Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Incidence and risk factors associated with hepatocellular carcinoma surveillance failure.

BACKGROUND AND AIM: Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure. METHODS: The study analyzed data from 188 consecutive patients diagnosed with HCC within a surveillance program conducted among 1,242 cirrhotic patients and based on ultrasonography and alpha-fetoprotein (AFP) testing every 3 or 6 months. Program failure was defined as the detection of HCC exceeding the Milan criteria. Variables recorded at entry into the program, during follow-up and at HCC diagnosis, were analyzed. RESULTS: At diagnosis, 50 (26.6%) HCC tumors were beyond the Milan criteria. In univariate analysis, Child-Pugh B at entry (P = 0.03), development of complications of portal hypertension before tumor diagnosis (P = 0.03), and failure to complete the prior screening round (P = 0.02), Child-Pugh B/C (P = 0.001) and AFP ≥ 100 ng/mL (P = 0.03) at diagnosis, were associated with failure. In multivariate analysis, only Child-Pugh B/C (hazard ratio, 3.18; 95% confidence interval, 1.66-6.10, P < 0.001) and AFP ≥ 100 ng/mL, both at diagnosis (hazard ratio, 2.80; 95% confidence interval, 1.37-5.71, P = 0.005), were independently associated with failure. Survival was higher among patients with tumors within the Milan criteria than those with program failure (33.9 vs 7.6 months, P < 0.001). CONCLUSIONS: Approximately 25% of HCC cases diagnosed among patients included in a surveillance program were beyond the Milan criteria. Child-Pugh B/C and AFP ≥ 100 ng/mL at diagnosis were associated with program failure. However, Child-Pugh B at entry and development of liver-related complications during follow-up can be early predictors of failure.

Adherence to a Semiannual Surveillance Program for Hepatocellular Carcinoma in Patients With Liver Cirrhosis.

BACKGROUND: Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis. MATERIALS AND METHODS: A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds. RESULTS: Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant. CONCLUSIONS: The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.

Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups.

BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) and associated risk factors in patients with alcoholic cirrhosis are not well defined. Surveillance for HCC among patients with cirrhosis who do not have hepatitis B is cost effective only if the expected risk of HCC exceeds 1.5% per year. We performed a prospective study to determine the incidence of HCC among patients with alcoholic cirrhosis and to identify risk factors. METHODS: We analyzed data from a surveillance program of 450 patients, aged 40 to 75 years, with alcoholic cirrhosis of Child-Pugh class A or B; patients were enrolled at the liver unit of a tertiary center from September 1992 through March 2010. Data were collected on 20 demographic, clinical, and laboratory variables at the start of the study. Patients were examined every 3 to 6 months for 5 years to identify risk factors for HCC; incidence was determined from a median follow-up time of 42 months. RESULTS: Over the follow-up period, 62 patients developed HCC (43 in the first 5 y of follow-up evaluation), with an annual incidence of 2.6%. By using multivariate analysis, age 55 years and older (hazard ratio, 2.39; 95% confidence interval, 1.27-4.51) and platelet counts less than 125 × 10(3)/mm(3) (hazard ratio, 3.29; 95% confidence interval, 1.39-7.85) were associated independently with the development of HCC. These variables were used to define 3 risk groups. The annual incidence of HCC in the group without either of these factors was 0.3% (n = 93), the annual incidence with 1 factor was 2.6% (n = 228), and the annual incidence with both factors was 4.8% (n = 129) (P < .0001). CONCLUSIONS: The annual incidence of HCC among patients with alcoholic cirrhosis of Child-Pugh class A or B is around 2.5%. Age and platelet count can be used to classify the patients in 3 different risk groups for HCC development within the next 5 years.

[Luetic hepatitis. An emerging entity]. / Hepatitis luética. Una entidad emergente.

Liver involvement is unusual in the course of syphilitic infection. We present four cases of luetic hepatitis diagnosed at our hospital in the last 5 years. One patient was coinfected with hepatitis B virus and another patient was coinfected with hepatitis C virus and HIV. The presence of maculopapular skin lesions in palmoplantar distribution, as well as serological confirmation, were decisive for the diagnosis of syphilitic hepatitis, allowing early antibiotic therapy to be established, with clinical and analytical improvement in all patients. Luetic hepatitis should be considered in patients with risky sexual behavior, skin lesions and altered liver function tests with a predominance of cholestasis, despite the finding of other, more frequent, liver diseases, given that these entities may be concurrent. Early diagnosis of syphilis leads to effective treatment of the patient and to epidemiological control of the infection.

Hepatitis luética. Una entidad emergente / Luetic hepatitis. An emerging entity

La afectación hepática por sífilis es infrecuente. Se exponen 4 casos de hepatitis luética diagnosticados en los últimos 5 años. Uno presentaba coinfección por virus de la inmunodeficiencia humana y virus de la hepatitis C, y otro por virus de la hepatitis B. Las lesiones cutáneas maculopapulosas de extensión palmoplantar y la confirmación serológica fueron determinantes para llegar al diagnóstico. Ante el aumento de incidencia de las enfermedades de transmisión sexual, entre ellas la sífilis, es importante tener en cuenta el diagnóstico de hepatitis luética en aquellos pacientes que presentan hábitos sexuales de riesgo y alteración de pruebas de función hepática con predominio de colestasis, y no conviene descartarla a pesar del hallazgo de otras enfermedades hepáticas más frecuentes, dado que pueden coexistir. El diagnóstico precoz de la sífilis conduce a un tratamiento eficaz para el individuo y para el control epidemiológico de la infección(AU)

Liver involvement is unusual in the course of syphilitic infection. We present four cases of luetic hepatitis diagnosed at our hospital in the last 5 years. One patient was coinfected with hepatitis B virus and another patient was coinfected with hepatitis C virus and HIV. The presence of maculopapular skin lesions in palmoplantar distribution, as well as serological confirmation, were decisive for the diagnosis of syphilitic hepatitis, allowing early antibiotic therapy to be established, with clinical and analytical improvement in all patients. Luetic hepatitis should be considered in patients with risky sexual behavior, skin lesions and altered liver function tests with a predominance of cholestasis, despite the finding of other, more frequent, liver diseases, given that these entities may be concurrent. Early diagnosis of syphilis leads to effective treatment of the patient and to epidemiological control of the infection(AU)