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1.
Medicine (Baltimore) ; 99(40): e22639, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019487

RESUMO

INTRODUCTION: Tuberculous meningitis (TBM) is the most fatal type of tuberculosis in which corticosteroids are added with antitubercular therapy to prevent permanent brain damage. However, this treatment may produce paradoxical reactions. In such cases, thalidomide use might reduce central nervous system inflammation and improve the outcome. We present the case of a human immunodeficiency virus-negative patient with TBM who developed paradoxical reactions manifesting as multiple intracranial tuberculomas that were resistant to standard care (antitubercular drugs and corticosteroids) but responded well to thalidomide. PATIENT'S MAIN CONCERN AND CLINICAL FINDINGS: The patient was a 40-year-old Chinese female, who was admitted with a 10-day history of headaches, night sweats, and cough. She was healthy before contracting the infection and had no history of contact with tuberculosis patients. DIAGNOSES, INTERVENTION, AND OUTCOME: We diagnosed the patient with TBM complicated by the occurrence of pulmonary tuberculosis. Positive results were obtained from Gram and Ziehl-Neelsen staining of the sputum and acid-fast bacilli sputum culture. Standard treatment was initiated with antitubercular drugs (daily isoniazid, rifampicin, ethionamide, and pyrazinamide) and corticosteroids (dexamethasone). However, 3 months later the magnetic resonance imaging of the head revealed some new tuberculoma lesion. Thus, a specific therapy of antitubercular drugs and thalidomide was introduced. On completion of a 12-month course of antitubercular drugs with 2 months of thalidomide, the patient showed favorable outcomes without neurologic sequelae. Moreover, thalidomide appeared safe and well tolerated in the patient. CONCLUSION: In addition to the specific anti-tubercular and adjuvant corticosteroid therapies for TBM, thalidomide can be used as a "salvage" antitubercular drug in cases that are unresponsive to corticosteroids.


Assuntos
HIV/imunologia , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Pulmonar/complicações , Corticosteroides/uso terapêutico , Adulto , Antituberculosos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Encéfalo/patologia , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Imagem por Ressonância Magnética/métodos , Terapia de Salvação , Resultado do Tratamento , Tuberculoma/diagnóstico por imagem , Tuberculose Meníngea/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
4.
PLoS Negl Trop Dis ; 14(8): e0008329, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760161

RESUMO

The drug thalidomide has resurged in the world market under restrictive conditions for marketing and use. In Brazil, there are still cases of pregnant women using thalidomide even after the implementation of laws that regulate the control of use (Law No. 10.651/2003 and Collegiate Board Resolution No. 11/2011). The objective of this study was to discuss the control of thalidomide use in Brazil, based on a scoping review of the scientific literature, documents, and data from the Ministry of Health. A total of 51 studies and documents related to the following subthemes were selected: (1) organization of access and use of thalidomide in the health system; (2) epidemiological and population characteristics of people affected by leprosy; and (3) occurrence of pregnancy and cases of embryopathy with the use of thalidomide. The results showed that Brazil has no unified information database about thalidomide patients. Furthermore, there is inconsistency in the accreditation of public health centers that dispense this medicine, in a country that has a high consumption of thalidomide in the Unified Health System. A large part of this amount of dispensed medicine is intended for the treatment of erythema nodosum leprosum, mainly in the North, Northeast, and Central-West regions of the country, which are endemic for leprosy. This disease is the only one among the clinical indications of the medicine approved in Brazil that does not have a Clinical Protocol and Therapeutic Guidelines. The control of thalidomide use in Brazil presents historical regulatory failures. These are currently linked to the organization and structure of primary healthcare in the country, as well as to the lack of leadership of the Ministry of Health and National Health Surveillance Agency when it comes to managing the process of control of this use.


Assuntos
Hanseníase/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Anormalidades Induzidas por Medicamentos/epidemiologia , Brasil/epidemiologia , Eritema Nodoso/tratamento farmacológico , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase/epidemiologia , Hanseníase Virchowiana/tratamento farmacológico , Masculino , Gravidez
5.
Drugs Aging ; 37(9): 657-663, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32696432

RESUMO

INTRODUCTION: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. METHODS: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. RESULTS: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65-74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65-74 and 75-84 years subgroups than in the > 85 years subgroup (p = 0.01). CONCLUSION: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Administração Oral , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Feminino , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 4/administração & dosagem , Inibidores da Fosfodiesterase 4/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do Tratamento
6.
Zhonghua Er Ke Za Zhi ; 58(7): 570-575, 2020 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-32605341

RESUMO

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P<0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P<0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P=0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P<0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Criança , Pré-Escolar , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Nutrição Enteral , Fármacos Gastrointestinais/uso terapêutico , Humanos , Lactente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Infliximab/uso terapêutico , Talidomida/uso terapêutico
7.
Scott Med J ; 65(3): 72-75, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32638647

RESUMO

Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Rituximab/uso terapêutico , Talidomida/uso terapêutico , Administração Intravenosa , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada/métodos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Rituximab/administração & dosagem , Talidomida/administração & dosagem
8.
Brasília; s.n; 5 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100288

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 7 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ácido Ascórbico/uso terapêutico , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Talidomida/uso terapêutico , Ceftriaxona/uso terapêutico , Metilprednisolona/uso terapêutico , Cloroquina/uso terapêutico , Interferons/uso terapêutico , Enoxaparina/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Lopinavir/uso terapêutico , Inibidores de Vasopeptidases/uso terapêutico , Hidroxicloroquina/uso terapêutico
9.
Dermatol Ther ; 33(4): e13722, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32475036

RESUMO

Time to improvement is a crucial characteristic for effective treatments of chronic inflammatory conditions, such as psoriasis. Apremilast is a recently approved drug, belonging to the small molecule phosphodiesterase 4 inhibitors, whose optimal safety and efficacy profile is somewhat affected by slow activity rate in clinical trials. Real world case series are suggesting a more consistent improvement, and with this additional personal investigation on 48 patients, we signal that 58% of patients achieved Psoriasis Area and Severity Index (PASI) 50, and 19% PASI 75 improvement in the first 8 weeks of treatment. Results at 16-week are remarkable, with overall 55% of patients achieving PASI 75, 21% PASI 90 and 14% PASI 100. Only 8 patients (18, 6%) had slightly improved, although satisfied with the regimen, and determined to continue. Noteworthy, our population was rather problematic in terms of comorbidities (86%), and resistance to other treatments, with only 28% naïve to systemics, including biologics. Moreover, the observation period includes the Italian outbreak of COVID-19 epidemic, and further information on apremilast safety are provided, no one of the patients having stopped treatment. In such a critical period, the apremilast satisfactory speed of therapeutic response in a real-world setting has further strengthens patient's compliance to remain safely at home, which is the best strategy to limit contagion.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Psoríase/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Talidomida/uso terapêutico
10.
Front Immunol ; 11: 1248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574274

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threatening health issue. The progression of this viral infection occurs in the airways of the lungs with an exaggerated inflammatory response referred to as the "cytokine storm" that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications of COVID-19 and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs is Thalidomide; a historically emblematic controversial molecule that harbors an FDA approval for treating erythema nodosum leprosum (ENL) and multiple myeloma (MM). Based on just one-case report that presented positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Yet, the absence of substantial evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases, might cause a significant obstacle for carrying out further clinical evaluations. Herein, we will discuss the theoretical effectiveness of Thalidomide in attenuating inflammatory complications that are encountered in COVID-19 patients while pinpointing the lack of the needed evidences to move forward with this drug.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Talidomida/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Progressão da Doença , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia
11.
BMC Neurol ; 20(1): 240, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532281

RESUMO

BACKGROUND: The onset of myasthenia (MG) gravis with anti-muscle-specific tyrosine kinase (MuSK) antibodies most commonly peaks in the fourth decade of life, and MG with MuSK antibodies (MuSK-MG) rarely coexists with a malignant tumor. To date, MuSK-MG has not been reported in multiple myeloma (MM). CASE PRESENTATION: A 60-year-old male with MM who was receiving treatment with bortezomib and thalidomide presented diplopia, ptosis, and limb weakness. A diagnosis of MM with Bence-Jones proteinuria was established when he was 56 years old, and he received chemotherapy with four courses of bortezomib and dexamethasone. Although he received thalidomide as maintenance therapy, it was discontinued a year before hospital admission because of sensory neuropathy as a side effect. Six months before hospital admission, he developed mild diplopia. One month before admission, his chemotherapy was interrupted because of viral infection and fatigability. Then he developed neck weakness and bilateral ptosis. A diagnosis of MuSK-MG was made based on neurological and serological examinations. According to the previous relevant literature, this is the first report of MuSK-MG in a patient with MM. CONCLUSIONS: In patients with MM, the possibility of co-existing of autoimmune disease, including MuSK-MG, should be considered. This case emphasizes the need to still consider testing for anti-MuSK antibodies in older MM patients where there is clinical suspicion for possible MG despite negative anti-acetylcholine receptor antibodies and lacking classic MuSK MG phenotype at onset.


Assuntos
Antineoplásicos/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Miastenia Gravis/complicações , Autoanticorpos/imunologia , Bortezomib/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Talidomida/uso terapêutico
12.
PLoS One ; 15(6): e0232068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559187

RESUMO

Cyclin Dependent Kinase 9 (CDK9) associates with Bromodomain and Extra-Terminal Domain (BET) proteins to promote transcriptional elongation by phosphorylation of serine 2 of RNAP II C-terminal domain. We examined the therapeutic potential of selective CDK9 inhibitors (AZD 4573 and MC180295) against human multiple myeloma cells in vitro. Short-hairpin RNA silencing of CDK9 in Multiple Myeloma (MM) cell lines reduced cell viability compared to control cells showing the dependency of MM cells on CDK9. In order to explore synergy with the CDK9 inhibitor, proteolysis targeting chimeric molecule (PROTAC) ARV 825 was added. This latter drug causes ubiquitination of BET proteins resulting in their rapid and efficient degradation. Combination treatment of MM cells with ARV 825 and AZD 4573 markedly reduced their protein expression of BRD 2, BRD 4, MYC and phosphorylated RNA pol II as compared to each single agent alone. Combination treatment synergistically inhibited multiple myeloma cells both in vitro and in vivo with insignificant weight loss. The combination also resulted in marked increase of apoptotic cells at low dose compared to single agent alone. Taken together, our studies show for the first time that the combination of a BET PROTAC (ARV 825) plus AZD 4573 (CDK9 inhibitor) is effective against MM cells.


Assuntos
Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas/metabolismo , Proteólise/efeitos dos fármacos , Animais , Azepinas/farmacologia , Azepinas/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Camundongos , Camundongos SCID , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Polimerase II/metabolismo , RNA Interferente Pequeno/metabolismo , Talidomida/análogos & derivados , Talidomida/farmacologia , Talidomida/uso terapêutico , Transplante Heterólogo
13.
Zhonghua Nei Ke Za Zhi ; 59(6): 445-450, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32486585

RESUMO

Objective: To analyze the long-term efficacy and safety of thalidomide on refractory Crohn's disease (CD). Methods: A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed. Results: In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95%CI 80.6%-96.6%), 80.7% (95%CI 70.3%-91.1%), 53.7% (95%CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio (HR) of 3.559 for Crohn's disease activity index (CDAI) ≥220(95%CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions: This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.


Assuntos
Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Doença de Crohn/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Talidomida/efeitos adversos
14.
Medicine (Baltimore) ; 99(21): e20221, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481292

RESUMO

RATIONALE: Behcets disease (BD) is a type of chronic systemic vasculitis that typically manifests as a mucocutaneous disease with orogenital ulcers, skin damage, and uveitis. The clinical diagnosis is often difficult because of the diversity of organs that may be involved and lack of specific pathological diagnosis. PATIENT CONCERNS: A 26-year-old woman presented as a nearly 2-week history of hoarseness with throat pain. DIAGNOSES: In the present case, Fiber laryngoscopy showed multiple ulcers involving the epiglottic tubercle, bilateral false vocal cord, middle area of the left vocal cord, and full length of the right vocal cord. Multidisciplinary physicians combined the patients clinical manifestations and pathological findings to make the Behcets disease diagnosis. INTERVENTIONS: As the diagnosis confirmed, immediately began appropriate medical therapy (prednisolone at 30 mg once per day and thalidomide at 50 mg once per night in a month). OUTCOMES: The ulcer on the right vocal cord disappeared but left a scar. Therefore, the patient experienced only partial recovery from the hoarseness. LESSONS: Behcets disease can cause damage to multiple organs. Although the combination of vocal cord ulcers and hoarseness is rare in patients with BD and has not been previously reported to date, such patients should be treated with caution in clinical practice.


Assuntos
Síndrome de Behçet/complicações , Rouquidão/etiologia , Faringite/etiologia , Prega Vocal/patologia , Adulto , Síndrome de Behçet/diagnóstico por imagem , Síndrome de Behçet/tratamento farmacológico , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Laringoscopia/métodos , Faringite/diagnóstico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Resultado do Tratamento , Prega Vocal/diagnóstico por imagem
17.
Drugs Today (Barc) ; 56(5): 303-310, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32406877

RESUMO

Apremilast, an oral small molecule, is a phosphodiesterase 4 (PDE-4) blocker. It has been shown to be efficacious in managing psoriasis (PS) and psoriatic arthritis (PSA). In two controlled studies, it was also effective in controlling oral ulcers of Behçet syndrome (Bsy). The main side effects associated with apremilast are diarrhea, nausea and headaches. These are usually transient and apremilast requires almost no laboratory monitoring during its use. An important issue is whether apremilast will also be useful in other debilitating and life-threatening manifestations of Bsy, for which there is yet no negative or positive evidence. The experience with apremilast use in PS/PSA will surely be helpful in foreseeing and managing potential adverse events of apremilast use for any other indication in Bsy. On the other hand, the author does not consider the proposed similarities in disease mechanisms between PS/PSA and Bsy strong enough to guide us as to where and when to use apremilast in Bsy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Talidomida/análogos & derivados , Síndrome de Behçet/complicações , Humanos , Úlceras Orais/etiologia , Talidomida/uso terapêutico
19.
Lancet Haematol ; 7(5): e381-e394, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171061

RESUMO

BACKGROUND: Treatment of multiple myeloma is not curative, but targeting CD38 improves patient survival. To further explore this therapeutic approach, we investigated the safety and activity of MOR202, a novel monoclonal antibody targeting CD38, in patients with multiple myeloma. METHODS: This is a multicentre, open-label, phase 1-2a trial done at ten hospitals in Germany and Austria. Enrolled patients were aged 18 years or older with relapsed or refractory multiple myeloma and Karnofsky performance status of 60% or higher. Patients were assigned to the different treatment regimens with MOR202 ranging between 0·01 mg/kg and 16 mg/kg in a 3 + 3 design. Dose-escalation and expansion was done either with MOR202 intravenous infusions alone (MOR202 q2w [twice a week] and q1w [weekly] groups) or in combination with dexamethasone (MOR202 with dexamethasone group), with dexamethasone plus pomalidomide (MOR202 with dexamethasone plus pomalidomide group) or plus lenalidomide (MOR202 with dexamethasone plus lenalidomide group). Primary endpoints were safety, MOR202 maximum tolerated dose (or recommended dose) and regimen, and immunogenicity. The primary analysis was assessed in the safety population, which included patients who received at least one dose of any study drug. This trial is registered with ClinicalTrials.gov, NCT01421186. FINDINGS: Between Aug 24, 2011, and Aug 1, 2017, 91 patients were treated, 35 with MOR202 monotherapy, and 56 with MOR202 combination regimens (18 in the MOR202 with dexamethasone group, 21 in the MOR202 with dexamethasone plus pomalidomide group, and 17 in the MOR202 with dexamethasone plus lenalidomide group). MOR202 intravenous infusions were safely administered within 30 min. Infusion-related reactions occurred in 14 (40%) of 35 patients receiving MOR202 monotherapy without steroids, and in four (7%) of 56 patients receiving MOR202 combination treatment. MOR202 maximum tolerated dose was not reached and the recommended regimens were MOR202 administered as an intravenous infusion for 30 min at doses up to 16 mg/kg with dexamethasone (40 mg), or in combination with dexamethasone plus lenalidomide (25 mg) or pomalidomide (4 mg). 35 (38%) of 91 patients developed lymphopenia, 30 (33%) developed neutropenia, and 27 (30%) developed leukopenia; these were the most common grade 3 or higher treatment-emergent adverse events. Serious adverse events were reported in 51 (56%) of 91 patients. None of the deaths were associated with MOR202. One pomalidomide-associated death occurred in the MOR202 with dexamethasone plus pomalidomide group. No anti-MOR202 antibodies were detected in patients. INTERPRETATION: MOR202 is safe and its clinical activity in patients with relapsed or refractory multiple myeloma is promising. Further clinical investigations of combinations with an immunomodulatory drug and dexamethasone are recommended. FUNDING: MorphoSys AG.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do Tratamento
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