Formation of multiple pulmonary nodules during treatment with leflunomide / Formação de múltiplos nódulos pulmonares durante tratamento com leflunomida

Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis and can be due to the disease itself or secondary to the medications used in order to treat it. We report the case of a 60-year-old woman who had been diagnosed with rheumatoid arthritis and developed multiple pulmonary nodules during treatment with leflunomide.

O comprometimento pulmonar é uma das manifestações extra-articulares da artrite reumatóide e pode ser devido à própria doença ou secundário às medicações utilizadas para seu tratamento. Este trabalho relata um caso de uma paciente de 60 anos de idade com diagnóstico de artrite reumatoide que evoluiu com múltiplos nódulos pulmonares durante o tratamento com leflunomida.

Alopecia universalis during treatment with leflunomide and adalimumab - Case report

Alopecia areata is a non-scarring form of alopecia that can be localized or widespread. Its etiology is unknown, but immunological factors are implicated in its pathogenesis. With the more frequent use of anti TNFα biologic drugs, some alopecia areata cases during their use have been described. We report a case of universal alopecia in a patient with rheumatoid arthritis while using adalimumab and leflunomide.

Leucopenia grave em paciente com artrite reumatoide tratada com combinação de metotrexato e leflunomida / Severe leukopenia in a rheumatoid arthritis patient treated with a methotrexate/leflunomide combination

Apresentamos o caso de uma paciente com artrite reumatoide tratada por dois anos com associação de metotrexato e leflunomida. A paciente foi internada com leucopenia grave quatro semanas após acrescentar ao esquema medicamentoso as drogas clopidogrel, isosorbida, sinvastatina, AAS e omeprazol.

A rheumatoid arthritis patient was treated for two years with methotrexate and leflunomide combination therapy. The evolution was uneventful until she had clopidogrel, simvastatin, isosorbide, aspirin and omeprazole added to medication due to acute myocardial infarction. Four weeks after this, she was hospitalized with severe leukopenia.

Eficácia terapêutica e segurança de metotrexato + leflunomida em pacientes colombianos com artrite reumatoide ativa refratária ao tratamento convencional / Therapeutic efficacy and safety of methotrexate + leflunomide in Colombian patients with active rheumatoid arthritis refractory to conventional treatment

INTRODUÇÃO: A combinação de metotrexato (MTX) + leflunomida (LFN) demonstrou ser efetiva no tratamento da artrite reumatoide (AR), mas sua segurança tem sido questionada. OBJETIVO: Avaliar a eficácia e a segurança terapêutica da combinação de MTX + LFN em pacientes com AR ativa. MÉTODOS: Estudo multicêntrico com 24 semanas de duração envolvendo 88 pacientes com doença ativa, apesar do tratamento regular com MTX e prednisolona. RESULTADOS: Participaram do estudo 78 mulheres (88%) e 10 homens. A idade foi de 51,3 ± 12,4 anos, e o tempo de evolução da doença, 8,0 ± 6,8 anos. Os pacientes tinham doença ativa evidenciada por IQR média de 10 (7,0-13,0) nas articulações inflamadas e 14,0 (18,0-10,0) nas articulações dolorosas. As respostas ACR obtidas na semana 24 foram: ACR20: 76%; ACR50: 67,1%; e ACR70: 23,9%. Houve melhora na atividade da doença, medida pelo escore DAS-28: 5,8 ± 1,2 no início do estudo vs. 3,8 ± 1,6 na semana 24 (P = 0,000). O evento adverso mais significativo foi elevação das transaminases, ocorrida em oito (26%) pacientes. Oito pacientes descontinuaram o estudo devido a eventos adversos: quatro por elevação das transaminases, um por diabetes insípido, um por erupção cutânea, um por diabetes mellitus e um por dor osteomuscular. CONCLUSÃO: A combinação de MTX + LFN é efetiva para o tratamento de AR em pacientes que não obtiveram sucesso com o tratamento convencional. Há necessidade de rígido controle médico e laboratorial para segurança terapêutica.

INTRODUCTION: The combination of methotrexate (MTX) + leflunomide (LFN) has been shown to be effective in the treatment of RA. Its safety has been questioned. OBJECTIVE: To evaluate the effectiveness and safety of the combination of MTX + LFN in patients with active RA. METHODS: This was a 24-week multicenter study, which included 88 patients with active disease despite consistent treatment with methotrexate and prednisolone. RESULTS: We included 78 women (88%) and 10 men. The age was 51.3 ± 12.4 years, and the evolution of disease was 8 ± 6.8 years. Patients had active disease, which was indicated by a median of IQR of 10.0 (7.0-13.0) for swollen and of 14.0 (18.0-10.0) for tender joints for the whole group. The ACR responses achieved at week 24 were: ACR20: 76.0%; ACR50: 67.1%; ACR70: 23.9%. There was improvement in the activity of disease: DAS-28 score: 5.8 ± 1.2 at baseline vs. 3.8 ± 1.6 at week 24 (P = 0.000). The most significant adverse event was elevation of transaminases in eight patients (26%). Eight patients were withdrawn due to adverse events: four due to the elevation of transaminases, and one each due to diabetes insipidus, rash, diabetes mellitus and osteomuscular pain. CONCLUSION: The combination of MTX + LFN is effective for treating RA in patients for whom conventional treatment has failed. Strict medical and laboratory control is to be enforced for safety.

Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone) compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews / Eficácia e segurança dos antipsicóticos atípicos (quetiapina, risperidona, aripiprazol, paliperidona) em comparação com um placebo ou medicamentos antipsicóticos típicos no tratamento da esquizofrenia refratária: overview de revisão sistemática

CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20-40 percent. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline) (1966-2009), Controlled Trials of the Cochrane Collaboration (2009, Issue 2), Embase (Excerpta Medica) (1980-2009), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

CONTEXTO E OBJETIVO: De acordo com alguns estudos de coorte, a prevalência da esquizofrenia refratária (ER) está entre 20-40 por cento. Nosso objetivo foi avaliar a efetividade e segurança de aripiprazol, paliperidona, quetiapina e risperidona no tratamento da esquizofrenia refratária. MÉTODOS: Avaliação crítica das revisões Cochrane publicadas na Biblioteca Cochrane e complementação com referências de ensaios clínicos randomizados (ECRs) mais atualizados sobre ER. As seguintes bases de dados foram pesquisadas: Medline (Medical Literature Analysis and Retrieval System Online) (1966-2009), Ensaios Controlados da Colaboração Cochrane (2009, edição 2), Embase (Excerpta Database) (1980-2009), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) (1982-2009). Não houve restrição a idiomas. Ensaios clínicos randomizados, revisões sistemáticas e metanálises que avaliaram antipsicóticos atípicos no tratamento da esquizofrenia refratária foram incluídos. RESULTADOS: Sete revisões sistemáticas Cochrane e 10 ECRs complementares foram incluídos nessa revisão. No geral os dados demonstram pequenas diferenças entre os antipsicóticos atípicos avaliados e os típicos na melhora dos sintomas da doença, apesar da melhor adesão ao tratamento com os atípicos. A risperidona foi avaliada especificamente em pacientes com esquizofrenia refratária em uma das revisões sistemáticas incluídas, a qual demonstrou desfechos favoráveis, porém não definitivos quando comparada a drogas também com eficácia comprovada como amisulprida, clozapina e olanzapina. CONCLUSÕES: Os dados reforçam a dificuldade de tratar esses pacientes, com elevadas taxas de desistência do tratamento e padrões de melhora modestos nas avaliações de eficácia. Os antipsicóticos atípicos têm vantagens sobre os típicos principalmente pelo melhor perfil de segurança, o que leva a melhor adesão ao tratamento. A associação de antipsicóticos também pode ser uma opção em alguns pacientes refratários ao tratamento.

Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis patients who develop refractoriness are left with no alternatives other than leflunomide and costly biological response modifiers. Leflunomide, though effective, was associated with adverse events and has not been extensively studied in the Indian population. AIMS: Determination of safety and efficacy of leflunomide alone and if not useful, in combination with methotrexate in patients refractory to conventional disease-modifying agents. SETTING AND DESIGN: Open labeled clinical trial with leflunomide [100 mg, OD x 3 days followed by 20 mg, OD x 6 months], if no improvement at three months, combined with methotrexate [5-7.5 mg, OD x 3 months] at a tertiary care hospital. MATERIALS AND METHODS: The primary endpoint in the improvement in EULAR criteria and secondary endpoints were patient and physician global evaluation, incidence of remission and biochemical and clinical adverse events. STATISTICAL ANALYSIS: Chi square test or Fisher's exact test and parametric and non-parametric repeat measure ANOVA were used for analysis. RESULTS: Among 84 patients who were included in the study, leflunomide showed improvement and remission in 52 [62%] and 6 [7%] in six months, by intention to treat analysis. Adverse events were observed in 15, discontinuation in 5 and 24 dropped out. With combination in 11 patients, there was improvement and remission in nine [91%] and one [9%] after three months. Adverse events were observed in six and one discontinued. CONCLUSIONS: If regular monitoring of hepatic function and hematological parameters are performed, leflunomide is an effective and safe drug in the Indian population in resistant rheumatoid arthritis patients, especially if used alone.

Severe cutaneous adverse drug reaction to leflunomide: a report of five cases.

Medications used to treat human ailments are known to cause cutaneous reactions which may vary in their severity. Leflunomide, an immunomodulating agent recently introduced to treat rheumatoid arthritis, is reported to cause severe cutaneous reactions. We are reporting five such cases. All our patients were started on leflunomide for rheumatoid arthritis, 4-6 weeks before the onset of cutaneous reaction and were admitted to the hospital with the common complaints of fever, skin rash and generalized weakness. All of them had characteristic pattern of events such as delayed onset of reaction, widespread and long lasting skin rash and internal organ involvement. These features suggest a possibility of drug hypersensitivity syndrome to leflunomide. Careful dosing and periodic monitoring of patients treated with leflunomide for possible adverse drug reaction is recommended.

Necrolisis tóxica epidérmica: caso clínico / Toxic epidermal necrolysis: clinical case

Toxic epidermal necrolysis is a potentially fatal disease due to allergic reactions to drugs. We report on a 58 years old female, that presented Raynaud sphenomenon during 20 years. During the last year, she developed polyarthritis of hands, shoulders, knees and ankles. Rheumatoid factor (RF), antinuclear antibodies (ANA) and U_ ribonucleoprotein (U1 RNP) were present, and Mixed connective tissue disease was suspected. Because of a poor response to methotrexate the patient received leflunomide. Two weeks later, she began with fever, pruritus and generalized edema. Within days this affected her neck, thorax, eyes and oral mucous. She had bullaes and areas of epidermic detachment. A toxic epidermal necrolysis was diagnosed and treated with IV immunoglobulins. The lesions disappeared successfully. In addition to the dermatological problem, the patient later presented ocular complications that required the transplant of both corneal, with the sub-sequent loss of one of her eyes.

Efficacy and safety of the first parenteral selective COX-2 inhibitor, parecoxib sodium, in adult patients with postoperative pain.

Parecoxib, a prodrug of valdecoxib, a selective COX-2 inhibitor, has been recently introduced for the treatment of moderate to severe postoperative pain. This prospective, open, multicentric study enrolled 260 patients undergoing orthopaedic, gynaecological, dental and general surgery. Postoperatively, patients were treated with parecoxib, 40 mg IM/IV. There was a statistically significant decrease in the mean pain intensity score (p<0.05). At the end of 24 hours, 89.6% of total cases had a very good to total relief of pain. The mean duration of analgesia was 19.26 hours and mean time of onset of analgesia was 16.25 minutes ranging from 11-20 minutes. The laboratory values were within normal limits. The drug was well tolerated. There was no report of any hypersensitivity reaction. This study suggests that parecoxib, in a dose of 40 mg IM/IV, is an effective and safe option for the management of postoperative pain.

New antiepileptic drugs. II. Clinical use

No abstract available.