July News

Kay Downer

ITPA Polymorphisms Predict Outcomes in HIV/HCV Co-Infected Patients

Previous research has shown that single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene are associated with hemolytic anemia in hepatitis C virus (HCV)-infected patients who are receiving peginterferon and ribavirin therapy. In a recent study in the July issue of the Journal of Medical Virology, Osinusi and colleagues confirmed the association between ITPA polymorphisms and hemoglobin decline in a population that included 58 patients infected with HCV and 63 patients co-infected with HIV and HCV. Genotyping for the rs1127354 and rs7270101 SNPs revealed that 30% of patients (n=35) were predicted to have reduced ITPA activity. The severity of ITPA deficiency was inversely correlated with the rates of hemoglobin reduction greater than 3 g/dL during treatment with peginterferon and ribavirin. Among HIV/HCV co-infected patients, ITPA deficiency was not only associated with slower hemoglobin decline by Week 4 (P=.020) but was also associated with rapid virologic response at Week 4 (P=.017).

Comparison of Medical, Endoscopic, and Surgical Therapies for Patients with Chronic Pancreatitis 

To determine the efficacy of endoscopic therapy for the treatment of chronic pancreatitis, Clarke and coauthors analyzed data from 146 patients enrolled in the NAPS2 study; this retrospective analysis was published in the July issue of Clinical Gastroenterology and Hepatology. Among symptomatic patients who received medical therapy, 31% showed improvement over a mean follow-up period of 5.7 years, while 53% of patients showed no change in symptoms; among the latter group, 21% subsequently underwent surgery. Among patients who received endoscopic therapy, 51% met the criteria for clinical success (cessation of narcotic therapy and resolution of acute pancreatitis episodes). Clinical success was also achieved in 50% of patients who received endoscopic therapy and subsequently underwent surgery.

Factors associated with successful endoscopic therapy included older age, shorter duration of disease before endoscopic therapy, less constant pain, and lower daily narcotics requirement. Based on these findings, Clarke and colleagues proposed that management of chronic pancreatitis should begin with medical therapy, but clinicians should consider early endoscopic therapy based on the presence of symptoms and certain morphologic features. Surgical intervention should be considered based on an individualized assessment of risks and benefits.

Long-Term Safety Analysis of Adalimumab Shows No New Safety Signals 

Anti–tumor necrosis factor drugs are known to increase the risk of serious infections, and the mechanism of action of these drugs suggests that malignancy is also a possible concern. To evaluate these risks, Burmester and colleagues analyzed data from 71 clinical trials of adalimumab (Humira, Abbott); results of this study were published online ahead of print in the Annals of the Rheumatic Diseases. This safety analysis included a total of 23,458 patients with rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn’s disease (CD); together, these patients had 36,730.5 person-years of drug exposure.

Calculation of standardized incidence ratios revealed that serious infections were the most frequent serious adverse event associated with adalimumab; the incidence rate of serious infections among CD patients was
6.7 events per 100 person-years. In terms of malignancies, CD patients experienced malignancies (excluding lymphoma and nonmelanoma skin cancer) at an incidence rate of 0.5 events per 100 person-years; however, the observed number of malignancies in this group was similar to the expected number of malignancies in the general population. Finally, the risk of mortality for patients treated with adalimumab was not increased compared to the general population.

In BriefA pooled safety analysis of over 2,000 patients found that use of infliximab (Remicade, Janssen Biotech) for the treatment of inflammatory bowel disease did not increase the incidence of infection, malignancy, or mortality. Am J Gastroenterol. 2012 May 22. Epub ahead of print.

A report of 5 studies of entecavir (Baraclude, Bristol-Myers Squibb) and 2 studies of tenofovir disoproxil fumarate (Viread, Gilead) confirmed that both drugs show high rates of virologic response, low incidences of resistance, and good tolerability when used in a real-world clinical setting for the treatment of hepatitis B virus. J Viral Hepat. 2012;19:377-386.

Millennium Medical Publishing, Inc