Anti-TNFα and tuberculosis

Les anti-TNFα sont très efficaces dans le traitement des maladies inflammatoires chroniques rhumatismales et intestinales mais exposent à un risque élevé d’infections opportunistes, en particulier la tuberculose. Ce risque est multiplié par 2 à 10 chez les patients sous anti-TNFα par rapport à la population générale et par 2 à 4 par rapport aux malades sans anti-anti-TNFα. Il s’agit le plus souvent de tuberculoses extrapulmonaires et de formes disséminées. Ces tuberculoses surviennent au cours de la première année de traitement et correspondent dans la majorité des cas à une réactivation de tuberculose latente ; d’où la mise en place de recommandations de dépistage et de prévention. Outre l’anamnèse, l’examen physique et la radiographie du thorax, la recherche d’une tuberculose latente repose aussi sur l’intradermoréaction à la tuberculine (IDR). Mais celle-ci présente certaines limites surtout chez ces malades immunodéprimés (faux négatifs) ou vaccinés par le BCG (faux positifs). Les tests de relargage de l’interféron-γ : IGRA (Interferon-Gamma Release Assays) semblent être plus sensibles et plus spécifiques et devraient être utilisés dans cette indication. La prophylaxie repose sur l’isoniaside seul pendant 9 mois ou l’association isoniazide-rifampicine pendant 3 mois). Elle doit être débutée au moins 3 semaines avant la première cure d’anti-TNFα. Ces stratégies se sont révélées efficaces en diminuant nettement le nombre de tuberculoses sous anti-TNFα en les ramenant aux taux avant anti-TNFα.Anti-TNFα is a very effective treatment of the rheumatic and intestinal chronic inflammatory diseases but exposes to a high risk of opportunist infections, in particular tuberculosis. This risk increases twofold to tenfold when compared to the general population and by 2 to 4 when compared to the same patients without anti-TNFα. Non-pulmonary and disseminated tuberculosis are the most frequent forms with anti-TNFα. Tuberculosis arises during the first year of treatment and corresponds in most cases to a reactivation of latent tuberculosis; hence the implantation of recommendations of screening and prevention. Besides anamnesis, physical examination and chest radiograph, screening for latent tuberculosis also relies on the tuberculin skin test (TST). But this presents limitations especially in immunosuppressed patients (false negative) or in BCG-vaccinated patients (false-positive). The tests for Interferon-Gamma Release Assays (IGRA) seem to be more sensitive and more specific and should be used in this indication. Chemoprophylaxis is based on the use of isoniaside alone during 9 months or the isoniaside-rifampicine association during 3 months. It has to be started at least 3 weeks before the first cure of anti-TNFα. These strategies have shown to be effective by clearly decreasing the number of tuberculosis cases under anti-TNFα treatment to a rate similar to what observed before anti-TNFα treatment

Response to Pegylated Interferon in Chronic Hepatitis B, Effect of with and without Precore Mutant Stain: A Multicenter Tunisian Study

Background and Study Aims: To evaluate the effectiveness of pegylated interferon in patients with chronic hepatitis B infection in a real life setting.Patients and Methods: Fifteen hospitals in Tunisia were included in this study. Data from consecutively treated chronic hepatitis B (CHB) patients, who received pegylated interferon, were collected retrospectively. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Sustained virologic response (SVR) is defined as an hepatitis B virus (HBV) DNA concentration of less than 2,000 IU/mL six months after the completion of therapy.Results: A total of 351 CHB patients under peg interferon alfa-2a treatment were included in this multicenter, open label, non-interventional study.Thirty five HBeAg positive patients were identified (62% male, 23% advanced fibrosis). Six months after therapy, 24% had viral loads < 2000 IU/mL, 20% achieved HBeAg seroconversion and 5, 7% achieved HBs Ag loss.Three hundreds sixteen HBeAg negative patients were treated (72, 5% male, 24% advanced fibrosis). Six months post-treatment, 14 % had viral loads < 2000 IU/mL and 1, 2% achieved HBs Ag loss.Treatment was well tolerated in 92% of cases and was stopped in 5.2% of patients.In multivariate analysis, predictors of response to pegylated interferon were: age less than 50 years (P=0,04 IC [0,169-0,737]), precore mutant stain infection (p=0,04 IC [0,60-0,69]), a body mass index < 30kg/m2 (P=0,05 IC [0,225-0,320]), and a pre-treatment serum HBV DNA level <20000IU/ml (P=0,03 IC [1,316-2,225]).Conclusion: PEG-IFN therapy in chronic hepatitis B (CHB) is well tolerated and can achieve a good response especially if we select good responders