Alícia Dorneles Dornelles

Quality of Life of Brazilian Patients with Gaucher Disease and Fabry Disease

OBJECTIVE To evaluate QoL in a sample of Brazilian patients with Gaucher (GD) and Fabry (FD) disease using the SF-36 survey. METHOD Observational cross-sectional study. The SF-36 survey was administered to cognitively able patients 12 years or older, who were seen in the Medical Genetics Service of Hospital de Clínicas de Porto Alegre, Brazil. RESULTS Thirty-five patients were included in the study (GD = 21, FD = 14), mean age was 29.8 ± 14.2 years and 29 (82.9%) were receiving ERT. Patients with GD receiving ERT had better scores in the general health (p = 0.046) domain of the SF-36 than patients with FD receiving ERT. Comparison of patients with GD naive to ERT and those receiving ERT revealed differences only in the bodily pain domain (p = 0.036). The Zimran score showed a moderate negative correlation with the following domains of the SF-36: physical functioning (p = 0.035), role-physical (p = 0.036), general health (p = 0.023) and role emotional (p = 0.021). DISCUSSION AND CONCLUSION Although limited because of the small number of patients included, findings suggest that patients with GD receiving ERT have a better QoL than patients with FD or with GD not receiving ERT. Imiglucerase has a beneficial effect against pain for patients with GD. Further studies should be conducted to confirm our findings.

Efficacy and safety of intravenous laronidase for mucopolysaccharidosis type I: A systematic review and meta-analysis

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease caused by deficient activity of alpha-L-iduronidase. Intravenous (IV) enzyme replacement therapy (ERT) with laronidase is currently used for treating patients with MPS I. Objective To evaluate the efficacy and safety of IV laronidase for MPS I. Methods A systematic literature review was performed by searching the ClinicalTrials.gov, MEDLINE/PubMed, EMBASE, LILACS, and Cochrane Library databases, limited to clinical trials published until December 31, 2016. The first inclusion criterion was being a randomized controlled trial (RCT). If < five RCTs were identified, open-label and nonrandomized trials, controlled or uncontrolled (quasi-experimental), including ≥ five patients, and evaluating relevant outcomes defined a priori, would also be included. For meta-analysis, primary inferences were based on random-effects models. Assessment of article quality was performed in accordance with the GRADE criteria. The Cochrane Risk of Bias tool was used to examine the risk of bias for RCTs. Results The selection phase retrieved 632 articles. During the first phase of selection, 158 had the abstract or full text read for assessment of eligibility, of which nine (two RCTs) were included for qualitative synthesis. Four papers were included in the meta-analysis, which was performed for the following outcomes: occurrence of treatment-emergent or infusion-related adverse events (65%; 95%CI 53, 76), mild in most cases; development of IgG antibodies to laronidase (88%; 95%CI 67, 100); apnea-hypopnea index (not significant—NS), urinary glycosaminoglycans (GAGs) [mean change -65.5 μg/mg creatinine (95%CI -68.8, -62.3)], liver size [mean change -31.03% (95%CI -36.1, -25.9)], left ventricular mass index (LVMI) [mean change -1.8 (95%CI -2.32, -0.25)], and distance covered in the 6-minute walk test (NS). Among the outcomes not included in meta-analysis, we found evidence for benefit of laronidase only on shoulder flexion. Conclusions Our findings suggest that IV laronidase effectively reduces urinary GAGs excretion, hepatomegaly and LVMI, and can improve shoulder flexion in MPS I patients. Laronidase appears to be safe in the studied population.

Efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II with and without comparison to placebo: systematic review and meta-analysis

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.A mucopolissacaridose tipo II (MPS II) e uma doenca genetica de amplo espectro clinico, caracterizada por deficiencia da enzima iduronato-2sulfatase. Revisao sistematica avaliou a eficacia e seguranca da terapia de reposicao enzimatica (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados ate 30 de novembro de 2012. Apenas cinco estudos preencheram os criterios de inclusao (ensaios clinicos randomizados - ECRs, ECRs abertos ou series de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanalise foi realizada para capacidade vital forcada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudancas significativas em ambas as variaveis; tambem foi encontrado risco aumentado de reacoes leves relacionadas a infusao e de desenvolvimento de anticorpos IgG a IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS e segura e tem beneficio potencial em MPS II, mas estudos adicionais sao necessarios.

PP044 Adherence To Enzyme Replacement Therapy In Gaucher Disease

No publications reporting on flare/pseudoseptic reactions with Synolis V-A were found. There are limited case series of patients treated with Synolis V-A, with most evidence coming from a prospective post-marketing surveillance case series, which showed reduced pain and functional impairment at 6 months. Adverse reactions were rare. CGH’s own small trial of Synolis V-A did not show any flare reactions.

Eficácia e segurança da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem comparação com placebo: revisão sistemática e metanálise

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.A mucopolissacaridose tipo II (MPS II) e uma doenca genetica de amplo espectro clinico, caracterizada por deficiencia da enzima iduronato-2sulfatase. Revisao sistematica avaliou a eficacia e seguranca da terapia de reposicao enzimatica (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados ate 30 de novembro de 2012. Apenas cinco estudos preencheram os criterios de inclusao (ensaios clinicos randomizados - ECRs, ECRs abertos ou series de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanalise foi realizada para capacidade vital forcada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudancas significativas em ambas as variaveis; tambem foi encontrado risco aumentado de reacoes leves relacionadas a infusao e de desenvolvimento de anticorpos IgG a IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS e segura e tem beneficio potencial em MPS II, mas estudos adicionais sao necessarios.

Eficacia y seguridad del tratamiento con idursulfasa en pacientes con mucopolisacaridosis tipo II con y sin comparación con el placebo: revisión sistemática y metaanálisis

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.A mucopolissacaridose tipo II (MPS II) e uma doenca genetica de amplo espectro clinico, caracterizada por deficiencia da enzima iduronato-2sulfatase. Revisao sistematica avaliou a eficacia e seguranca da terapia de reposicao enzimatica (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados ate 30 de novembro de 2012. Apenas cinco estudos preencheram os criterios de inclusao (ensaios clinicos randomizados - ECRs, ECRs abertos ou series de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanalise foi realizada para capacidade vital forcada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudancas significativas em ambas as variaveis; tambem foi encontrado risco aumentado de reacoes leves relacionadas a infusao e de desenvolvimento de anticorpos IgG a IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS e segura e tem beneficio potencial em MPS II, mas estudos adicionais sao necessarios.

Hyperimmunoglobulinemia in pediatric Gaucher patients in Southern Brazil

To the Editor: We read with great interest the brief report published by Arıkan-Ayyıldız et al. [1] about immunoglobulin abnormalities and enzyme replacement therapy (ERT) in children with Gaucher disease (GD). We would like to point out some issues based on the findings of the cohort of Gaucher patients followed in our clinics. Since 2003, all patients (30 GD type I and 3 GD type III) are followed with clinical assessment and complementary exams every 3 months and after achievement of main goals, laboratory exams, including immunological profile (IgG, IgM, IgA, and IgE, as well as electrophoresis of proteins) are done on a yearly basis [2,3]. Evaluation of immunological data at the diagnosis was performed for 11 patients (9 GD type I and 2 GD type III) who were under the age of 18 years at the diagnosis. All but one pediatric patient (GD type III patient due to allergic reaction) have been receiving ERT with imiglucerase (30 U/kg/inf for GD type I and 60 U/kg/inf for GD type III) every 2 weeks. The mean age at diagnosis was 6.4 years (range: 2–16 years) and the mean age at the start of treatment was 7 years (range: 2–17 years). The mean time of ERT was 12.7 years (range: 8–16 years). We had access to immunological profiles of eight pediatric patients since 2007 (7 GD type I patients and 1 GD type III patient) and four patients since 2008 (3 GD type I patients and 1 GD type III patient). Hyperimmunoglobulinemia was present in 10 (90.9%) pediatric patients at the first evaluation (IgA: 1/10 patients, IgE: 8/10 patients, IgM: 2/10 patients, IgG: 4/10 patients). The only GD type III patient, who was without ERT, presented IgG monoclonal gammopathy, but after a few months, even without treatment, the monoclonal pike disappeared. Four patients (36.4%) presented polyclonal gammopathy at the first evaluation. One GD type I patient (after 19 months of ERT) and one GD type III patient (after 15 months of ERT) resolved their gammopathy. Even in regular therapy with imiglucerase, nine (90%) patients still present with hyperimmunoglobulinemia (IgE: 6/9 patients, IgM: 2/9 patients, IgG: 6/9 patients). Our data differs from previous studies, including the Brief Report by Ayyıldız et al. [4] that reported a frequency of hyperimmunoglobulinemia in pediatric GD patients ranging from 71% to 77% at diagnosis. Ninety percent of our patients presented hyperimmunoglobulinemia at the first evaluation (23–29% of difference from other studies) and 40% of the patients showed increased levels of IgG, similar to what has been reported [4]. After ERT, the number of patients with hyper IgE decreased 14%, hyper IgM increased 2% and hyper IgG increased 26%. None of our patients resolved their gammopathy. Our data suggest that the cohort of patients in Southern Brazil presents more hyperimmunoglobulinemia than the previous reports and ERT was less effective in normalize immunoglobulin levels. We agreed that the initiation of early ERT might help to decrease the risk of malignancies, but other studies are needed.