same pattern of response. Mild diarrhea was common and comparable in both groups. Subgroup analysis according to renal function (eGFR < 60 vs. ≥60 mL/min/1.73 m2 ) or type of crystals (acute gouty arthritis vs. acute CPP arthritis) also showed the same pattern of response. CONCLUSION: Non-loading low-dose colchicine was as effective as loading low-dose colchicine in patients with acute crystal-associated arthritis, regardless of renal function or type of crystals.
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Artritis Gotosa , Colchicina , Humanos , Artritis Gotosa/diagnóstico , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/inducido químicamente , Colchicina/efectos adversos , Dolor/inducido químicamente , Proyectos de Investigación , Método Doble CiegoRESUMEN
Background: The infliximab biosimilar CT-P13 was approved in Thailand in 2015. Methods: This open-label, multicenter, post-marketing surveillance study evaluated the safety (events of special interest [ESIs]; primary end point) and effectiveness of 46 weeks of CT-P13 treatment according to routine practice in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA), with 1 year follow-up post-treatment. Results: 30 patients were enrolled (16 RA, 8 AS and 6 PsA). Infections were the most frequently reported study drug-related ESIs (2 RA and 2 AS). One patient with RA and one with PsA experienced infusion-related reactions. No cases of tuberculosis, malignancy (as expected, given 1 year follow-up), or drug-induced liver disease were reported. Disease activity improved across indications. Conclusion: CT-P13 was well tolerated and effective across indications.
Infliximab is one biological medicine used to treat inflammatory diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). CT-P13 is a near-identical copy, called a biosimilar, of the original ('reference') version of infliximab. CT-P13 is the first biosimilar to receive regulatory approval for treatment of the same three diseases from the European Medicines Agency (EMA) and US Food and Drug Administration. Biosimilarity means that CT-P13 does not differ from the original version of infliximab in clinically important ways, such as how safe it is and how well it works. CT-P13 and reference infliximab provided similar symptom relief during previous clinical trials, and both drugs caused similar side effects. It is important to monitor the safety and performance of CT-P13 when given during routine clinical practice, and in different ethnic populations, such as through the study reported here. Following regulatory approval in Thailand, 30 patients prescribed CT-P13 during routine clinical practice participated in this study. The study included 16 patients with RA, eight with AS and six with PsA. The patients took CT-P13 for 46 weeks and were monitored for a further year. Side effects of CT-P13 were as expected based on previous experience and did not raise any safety concerns. Based on the known safety profile of CT-P13, the study looked at some side effects in particular: infections were the most common of these side effects, experienced by 16 patients overall (seven patients with RA, five patients with AS and four patients with PsA). CT-P13 improved symptoms for all of the diseases. The study suggests that CT-P13 can be given safely and reduces symptoms in Thai patients with AS, RA or PsA. Thai Clinical Trials Registry: TCTR20170817005 (www.thaiclinicaltrials.org/show/TCTR20170817005).
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Artritis Psoriásica , Artritis Reumatoide , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/tratamiento farmacológico , Tailandia , Artritis Reumatoide/tratamiento farmacológico , Espondilitis Anquilosante/tratamiento farmacológico , Vigilancia de Productos ComercializadosRESUMEN
Rheumatoid arthritis (RA) is an involving chronic systemic inflammatory disease which mainly affects the joints. Several factors including genetic, environment and infections have been acknowledged as being involved in the pathogenesis and aggravation of RA. Air pollution, particularly particulate matter is widely recognized as a cause of health problems. This review is to summarize and discuss the association between air pollutants and the development or the aggravation of RA based on evidence from in vitro, in vivo and clinical studies. The results from the review found that air pollutants can stimulate immunological processes and stimulate inflammatory mediators and autoantibodies productions, both in intro and in vivo studies. In addition, air pollutants can induce RA and aggravate RA disease activity. Unfortunately, there also are some discrepancies in the results, which might be due to the type cell line and the concentration of air pollutants used in the in vitro and in vivo studies, as well as the concentration and duration of exposure in human studies. These findings suggest that future studies focused on elucidating these mechanisms using advanced techniques and identifying reliable biomarkers to assess individual susceptibility and disease activity should be carried out. Longitudinal studies, intervention strategies, and policy implications also should be explored. A comprehensive understanding on these association will facilitate targeted approaches for prevention and management of air pollutant-induced RA and improve health outcome.
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Contaminantes Atmosféricos , Contaminación del Aire , Artritis Reumatoide , Humanos , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Artritis Reumatoide/genética , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Material Particulado/toxicidad , Material Particulado/análisis , Estudios LongitudinalesRESUMEN
BACKGROUND: Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). METHODS: The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. RESULTS: The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). CONCLUSIONS: In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.
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Artritis , Lupus Eritematoso Sistémico , Nefritis , Humanos , Persona de Mediana Edad , Edad de Inicio , Lupus Eritematoso Sistémico/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Nefritis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Cardiac wall rupture (CWR) is a serious and often fatal complication of myocardial infarction (MI). Despite an increase in the incidence of MI in patients with systemic lupus erythematosus (SLE), cases of CWR in these patients have been reported rarely. This study reports an SLE patient with CWR and pseudoaneurysm formation and reviews previously reported cases of CWR in SLE patients. An English language literature review of from the PubMed, EMBASE, and Scopus databases on published cases of CWR in SLE, up until January 2023, was performed and analyzed. The search identified 4 patients, including the present one, 5 cases altogether. All of them were female aged 27-40 years, and 3 of them had had SLE for 10 years or more. Chest pain and dyspnea were the common presentations. All had left ventricular (LV) wall rupture. Three patients had LV wall rupture with pseudoaneurysm formation (one had MI with normal coronary artery, one myocardial necrosis secondary from small coronary artery vasculitis and one MI from uncertain cause). The other 2 patients had LV free wall rupture (one had MI with extensive coronary atherosclerosis with coronary arteritis, and the other septic myocarditis with septic coronary arteritis) and these 2 patients died before the diagnosis was made. Three patients with pseudoaneurysm received surgical correction with good clinical outcomes in all. Cardiac wall rupture is a serious and often fatal cardiac complication. Emergency diagnosis and appropriate management with an experienced cardiology team is crucial. Surgical correction is the treatment of choice. Key Points ⢠Cardiac wall rupture, a serious and often fatal cardiac complication, has rarely been described in SLE patients. ⢠Emergency diagnosis and appropriate management with an experienced cardiology team is crucial. Surgical correction is the treatment of choice.
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Aneurisma Falso , Arteritis , Enfermedad de la Arteria Coronaria , Cardiopatías , Lupus Eritematoso Sistémico , Infarto del Miocardio , Humanos , Femenino , Masculino , Aneurisma Falso/complicaciones , Aneurisma Falso/diagnóstico por imagen , Infarto del Miocardio/complicaciones , Enfermedad de la Arteria Coronaria/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Arteritis/complicacionesRESUMEN
OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up. METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied. RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P < 0.05 for damage accrual ORs at all time points). CONCLUSION: In SLE patients with active disease receiving standard of care, mSRI attainment predicts favorable outcomes over long-term follow-up, supporting the clinical meaningfulness of SRI attainment as an SLE trial end point.
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Lupus Eritematoso Sistémico , Humanos , Estudios Prospectivos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisolona/uso terapéutico , Glucocorticoides/uso terapéutico , Oportunidad RelativaRESUMEN
OBJECTIVES: This study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: A decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed. RESULTS: All 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor. CONCLUSIONS: At the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.
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Antirreumáticos , Artritis Psoriásica , Biosimilares Farmacéuticos , Humanos , Infliximab/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Análisis Costo-Beneficio , Tailandia , Antirreumáticos/uso terapéuticoRESUMEN
BACKGROUND: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. METHODS: This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. FINDINGS: Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. INTERPRETATION: Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. FUNDING: AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.
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Corticoesteroides , Lupus Eritematoso Sistémico , Adulto , Humanos , Femenino , Masculino , Estudios de Cohortes , Corticoesteroides/uso terapéutico , Prednisolona , Lupus Eritematoso Sistémico/tratamiento farmacológico , Terapia de InmunosupresiónRESUMEN
Abstract Background Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). Methods The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. Results The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). Conclusions In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.
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HLA studies in patients with systemic sclerosis (SSc) have shown variable results. This study aimed to examine the association of HLA class I and II risk alleles in Thai SSc patients, and clarify the contribution of risk HLA alleles to the pathogenesis and clinical manifestations. Blood samples from 92 SSc patients and 135 healthy controls (HCs) were collected. Eleven loci of the HLA class I (HLA-A, B, and C) and class II (HLA-DR, DP, and DQ) genes were determined by a 3-field (6-digit) analysis using the Next Generation DNA Sequencing (NGS) method. Anti-topoisomerase-I antibodies (ATA) and anti-centromere antibodies (ACA) were identified by ELISA methods. Allele frequencies (AFs) of HLA-DRB1*15:02:01, DRB5*01:02:01, DQB1*05:01:24, DPB1*13:01:01, and DQA1*01:01:01 were increased significantly in the whole SSc and SSc patients with positive ATA, but with negative ACA (SSc/ATA+/ACA-). Of these, DPB1*13:01:01 was the most susceptible allele. The DRB1*15:02:01, DQB1:05:01:24, and DPB1*13:01:01 alleles were estimated to locate on the unique haplotype, and haplotype frequency was estimated to be significantly higher than those in the HCs (p = 0.002). The linkage analysis of DRB1*15/16 revealed that most of the DRB1*15:02:01 alleles were linked to DRB5*01:02:01 or DRB5*01:08:01N. The linkage of DRB1*16:02:01 to DRB5*01:01:01 was observed frequently. The associations of risk alleles with several SSc clinical features were observed. HLA-DRB1*15:02:01, DRB5*01:02:01, DQB1*05:01:24, and DPB1*13:01:01 on the unique haplotype were associated with the pathogenesis and clinical features of SSc in Thai patients. The linkage of DRB1*15:02:01 to DRB5*01:08:01N was observed commonly in northern Thai patients.