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1.
Ann Hematol ; 99(1): 121-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31773215

RESUMO

It is uncertain if different immunomodulatory drugs (IMID) pose distinct thrombotic risk in patients with newly diagnosed multiple myeloma (MM). Among 2397 MM patients from the SEER-Medicare database from 2007 to 2013, 78% received lenalidomide, and 22% received thalidomide. After inverse probability weighting to balance confounders, the 12-month incidences of venous thromboembolism (VTE 10%) and arterial thromboembolism (ATE 5%) were similarly high in both groups. Lenalidomide versus thalidomide had a subdistribution hazard ratio of 1.11 (0.59-2.02) for VTE and a subdistribution hazard ratio of 0.96 (0.45-1.98) for ATE. Overall survival was not significantly different with a hazard ratio of 0.88 (0.60-1.18) for lenalidomide versus thalidomide. Concurrent anticoagulant prophylaxis was infrequently prescribed in < 20% of both groups. Our study demonstrates that despite improvement in myeloma-directed therapy and supportive care, thrombosis remains an important consideration for all IMID-treated MM patients. Appropriate risk stratification and vigilant thromboprophylaxis remain essential to prevent this complication.


Assuntos
Lenalidomida , Mieloma Múltiplo , Sistema de Registros , Talidomida , Tromboembolia , Idoso , Feminino , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Estudos Retrospectivos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologia
3.
N Engl J Med ; 381(20): 1918-1928, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722152

RESUMO

BACKGROUND: The small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behçet's syndrome. In a phase 2 trial involving patients with Behçet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behçet's syndrome who had active oral ulcers and had not previously received biologic agents are limited. METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behçet's syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behçet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed. RESULTS: A total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to -54.6; P<0.001). The change from baseline in the Behçet's Disease Quality of Life score was -4.3 points in the apremilast group, as compared with -1.2 points in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 to -1.3). Adverse events with apremilast included diarrhea, nausea, and headache. CONCLUSIONS: In patients with oral ulcers associated with Behçet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.).


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Inibidores da Fosfodiesterase 4/uso terapêutico , Talidomida/análogos & derivados , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Área Sob a Curva , Síndrome de Behçet/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Úlceras Orais/etiologia , Inibidores da Fosfodiesterase 4/efeitos adversos , Qualidade de Vida , Talidomida/efeitos adversos , Talidomida/uso terapêutico
4.
Cien Saude Colet ; 24(10): 3783-3792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577009

RESUMO

In April 2017, the National Sanitary Surveillance Agency (ANVISA-Brazil) approved lenalidomide (LEN) for multiple myeloma (MM) and myelodysplastic syndrome. ANVISA had rejected the first application in 2010, and denied a request for reconsideration in 2012. The reason for rejection was the lack of comparative effectiveness studies proving that LEN was more effective than thalidomide (THAL), a strictly controlled drug regulated by Federal law 10.651/2003 and dispensed to patients (at no costs) through public health system units and hospitals. ANVISA unexplained retreat on the LEN approval for marketing was an unquestionable triumph of the lobbying that ensued the denial, at the forefront of which were politicians, Congress members, patient organizations and medical societies. Two randomized (phase III) trials and three observational (case-control and population-based cohort) compared the effectiveness of THAL- versus LEN-based therapies in MM. Overall, these studies showed no difference in efficacy between LEN- and THAL-based therapies. LEN caused less neuropathy, and more severe hematologic adverse effects. It is much costlier than THAL, and substitution of THAL by LEN shall raise considerably public healthcare costs in Brazil.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Controle de Medicamentos e Entorpecentes , Lenalidomida/administração & dosagem , Talidomida/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/economia , Brasil , Análise Custo-Benefício , Custos de Medicamentos , Humanos , Lenalidomida/efeitos adversos , Lenalidomida/economia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/economia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Talidomida/efeitos adversos , Talidomida/economia , Resultado do Tratamento
5.
Eur J Pharm Sci ; 140: 105068, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518681

RESUMO

Maternofoetal physiologically-based pharmacokinetic models integrating multi-compartmental maternal and foetal units were developed using Simbiology® to estimate prenatal drug exposure. Processes governing drug disposition were described using differential equations with key system and drug-specific parameters. Transplacental drug transfer was modelled as bidirectional passive diffusion and benchmarked against those for thalidomide as a control. Model-predictions for pharmacokinetic parameters during pregnancy were within acceptable ranges for qualification (two-fold difference of clinically-observed values). Predicted foetal exposure to thalidomide was higher than efavirenz, with median (range) foetal-to-maternal plasma ratios of 4.55 (3.06-9.57) for 400 mg thalidomide versus 0.89 (0.73-1.05) for 400 mg efavirenz at third trimester. Model-predictions indicated foetal exposure consistently above 300% of maternal plasma concentration for thalidomide throughout pregnancy, while exposure to efavirenz increased from under 20% at second trimester to above 100% at third trimester. Further qualification of this approach as a tool in evaluating drug exposure and safety during pregnancy is warranted.


Assuntos
Benzoxazinas/farmacocinética , Simulação por Computador , Feto/efeitos dos fármacos , Modelos Biológicos , Talidomida/farmacocinética , Benzoxazinas/efeitos adversos , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Humanos , Absorção Intestinal , Permeabilidade , Placenta/metabolismo , Gravidez , Talidomida/efeitos adversos
6.
Saudi J Kidney Dis Transpl ; 30(4): 974-977, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464258

RESUMO

Thalidomide, which is an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, has regained value in the treatment of multiple myeloma. Serious pulmonary complications due to thalidomide use remain relatively uncommon. We describe a case of bronchiolitis obliterans organizing pneumonia (BOOP) due to thalidomide. A 51-year-old man with IgG lambda myeloma was treated with thalidomide and dexamethasone. Seven days after the beginning of chemotherapy, the patient presented a fever and a persistent cough. Auscultation revealed crackles in both pulmonary bases. The chest X-ray showed a diffuse bilateral alveolar-interstitial syndrome. Computed tomography scan revealed bilateral pulmonary involvement, with bilateral interstitial alveolar infiltration and ground-glass pattern consolidations. Pulmonary infection, malignant tumor, and lung involvement of multiple myeloma were excluded through various tests. Thalidomide-induced BOOP was suspected, and the drug was withdrawn and replaced by Melphalan. The patient had complete resolution of his symptoms and radiologic pulmonary involvement on discontinuation of the drug. In the absence of other etiologies, physicians should be cognizant of this potential complication in patients receiving thalidomide who present with respiratory symptoms.


Assuntos
Antineoplásicos/efeitos adversos , Pneumonia em Organização Criptogênica/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Talidomida/efeitos adversos , Antineoplásicos/administração & dosagem , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Substituição de Medicamentos , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Talidomida/administração & dosagem , Resultado do Tratamento
7.
Int J Hematol ; 110(4): 447-457, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325152

RESUMO

We conducted a phase I study to determine the recommended dose of thalidomide combined with melphalan plus prednisolone (MPT) and a phase II study evaluating the efficacy and safety of this MPT regimen in transplant-ineligible Japanese patients with untreated multiple myeloma. The recommended dose was determined to be 100 mg/day in the phase I study. In the phase II, randomized, double-blind, parallel-group study, patients were allocated to either MPT (n = 52) or MP (n = 51), with 21 and 29 patients completing the study, respectively. Overall response rate, the primary endpoint, was significantly higher in the MPT [40.4% (21/52 patients), 95% confidence interval (CI) 27.0-54.9%] than in the MP [19.6% (10/51 patients), 95% CI 9.8-33.1%] group (P = 0.022). Time to response was also significantly shorter in the MPT group. Incidences of hematological toxicities were similar in the two groups, suggesting that addition of thalidomide did not increase hematological toxicity. Although incidences of some non-hematological toxicities tended to be higher in the MPT group, the low incidence of ≥ Grade 3 toxicities suggests that MPT therapy was well tolerated. These results support the safety and efficacy of MPT therapy in untreated Japanese multiple myeloma patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Autoenxertos , Método Duplo-Cego , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Transplante de Células-Tronco , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
8.
Lancet Haematol ; 6(9): e459-e469, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327687

RESUMO

BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5-10·9). Median progression-free survival was 5·6 months (95% CI 3·7-7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05-2·22; p=0·98). Median overall survival was not reached (95% CI 12·9-not reached) versus 15·2 months (12·7-not reached; HR 1·61; 95% CI 0·91-2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Miocardite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Síndrome de Stevens-Johnson/etiologia , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
9.
J Med Case Rep ; 13(1): 175, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31174605

RESUMO

BACKGROUND: Inflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues still exist in this field. CASE PRESENTATION: We present the case of a 14-year-old Caucasian boy with refractory ulcerative colitis, admitted to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari in the course of his first-episode psychosis. He showed an acute onset of psychotic symptomatology during treatment with thalidomide, an immunomodulatory drug used in the experimental therapy of refractory inflammatory bowel disease. Thalidomide was discontinued and orally administered mesalazine was restarted. In addition, treatment with antipsychotics and mood stabilizers was introduced with gradual improvement of psychotic symptoms. According to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated after a 6-month follow-up. Throughout this period, both psychopharmacological and mesalazine-based gastrointestinal treatments were maintained with partial remission of psychiatric and gastrointestinal symptoms. CONCLUSIONS: We propose that refractory ulcerative colitis and psychosis might represent different manifestations of a common pathological pathway. However, it is also conceivable that thalidomide may have played a role in promoting the manifestation of psychotic symptoms in an individual with a specific vulnerability to schizoaffective disorders. Further investigations are needed to improve our knowledge regarding the complexity of brain-gut interactions, thus improving the management of co-existing inflammatory bowel and schizophrenia spectrum disorders.


Assuntos
Antipsicóticos/administração & dosagem , Colite Ulcerativa , Mesalamina/administração & dosagem , Transtornos Psicóticos , Talidomida , Adolescente , Assistência ao Convalescente , Idade de Início , Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Substituição de Medicamentos/métodos , Cuidado Periódico , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Neuroimunomodulação , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/imunologia , Indução de Remissão/métodos , Talidomida/administração & dosagem , Talidomida/efeitos adversos
10.
Expert Opin Drug Saf ; 18(6): 523-536, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31046481

RESUMO

INTRODUCTION: The management of psoriasis can include oral medications and injectable biologics. Safety data of these various treatment options are important to consider when choosing the right treatment for the patient. AREAS COVERED: This review evaluates the safety of newer treatments approved for psoriasis, including interleukin-(IL)-17 inhibitors, IL-23/p19 inhibitors, ustekinumab, certolizumab pegol and apremilast, using phases III and IV clinical trial data. EXPERT OPINION: Even as treatment of psoriasis becomes safer, it is important to recognize both common and uncommon adverse effects of treatment. Common adverse effects are similar across treatment options, including upper respiratory infection and injection-site reaction. Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast. While IL-23/p19 inhibitors may have a slightly better safety profile than other biologics, long-term data are limited. The conclusions that can be drawn from clinical trial safety data are limited given that many clinical trials are not large enough to detect rare safety events. Data from registries provide important complementary information on long-term safety but there are limitations including a lack of randomized assignment between drug treatments.


Assuntos
Produtos Biológicos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Administração Oral , Produtos Biológicos/efeitos adversos , Certolizumab Pegol/administração & dosagem , Certolizumab Pegol/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Humanos , Injeções , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
11.
Perspect Biol Med ; 62(1): 159-187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031303

RESUMO

Financial conflicts of interest can influence the design, conduct, and dissemination of medical trials. In attempting to resist "finance bias," critics and proponents of evidence-based medicine (EBM) and its precursors have largely focused on trying to improve evidence. These efforts have led to successes ranging from the 1962 Kefauver-Harris amendments to the US Federal Drug and Cosmetic Act of 1938 to recent recommendations that all trials be published. However, there are two problems with the strategy of trying to improve evidence as a buffer against finance bias. First, without political teeth, rules of evidence can be ignored with relative impunity. This is because, as sociologist Bent Flyvbjerg has pointed out, there is an asymmetry between power (of finance bias) and rationality (evidence), tending towards victory of power in an open confrontation. Second, by improving the way evidence is produced, the process has become more expensive, and thus more susceptible to influence by finance bias. Unless they address the powers behind finance bias directly, critics and proponents may be doomed to lose the war against finance bias, even if they win some battles. For EBM to be effective, the power of finance bias influencing the production and dissemination of evidence needs to be addressed as a priority. This is starting to happen, with initiatives such as the AllTrials campaign, which identifies and exposes unpublished trials. On the other hand, there are reasons to be less optimistic, as Cochrane, the most trusted source of evidence, has become more susceptible to stronger influences from industry.


Assuntos
Ensaios Clínicos como Assunto/economia , Medicina Baseada em Evidências/economia , Antiarrítmicos/efeitos adversos , Indústria Farmacêutica/economia , Humanos , Oseltamivir/efeitos adversos , Opinião Pública , Talidomida/efeitos adversos
12.
Indian J Pharmacol ; 51(1): 72-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031470

RESUMO

The distressing consequences of immunology in leprosy is the lepra reaction. Erythema nodosum leprosum(ENL) in special cases need to be managed with capsule thalidomide in varying doses. We report such a case of bradycardia in thalidomide dose dependent manner in a young ENL male.


Assuntos
Bradicardia/induzido quimicamente , Eritema Nodoso/tratamento farmacológico , Hansenostáticos/efeitos adversos , Hanseníase Virchowiana/tratamento farmacológico , Talidomida/efeitos adversos , Adulto , Relação Dose-Resposta a Droga , Humanos , Hansenostáticos/administração & dosagem , Masculino , Talidomida/administração & dosagem , Adulto Jovem
13.
BMC Womens Health ; 19(1): 51, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943953

RESUMO

BACKGROUND: Between 1957 and 1961 the substance Thalidomide was sold in West Germany and taken by many women as a sedative during pregnancy. This lead to miscarriages and infants been born with several severe malformations. The aim of this study was to describe the current situation of women impaired by Thalidomide induced embryopahty in North Rhine-Westphalia (Nordrhein-Westfalen), Germany, in comparison with the results found in a study done in 2002 by Nippert et al. METHODS: Questionnaires as well as examinations were performed. Data were compared using descriptive and inductive statistical methods. RESULTS: Both studies show that women impaired by Thalidomide embryopathy face a poorer health status than women their age in the general population and live in fear of further deteriorating health. The majority can only work reduced hours or are already retired due to poor health. Most of those who need assistance are being assisted by their social environment, while professional care is still utilized in only few cases. CONCLUSIONS: An obvious need for a shift in the provision of assistance and/or care provided was found as the social environment supporting the impaired women is also aging and therefore in high danger of breaking apart. TRIAL REGISTRATION: The study has been registered at German Clinical Trials Register, DRKS00010593 , on 07.06.2016 retrospectively.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Imunossupressores/efeitos adversos , Talidomida/efeitos adversos , Saúde da Mulher/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Doenças Fetais/epidemiologia , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
14.
Hautarzt ; 70(5): 354-362, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30937481

RESUMO

Apremilast is an oral inhibitor of phosphodiesterase-4 (PDE4) that is licensed for the second-line treatment of psoriasis and psoriatic arthritis. Data from several phase III clinical trials and real-world studies showed a good benefit-risk profile, with diarrhea and nausea as the most common adverse events. Diarrhea and nausea most frequently occurred during the first month of treatment. In most cases, they were mild or moderate in severity and tended to resolve over time with continued dosing and without intervention. In this review we summarize available data on gastrointestinal side effects of apremilast in patients with psoriasis and psoriasis arthritis and provide practical strategies for managing these symptoms.


Assuntos
Anti-Inflamatórios não Esteroides , Artrite Psoriásica , Gastroenteropatias , Inibidores da Fosfodiesterase 4 , Psoríase , Talidomida/análogos & derivados , Anti-Inflamatórios não Esteroides/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Gastroenteropatias/induzido quimicamente , Humanos , Psoríase/tratamento farmacológico , Talidomida/efeitos adversos
16.
Rev Soc Bras Med Trop ; 52: e20180385, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30994805

RESUMO

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.


Assuntos
Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Talidomida/efeitos adversos , Estudos Transversais , Escolaridade , Feminino , Humanos , Hansenostáticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Talidomida/uso terapêutico
17.
Dermatol Ther ; 32(4): e12923, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30977956

RESUMO

There are limited treatment options available to control the progression of vitiligo and most of these treatment options carry the risk of both short-term as well as long-term adverse effects. Apremilast has emerged as a promising treatment option in psoriasis and many other cutaneous disorders. We report herein the successful use of oral apremilast therapy in controlling the progression of adult onset vitiligo in 13 patients. The patients had not responded to other systemic treatments earlier. In addition to the control of progression, eight patients (61.5%) showed some evidence of repigmentation after apremilast therapy. Gastrointestinal adverse effects and headache were the commonest adverse effects reported that led to cessation of treatment in two cases.


Assuntos
Inibidores da Fosfodiesterase 4/uso terapêutico , Talidomida/análogos & derivados , Vitiligo/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Talidomida/efeitos adversos , Talidomida/uso terapêutico
18.
Dermatol Ther ; 32(4): e12946, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31025500

RESUMO

Acrodermatitis continua of Hallopeau (ACH) is a chronic, inflammatory, and relapsing disorder characterized by the progressive destruction of fingernails and toenails. This condition is rare, difficult to treat, and often misdiagnosed. Several antipsoriatic treatments have been used, without any therapeutic guideline and no real improvement. Apremilast is an oral phosphodiesterase 4 inhibitor, approved for the treatment of chronic plaque psoriasis and psoriatic arthritis. It increases the intracellular concentration of cAMP and restores cytokine equilibrium, especially IL-10, which is particularly involved in nail psoriasis. We reported the case of a 58-year-old man affected by ACH, successfully treated with Apremilast, who achieved a complete healing in just 1 month of treatment without any side effect. We suggest this drug as a successful new treatment for ACH, which can improve clinical manifestations rapidly and has no or few adverse effects. Future formal clinical trials and additional case reports are needed to establish the safety and efficacy of Apremilast in the treatment of ACH.


Assuntos
Acrodermatite/tratamento farmacológico , Doenças da Unha/tratamento farmacológico , Talidomida/análogos & derivados , Acrodermatite/patologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/patologia , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do Tratamento
19.
J Int Med Res ; 47(5): 2228-2233, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30832535

RESUMO

Thalidomide is effective in inducing and maintaining clinical remission, as well as mucosal healing, in patients with refractory Crohn's disease (CD). However, long-term use of thalidomide has raised concern because of the high incidence of adverse events. Cardiovascular events induced by thalidomide have been reported in patients with multiple myeloma, amyotrophic lateral sclerosis, and transfusion-dependent refractory anemia. We report here an extremely rare case of sinus bradycardia induced by thalidomide in an adult patient with CD. This patient's heart rate converted back to a normal sinus rhythm after withdrawal of thalidomide, but recurred after restarting of thalidomide. Cardiac toxicity should be closely monitored when using thalidomide in patients with CD.


Assuntos
Bradicardia/induzido quimicamente , Bradicardia/complicações , Seio Coronário/patologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Adulto , Bradicardia/fisiopatologia , Frequência Cardíaca , Humanos , Mucosa Intestinal/patologia , Masculino
20.
Blood ; 134(2): 123-133, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862646

RESUMO

This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 patients (42%) remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados
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