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1.
Rheumatology (Oxford) ; 59(2): 281-291, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302695

RESUMO

OBJECTIVE: This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual. METHODS: In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period. RESULTS: A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual. CONCLUSION: Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).

2.
Clin Rheumatol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691040

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from both disease and medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during their prime productive years resulting in substantial economic burden on the patient, caregivers, and society due to direct, indirect, and intangible costs. This illness burden is compounded in developing countries with limited resources due to various disparities in healthcare delivery. Physician education and practical referral and endorsement guidelines adapted to the local setting reinforce continuity and coordinated care. Likewise, patient education, self-help programs, and shared decision-making are essential best practice in the clinics. Both physician education and patient education improve overall outcomes in chronic diseases like SLE. As a developing country with very few rheumatologists and/or lupus specialists, efficient healthcare delivery for most Filipino lupus patients remains elusive. We describe our experience in confronting these challenges through development of strategies which focus on physician and patient education. KEY POINTS: • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable course, requiring specialized, individualized, and coordinated care by a healthcare team. • Health disparities and limited resources significantly contribute to illness burden on the patient, family, and society. • Physician education on SLE must commence at undergraduate medical school, be integrated in Internal Medicine and Pediatrics, and reinforced through specialized training in Rheumatology and related specialties. • Patient education and empowerment are integral to improving healthcare outcomes especially in a resource-limited setting.

3.
Int J Rheum Dis ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692250

RESUMO

AIM: To identify clinical risk factors associated with herpes zoster (HZ) infections in systemic lupus erythematosus (SLE). METHODS: A case-control study of HZ infection was performed in SLE patients seen at the University of Santo Tomas Lupus Clinics from 2009-2014. Cases were matched 1:2 to SLE controls without HZ infection for age, sex, and disease duration. Clinical characteristics, SLE disease activity, and immunosuppressive use were compared. RESULTS: Sixty-five SLE patients (61, 93.8% female) who developed HZ were matched with 130 SLE patients without HZ. Mean age was 36.75 years (±1.35; P = 1.00) for the case group; mean SLE disease duration at first HZ infection was 6.1 years (±3.3; P = .919). Four patients had more than 1 episode of HZ. There was localized HZ in 63/65 (97%), and 2 (3%) disseminated HZ infections. The case group received higher doses of prednisone 64/65 (P = .012), mean prednisone dose 18.62 mg/d (±1.48, P < .001) and more were exposed to cyclophosphamide (Cyc) (19/65; P < .001) compared to the control group's mean prednisone dose of 11.73 mg/d (±1.16); there was Cyc use in 7/130 patients. Cyc in addition to mycophenolate mofetil (MMF) use among lupus nephritis patients conferred the highest risk for HZ infection occurrence. Hydroxychloroquine (HCQ) use reduced the risk for HZ by 87% (adjusted odds ratio 0.13, P = .003). CONCLUSION: Immunosuppressives and corticosteroid use are risk factors associated with the development of HZ in SLE. The risk for HZ increases among patients given intravenous Cyc and MMF for lupus nephritis. SLE disease activity did not show a direct association with HZ occurrence. HCQ use appeared to have a protective role against HZ infection.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31586420

RESUMO

OBJECTIVE: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study. METHODS: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random slope) at weeks 24 and 52, and observed data at week 52. Assessments at week 52 included additional efficacy endpoints (non-responders imputation and mixed-effects models for repeated measures) and safety. RESULTS: The majority (86.6%) of patients completed 52 weeks of treatment. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS ⩽0.5) was 91.8, 85.2 and 87.2% in 300, 150 and 150 mg no load groups, respectively, at week 52. The change in vdH-mTSS from baseline to week 52 using random slope [mean change (s.e.)] was -0.18 (0.17), 0.11 (0.18) and -0.20 (0.18) in 300, 150 and 150 mg no load groups, respectively; the corresponding observed data [mean change (s.d.)] was -0.09 (1.02), 0.13 (1.39) and 0.21 (1.15). Clinical efficacy endpoints were sustained, and no new or unexpected safety signals were reported through 52 weeks. CONCLUSION: Secukinumab 300 and 150 mg with or without s.c. loading regimen provided sustained low rates of radiographic progression through 52 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02404350.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31560454

RESUMO

A project towards new SLE classification criteria supported by both EULAR and the ACR is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which would argue against independently counting these items. However, these interrelationships have not been formally investigated. OBJECTIVES: To evaluate the interrelationship between candidate criteria items in an international early SLE cohort and in the Euro-Lupus cohort. METHODS: The international early SLE cohort included 389 patients, who were diagnosed within the last 3 years. Data on ACR 1997, SLICC 2012 and 30 additional items were collected. To evaluate the inter-relationship of criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations of the same organ-system. The correlations identified in the international early SLE cohort were validated in the Euro-Lupus cohort. RESULTS: A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti-Sm and anti-dsDNA and anti-RNP, anti-Ro with anti-La, and between anti-phospholipid antibodies), and these results were validated in the Euro-Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation. CONCLUSIONS: Some of the candidate SLE criteria do cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important for the structure of new SLE classification criteria.

6.
Int J Rheum Dis ; 22(10): 1933-1936, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31424178

RESUMO

INTRODUCTION: Serotonin syndrome is a potentially life-threatening condition characterized by the triad of mental status changes, autonomic instability, and neuromuscular changes. We report a case of serotonin syndrome masquerading as disease flare in a lupus nephritis patient with end-stage renal disease receiving linezolid for the treatment of infected pseudoaneurysm. CASE REPORT: A 36-year-old female lupus nephritis patient on maintenance hemodialysis for end-stage renal disease had been on multiple antibiotics, including anti-tuberculosis medications, over the past month for infected pseudoaneurysm complicating her arteriovenous fistula. Due to minimal response, she underwent pseudoaneurysmal ligation and given linezolid. Two days later, she developed chest pain, tachycardia, hypertension, tremors, later accompanied by high-grade fever, diarrhea, insomnia, and body weakness. Although fully awake and oriented, she was markedly agitated, mildly icteric, had hyperreflexia and asthenia with proximal muscle strength graded 3/5 in all extremities. Blood counts revealed anemia and thrombocytopenia; ancillary tests showed aspartate aminotransferase markedly higher than alanine aminotransferase, elevated serum lactate dehydrogenase and creatine kinase, and low C3 levels. Intravenous hydrocortisone was started for a suspected lupus flare. On the background of linezolid, isoniazid, and tramadol administration, serotonin syndrome with rhabdomyolysis was strongly considered. Offending drugs were discontinued, resulting in the dramatic improvement of symptoms and improved strength and well-being. The steroid was successfully tapered to 5 mg/day and a week later, she remained afebrile without recurrence of symptoms. CONCLUSION: Serotonin syndrome should be considered in patients on multiple serotonergic agents on the background of end-stage renal disease. Prompt recognition and distinction from lupus activity can significantly impact management decisions.

7.
Arthritis Care Res (Hoboken) ; 71(12): 1647-1652, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29693320

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. METHODS: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. RESULTS: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. CONCLUSION: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner.

8.
Int J Rheum Dis ; 22(3): 425-433, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30398013

RESUMO

AIM: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. METHOD: The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. RESULTS: The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. CONCLUSION: The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.


Assuntos
Lúpus Eritematoso Sistêmico , Adolescente , Adulto , Idoso , Ásia/epidemiologia , Austrália/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Cooperação Internacional , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
9.
Arthritis Rheumatol ; 71(1): 91-98, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30035365

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with nonspecific signs and symptoms that are also found in other conditions. This study aimed to evaluate manifestations at disease onset and to compare early SLE manifestations to those of diseases mimicking SLE. METHODS: Academic lupus centers in Asia, Europe, North America, and South America collected baseline data on patients who were referred to them during the previous 3 years for possible SLE and who had a symptom duration of <1 year. Clinical and serologic manifestations were compared between patients diagnosed as having SLE and those diagnosed as having SLE-mimicking conditions. Diagnostic performance of the 1997 American College of Rheumatology (ACR) SLE classification criteria and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria was tested. RESULTS: Data were collected on 389 patients with early SLE and 227 patients with SLE-mimicking conditions. Unexplained fever was more common in early SLE than in SLE-mimicking conditions (34.5% versus 13.7%, respectively; P < 0.001). Features less common in early SLE included Raynaud's phenomenon (22.1% versus 48.5%; P < 0.001), sicca symptoms (4.4% versus 34.4%; P < 0.001), dysphagia (0.3% versus 6.2%; P < 0.001), and fatigue (28.3% versus 37.0%; P = 0.024). Anti-double-stranded DNA, anti-ß2 -glycoprotein I antibodies, positive Coombs' test results, autoimmune hemolytic anemia, hypocomplementemia, and leukopenia were more common in early SLE than in SLE-mimicking conditions. Symptoms detailed in the ACR and SLICC classification criteria were significantly more frequent among those with early SLE. Fewer patients with early SLE were not identified as having early SLE with use of the SLICC criteria compared to the ACR criteria (16.5% versus 33.9%), but the ACR criteria demonstrated higher specificity than the SLICC criteria (91.6% versus 82.4%). CONCLUSION: In this multicenter cohort, clinical manifestations that could help to distinguish early SLE from SLE-mimicking conditions were identified. These findings may aid in earlier SLE diagnosis and provide information for ongoing initiatives to revise SLE classification criteria.


Assuntos
Doenças Autoimunes/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Sjogren/diagnóstico , Adulto , Anemia Hemolítica Autoimune/etiologia , Anticorpos Antinucleares , Síndrome Antifosfolipídica/diagnóstico , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/imunologia , Teste de Coombs , DNA/imunologia , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Feminino , Febre de Causa Desconhecida/etiologia , Hepatite Autoimune/diagnóstico , Humanos , Leucopenia/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Síndrome de Sjogren/etiologia , Tireoidite Autoimune/diagnóstico , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico , Adulto Jovem , beta 2-Glicoproteína I/imunologia
10.
Clin Pharmacol Ther ; 106(2): 374-382, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30079582

RESUMO

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).

11.
Kidney Int ; 95(1): 219-231, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420324

RESUMO

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Adulto , Inibidores de Calcineurina/efeitos adversos , Ciclosporina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Indução de Remissão/métodos , Resultado do Tratamento , Adulto Jovem
12.
Ann Rheum Dis ; 77(6): 890-897, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29550766

RESUMO

OBJECTIVES: To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). METHODS: Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. RESULTS: Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. CONCLUSION: S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. TRIAL REGISTRATION NUMBER: NCT02404350; Results.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/imunologia , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Radiografia , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Clin Pharmacol Ther ; 103(6): 1074-1082, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28925027

RESUMO

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI <80% or MMAS-8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).

14.
Lupus Sci Med ; 4(1): e000214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214036

RESUMO

Objectives: Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Methods: Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping. Autoantibodies were detected by a bead-based multiplex assay. Results were analysed by Fisher's exact test, Student's t-test, χ2 test and one-way analysis of variance, as appropriate for the question. Results: Filipino patients with SLE had increased seroprevalence and elevated antibody concentrations against EBV viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of EBV reactivation, was dramatically increased in patients with SLE compared with unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA seropositivity correlated with lupus-associated autoantibodies (p<0.001), most notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A (p<0.01). Patient and unrelated control sera reacted to the highly repetitive glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was identified in sera of patients with SLE and showed limited binding by FDR and control sera. Conclusions: Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens, along with altered anti-EBNA-1 specificities. EBV reactivation is more common among Filipino patients with SLE compared with healthy Filipinos and may contribute to SLE pathogenesis in this population.

15.
Arthritis Res Ther ; 19(1): 62, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28320433

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE. METHODS: HR-QoL was measured using the Medical Outcomes Study 36-item short form health survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS. RESULTS: Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p < 0.001), a higher level of education (p < 0.001), younger age (p < 0.001) and shorter disease duration (p < 0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p < 0.001) was negatively associated with PCS, and cutaneous activity (p = 0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p < 0.001) and MCS (p < 0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p < 0.001), but not MCS scores. CONCLUSIONS: Ethnicity, education, disease damage and specific organ involvement impacts HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.


Assuntos
Nível de Saúde , Lúpus Eritematoso Sistêmico/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Modelos Lineares , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Análise Multivariada , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
Semin Arthritis Rheum ; 46(6): 798-803, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28216192

RESUMO

OBJECTIVE: To evaluate the construct validity of the Lupus Low Disease Activity State (LLDAS), a treatment target in systemic lupus erythematosus (SLE). METHODS: Fifty SLE case summaries based on real patients were prepared and assessed independently for meeting the operational definition of LLDAS. Fifty international rheumatologists with expertise in SLE, but with no prior involvement in the LLDAS project, responded to a survey in which they were asked to categorize the disease activity state of each case as remission, low, moderate, or high. Agreement between expert opinion and LLDAS was assessed using Cohen's kappa. RESULTS: Overall agreement between expert opinion and the operational definition of LLDAS was 77.96% (95% CI: 76.34-79.58%), with a Cohen's kappa of 0.57 (95% CI: 0.55-0.61). Of the cases (22 of 50) that fulfilled the operational definition of LLDAS, only 5.34% (59 of 22 × 50) of responses classified the cases as moderate/high activity. Of the cases that did not fulfill the operational definition of LLDAS (28 of 50), 35.14% (492 of 28 × 50) of responses classified the cases as remission/low activity. Common reasons for discordance were assignment to remission/low activity of cases with higher corticosteroid doses than defined in LLDAS (prednisolone ≤ 7.5mg) or with SLEDAI-2K >4 due to serological activity (high anti-dsDNA antibody and/or low complement). CONCLUSIONS: LLDAS has good construct validity with high overall agreement between the operational definition of LLDAS and expert opinion. Discordance of results suggests that the operational definition of LLDAS is more stringent than expert opinion at defining a low disease activity state.


Assuntos
Prova Pericial , Lúpus Eritematoso Sistêmico/diagnóstico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
17.
Ann Rheum Dis ; 76(3): 554-561, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27884822

RESUMO

OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. METHODS: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. RESULTS: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. CONCLUSIONS: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/uso terapêutico , Anticorpos Antinucleares/sangue , Antimaláricos/uso terapêutico , Proteínas do Sistema Complemento/metabolismo , Consenso , DNA/imunologia , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Quimioterapia de Manutenção , Indução de Remissão , Índice de Gravidade de Doença , Exacerbação dos Sintomas
18.
Best Pract Res Clin Rheumatol ; 30(3): 398-419, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27886939

RESUMO

This chapter discusses the challenges faced in the development and implementation of musculoskeletal (MSK) Models of Care (MoCs) in middle-income and low-income countries in Asia and outlines the components of an effective MoC for MSK conditions. Case studies of four such countries (The Philippines, Malaysia, Bangladesh and Myanmar) are presented, and their unique implementation issues are discussed. The success experienced in one high-income country (Singapore) is also described as a comparison. The Community Oriented Program for Control of Rheumatic Diseases (COPCORD) project and the role of Asia Pacific League of Associations for Rheumatology (APLAR), a professional body supporting MoC initiatives in this region, are also discussed. The experience and lessons learned from these case studies can provide useful information to guide the implementation of future MSK MoC initiatives in other middle-income and low-income countries.


Assuntos
Assistência à Saúde/métodos , Doenças Musculoesqueléticas/terapia , Ásia , Países em Desenvolvimento , Humanos , Malásia
19.
Arthritis Res Ther ; 18(1): 260, 2016 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-27829463

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE. METHODS: Data were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS. RESULTS: Of the 1846 patients assessed, criteria for LLDAS were met by 44 %. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95 % CI 0.19-0.49, p < 0.001). Likewise, patients with a history of discoid rash (OR 0.66, 95 % CI 0.49-0.89, p = 0.006), renal disease (OR 0.60, 95 % CI 0.48-0.75, p < 0.001), elevated double stranded DNA (OR 0.65, 95 % CI 0.53-0.81, p < 0.001) or hypocomplementaemia (OR 0.52, 95 % CI 0.40-0.67, p < 0.001) were less likely to be in LLDAS. When countries were compared, higher national social wealth (OR 1.57, 95 % CI 1.25-1.98, p < 0.001) as measured by the gross domestic product per capita was positively associated with LLDAS, but ethnicity was not. CONCLUSION: The lupus low disease activity state is observed in less than half of patients with SLE at a single point in time. Disease duration and phenotype, and national social wealth, are predictive of LLDAS.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino
20.
Arthritis Res Ther ; 18: 82, 2016 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-27038608

RESUMO

BACKGROUND: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA). METHODS: In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed. RESULTS: Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP. CONCLUSIONS: CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01217086 . Registered 4 Oct 2010.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Infliximab/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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