Real-world effectiveness and safety of multiple myeloma treatments based on thalidomide and bortezomib: A retrospective cohort study from 2009 to 2020 in a Brazilian metropolis.

BACKGROUND: Multiple myeloma (MM) is an incurable cancer of plasma cells; the survival of which has improved over the years with the emergence of new treatments. In Brazil, the availability of treatment-regimens is different from developed countries. Real-world evidence with Brazilian patients is lacking. OBJECTIVES: Our aim was to evaluate the effectiveness and the safety of MM treatments in a Brazilian metropolis. METHODS: This was a retrospective cohort study with MM patients, beginning MM treatment from 2009 to 2020 (i.e., before bortezomib became available in public health services). Patients' medical records were revised to obtain clinical variables. The primary outcomes were Overall Survival (OS) and Progression Free Survival (PFS, measured as time to next treatment), and the secondary outcomes were Adverse Events (AE). Kaplan-Meier curves were obtained and the Cox proportional hazards model was performed for univariate and multivariate analyses. The incidence of AE was estimated and the chi-squared test was performed to evaluate the association between AE and MM regimens. RESULTS: In total, 278 patients participated in the study with median age of 64 years; 50.4 % were females, 55.8 % attended a private clinic, 34.9 % received autologous stem cell transplantation (ASCT) and 32.4 % were on polypharmacy. Most patients from public services used thalidomide-based regimens (40.3 %) and at private clinics used bortezomib-based regimens (38.1 %) as first-line treatment. Patients had a median OS of 99 months. Patients had median PFS of 28 months in first-line treatment, which was significantly different for age (p = 0.0055), polypharmacy (p = 0.0094) and ASCT (p < 0.0001). PFS was independently associated to polypharmacy and ASCT. The incidence of peripheral neuropathy (39.6 %) was high. In contrast, the incidence of severe AE was low. We found significant difference between first-line T + B-based regimens and leukopenia (p = 0.012). CONCLUSION: Our study showed that patients on polypharmacy and who did not receive ASCT had worse PFS. Similar to other Latin countries, most patients used thalidomide- and bortezomib-based regimens as first-line treatments having similar OS and PFS. Treatments were considered relatively safe, especially regarding serious AE.

Use of fall risk-increasing drugs in older adults with multiple myeloma: A cross-sectional study.

OBJECTIVE: To investigate the use of fall risk-increasing drugs (FRIDs) and associated factors and to assess the use of medicines that induce neuropathy in older adults with multiple myeloma (MM). METHODS: Cross-sectional study with older adults with MM treated at the outpatient oncology and hematology services in a southeastern Brazilian capital. FRIDs were classified according to the Screening Tool of Older Persons Prescription in older adults with high fall risk (STOPPFall). The high risk of falling was defined using the Medication Fall Risk Score scale, and the medicines that induce neuropathy were identified according to Vilholm et al. (2014) and Jones et al. (2019). Univariate and multivariate analyses were performed to verify the association between variables. RESULTS: Approximately 54.2% of the 153 older adults included in the study were female, and the median age was 70.9 years (IQR = 13; min = 60 and max:92). Around 71.3% used FRIDs, and diuretics (25.6%), antidepressants (20.5%), and opioids (19.9%) were the most used. A total of 32.7% had a high risk of falling. Polypharmacy was associated with a higher risk of using FRIDs. Statins used concomitantly with immunomodulators or bortezomib were the most used neuropathyinducing drugs, increasing fourfold the likelihood of reporting peripheral neuropathy. CONCLUSION: The frequency of use of FRIDs is high in older adults with MM and is positively associated with polypharmacy.

Effect of therapeutic regimens and polypharmacy on health-related quality of life of people with multiple myeloma: a cross-sectional study in Belo Horizonte, Brazil.

OBJECTIVE: Multiple myeloma (MM) is an incurable hematological cancer and its treatment is geared to promote better Health-Related Quality of Life (HRQoL). We aimed to assess HRQoL and compare scores between variables on therapeutic regimens and polypharmacy in MM patients. METHODS: This cross-sectional study was performed from April/2019 to February/2020 in Belo Horizonte, Brazil. HRQoL scores were obtained by the QLQ-C30 and QLQ-MY20 instruments. Data were retrieved from interviews and medical records. Therapeutic regimens were grouped into thalidomide-containing regimens; bortezomib-containing regimens; bortezomib and thalidomide-containing regimens; other therapeutic regimens, and remission group. We performed univariate analyses by the Mann-Whitney method and adopted the Kruskal-Wallis test for multiple comparisons. Robust multiple linear regression was used to determine the association between independent variables and the HRQoL scores. RESULTS: The sample included 225 participants and most patients (65.3%) were on active treatment and had worse scores concerning future perspective. Polypharmacy was associated with worse scores on all scales in the univariate analyses. We observed a difference in the global health and body image (p < .05) scales in the multiple comparisons with therapeutic regimens. The global health scale difference was found between groups with other regimens and the remission group (p < .05). The difference between the bortezomib and thalidomide-containing regimens and remission group was not statistically significant (p = .077) in the body image scale. The multiple linear regression maintained the association of polypharmacy with worse HRQoL scores. CONCLUSION: We identified an independent association between HRQoL and polypharmacy in MM patients. However, there was no difference between the evaluated regimens, suggesting they are equivalent in Brazil about HRQoL.

A phase IV, prospective, observational study of the clinical safety of snake antivenoms.

Snake envenoming is a neglected tropical disease that affects more than 2.7 million people worldwide. The treatment is based on the administration of antivenom composed of heterologous immunoglobulins, species-specific therapy involving the possibility of adverse reactions due to activation of the immune system. Considering the scarcity of prospective studies evaluating the safety of snake antivenoms, this study aimed to describe and characterize adverse events after antivenom infusion in an observational, prospective, single-centre investigation conducted in a referral centre in Brazil. A total of 47 victims of snake envenoming were included in the study, who were mostly men (75%), with ages ranging from 2 to 83 years. Twenty-two participants (47%) presented manifestations compatible with infusion-related reactions (IRRs) during or up to two hours after F(ab')2 heterologous immunoglobulin infusion. The most common clinical manifestation related to the infusion was a diffuse cutaneous rash (82%), followed by respiratory manifestations (46%) and facial swelling (23%). In four cases (9%), IRR were considered serious adverse events (SAE), characterized by haemodynamic instability, airway obstruction or hypoxia. Only one patient developed symptoms compatible with serum sickness. Although almost half of the patients treated with antivenom sera experienced IRRs, the SAE rate was 9%; in all cases, the adverse reaction was reversible by using supportive treatment, and there were no deaths. The results have shown that there is much to improve in the antivenom production process to obtain a more purified and specific product. Even so, a timely antivenom serum administration managed by well-trained health teams is safe and prevents complications after snake-related accidents.

Thalidomide control and use: are these appropriate to extend the use and mitigate the risk of teratogenicity in Brazil? / Controle e utilização da talidomida: adequados à ampliação do uso e mitigação do risco de teratogenicidade no Brasil?

Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.

Estudo de utilização de medicamento que descreve o controle da talidomida no Brasil e sua utilização em Minas Gerais. Questionário online foi enviado às unidades federativas do Brasil para coleta de dados de distribuição, dispensação, cadastro de usuários e eventos adversos da talidomida. Dados de distribuição (2011-2018) e dispensação (2015-2018) de Minas Gerais foram obtidos pelo sistema de gerenciamento da assistência farmacêutica. Análise de variância e teste de Tukey foram empregados para comparações dos dados. Das 16 unidades federativas participantes, 100% e 50% utilizavam sistema eletrônico para distribuição e dispensação, respectivamente, e cerca de 43% cadastravam usuários. Sistemas de notificação de eventos adversos eram escassos. Houve redução de 44% na distribuição em Minas Gerais no período. A dispensação manteve-se constante (média 0,0004 DDD/1000 hab./dia) e ocorreu principalmente para eritema nodoso hansênico e mieloma múltiplo. O uso off-label (2,2%) foi crescente. A maioria dos usuários era do sexo masculino (idade média 56 anos). Das mulheres, 30% estavam em idade fértil. A vigilância da talidomida é um desafio em saúde pública. Apesar da ampliação do uso e obrigatoriedade de controle, não há padronização em nível nacional e a notificação de eventos adversos é incipiente.

Controle e utilização da talidomida: adequados à ampliação do uso e mitigação do risco de teratogenicidade no Brasil? / Thalidomide control and use: are these appropriate to extend the use and mitigate the risk of teratogenicity in Brazil?

Resumo Estudo de utilização de medicamento que descreve o controle da talidomida no Brasil e sua utilização em Minas Gerais. Questionário online foi enviado às unidades federativas do Brasil para coleta de dados de distribuição, dispensação, cadastro de usuários e eventos adversos da talidomida. Dados de distribuição (2011-2018) e dispensação (2015-2018) de Minas Gerais foram obtidos pelo sistema de gerenciamento da assistência farmacêutica. Análise de variância e teste de Tukey foram empregados para comparações dos dados. Das 16 unidades federativas participantes, 100% e 50% utilizavam sistema eletrônico para distribuição e dispensação, respectivamente, e cerca de 43% cadastravam usuários. Sistemas de notificação de eventos adversos eram escassos. Houve redução de 44% na distribuição em Minas Gerais no período. A dispensação manteve-se constante (média 0,0004 DDD/1000 hab./dia) e ocorreu principalmente para eritema nodoso hansênico e mieloma múltiplo. O uso off-label (2,2%) foi crescente. A maioria dos usuários era do sexo masculino (idade média 56 anos). Das mulheres, 30% estavam em idade fértil. A vigilância da talidomida é um desafio em saúde pública. Apesar da ampliação do uso e obrigatoriedade de controle, não há padronização em nível nacional e a notificação de eventos adversos é incipiente.

Abstract Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.

Adverse events in patients with leprosy on treatment with thalidomide.

INTRODUCTION: Thalidomide, used to treat erythema nodosum leprosum (ENL), is associated with severe adverse events (AEs) and is highly teratogenic. METHODS: A cross-sectional study was conducted on thalidomide-treated patients with ENL. AEs and selected variables were investigated through interviews and assessment of medical records. Odds ratios with 95% confidence intervals were estimated via logistic regression. RESULTS: Peripheral neuropathy symptoms and deep vein thrombosis (DVT) were the most common AEs reported. Although women of reproductive age used contraceptives, <50% of patients reported using condoms. Polypharmacy was associated with all endpoints, except DVT. CONCLUSIONS: Pharmacovigilance is crucial to prevent harmful thalidomide-associated AEs.

Adverse events in patients with leprosy on treatment with thalidomide

Abstract INTRODUCTION: Thalidomide, used to treat erythema nodosum leprosum (ENL), is associated with severe adverse events (AEs) and is highly teratogenic. METHODS: A cross-sectional study was conducted on thalidomide-treated patients with ENL. AEs and selected variables were investigated through interviews and assessment of medical records. Odds ratios with 95% confidence intervals were estimated via logistic regression. RESULTS: Peripheral neuropathy symptoms and deep vein thrombosis (DVT) were the most common AEs reported. Although women of reproductive age used contraceptives, <50% of patients reported using condoms. Polypharmacy was associated with all endpoints, except DVT. CONCLUSIONS: Pharmacovigilance is crucial to prevent harmful thalidomide-associated AEs.

Identification of continuous interaction sites in PLA(2)-based protein complexes by peptide arrays.

Crotoxin (CA.CB) is a beta-neurotoxin from Crotalus durissus terrificus snake venom that is responsible for main envenomation effects upon biting by this snake. It is a heterodimer of an acidic protein (CA) devoid of any biological activity per se and a basic, enzymatically active, PLA(2) counterpart (CB). Both lethal and enzymatic activities of crotoxin have been shown to be inhibited by CNF, a protein from the blood of C. d. terrificus snakes. CNF replaces CA in the CA.CB complex, forming a stable, non-toxic complex CNF.CB. The molecular sites involved in the tight interfacial protein-protein interactions in these PLA(2)-based complexes have not been clearly determined. To help address this question, we used the peptide arrays approach to map possible interfacial interaction sites in CA.CB and CNF.CB. Amino acid stretches putatively involved in these interactions were firstly identified in the primary structure of CB. Further analysis of the interfacial availability of these stretches in the presumed biologically active structure of CB, suggested two interaction main sites, located at the amino-terminus and beta-wing regions. Peptide segments at the carboxyl-terminus of CB were also suggested to play a secondary role in the binding of both CA and CNF.

Contribuição da FUNED para a produção de soros antivenenos e antitóxicos no Brasil

O artigo apresenta um breve relato da situação dos acidentes por animais

venenosos e produção de antivenenos.Destaca a produção de soros antiofídicos

e antitóxicos da FUNED, que foi iniciada juntamente com a sua fundação.

Enfatiza a relevante contribuição da FUNED para a auto-suficiência de

um produto estratégico e a manutenção de um programa bem sucedido

do Ministério da Saúde, o Programa Nacional de Imunizações, que garante,

gratuitamente, um produto de qualidade a pacientes em todo o território