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Clamart, France

Baughman R.P.,University of Cincinnati | Nunes H.,Service de pneumologie
Expert Review of Clinical Immunology | Year: 2012

The options for treatment of sarcoidosis have expanded. In this article, we outline a stepwise approach to treatment. Recommendations for treatment are based on available evidence. While corticosteroids remain the treatment of choice for initial systemic therapy, other agents have been shown to be steroid sparing, and therefore useful for long-term management. In addition, new agents have proved to be useful for patients with refractory disease. Source


Baughman R.P.,University of Cincinnati | Nunes H.,Service de pneumologie | Sweiss N.J.,University of Illinois at Chicago | Lower E.E.,University of Cincinnati
European Respiratory Journal | Year: 2013

The treatment options for pulmonary sarcoidosis have increased over the past 10 years. As new treatments have been introduced, the best way to assess and compare treatments remains unknown. The goal of this review is to discuss the standard treatments for pulmonary sarcoidosis, including glucocorticoids, and cytotoxic agents, such as methotrexate, azathioprine and leflunomide, and compare them to the newer biological agents, such as infliximab and adalimumab. We also discuss some novel treatments which are currently being evaluated. To compare these different regimens, we look at the measures used to assess response. These include pulmonary function, chest imaging, steroid sparing potential and, more recently, improvements in quality of life measures. While there is, as yet, no standard assessment for response, there is a growing consensus that response to treatment may include improvement of one or more of the following: forced vital capacity, chest imaging and steroid sparing. Several drugs used for pulmonary sarcoidosis have demonstrated improvement in one or more of these measures. Copyright©ERS 2013. Source


Janne P.A.,Belfer Institute for Applied Cancer Science | Shaw A.T.,Massachusetts General Hospital | Pereira J.R.,Instituto Brasileiro Of Cancerologia Toracica | Jeannin G.,Service de pneumologie | And 8 more authors.
The Lancet Oncology | Year: 2013

Background: No targeted therapies are available for KRAS-mutant non-small-cell lung cancer (NSCLC). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC. Methods: Eligible patients were older than 18 years of age; had histologically or cytologically confirmed stage IIIB-IV KRAS-mutant NSCLC; had failed first-line therapy for advanced NSCLC; had WHO performance status of 0-1; had not received previous therapy with either a MEK inhibitor or docetaxel; and had adequate bone marrow, renal, and liver function. Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m2 on day 1 of a 21 day cycle). Randomisation was done with an interactive voice response system and investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival, analysed for all patients with confirmed KRAS mutations. This study is registered with ClinicalTrials.gov, number NCT00890825. Findings: Between April 20, 2009, and June 30, 2010, we randomly assigned 44 patients to receive selumetinib and docetaxel (selumetinib group) and 43 to receive placebo and docetaxel (placebo group). Of these, one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive. Median overall survival was 9·4 months (6·8-13·6) in the selumetinib group and 5·2 months (95% CI 3·8-non-calculable) in the placebo group (hazard ratio [HR] for death 0·80, 80% CI 0·56-1·14; one-sided p=0·21). Median progression-free survival was 5·3 months (4·6-6·4) in the selumetinib group and 2·1 months (95% CI 1·4-3·7) in the placebo group (HR for progression 0·58, 80% CI 0·42-0·79; one-sided p=0·014). 16 (37%) patients in the selumetinib group and none in the placebo group had an objective response (p<0·0001). Adverse events of grade 3 or higher occurred in 36 (82%) patients in the selumetinib group and 28 (67%) patients in the placebo group. The most common grade 3-4 adverse events were neutropenia (29 [67%] of 43 patients in the selumetinib group vs 23 [55%] of 42 patients in the placebo group), febrile neutropenia (eight [18%] of 44 patients in the selumetinib group vs none in the placebo group), dyspnoea (one [2%] of 44 patients in the selumetinib group vs five [12%] of 42 in the placebo group), and asthenia (four [9%] of 44 patients in the selumetinib group vs none in the placebo group). Interpretation: Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC. Funding: AstraZeneca. © 2013 Elsevier Ltd. Source


Fraisse P.,Service de pneumologie
Revue des Maladies Respiratoires | Year: 2012

Latent tuberculosis infection is a key stage in the natural history of tuberculosis, and provides an important period where strategies to prevent the development of disease may be implemented. The treatment of latent tuberculosis infection is well described in many national guidelines. In this review, we attempt to help pneumonologists to implement these guidelines accurately and appropriately, prescribing preventive treatment when the benefitrisk ratio is optimal, providing treatment most safely, performing therapeutic education and incorporating preventive treatment into the full array of measures against tuberculosis. © 2012 SPLF. Source


Latent tuberculosis infection is a pathophysiological and clinical entity. The diagnosis is based on immunological tests such as the tuberculin skin test or interferon-gamma release assays. Interpretation of the results depends on the clinical context. Their predictive value for the occurrence of tuberculous disease is low, except in the case of young children and immunocompromised patients. Guidelines for the diagnosis of latent tuberculous infection in different countries are reviewed. The development of more predictive tests is desirable. © 2011 SPLF. Source

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