Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial.

BACKGROUND: A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). AIM: To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. METHODS: Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300-500 µm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. RESULTS: Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months--not reached); the median overall survival was 24.5 months (95% CI 14.7 months--not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly. CONCLUSIONS: Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).