June 12, 2013

Telaprevir-based triple-drug therapy benefits CHC patients with ESRD

By: SHARON WORCESTER, Internal Medicine News Digital Network

06/10/13

ORLANDO – Triple-drug therapy with the protease inhibitor telaprevir plus ribavirin and peg-interferon alpha 2a provides higher sustained virologic response than traditional dual-drug therapy in chronic hepatitis C patients on hemodialysis, according to findings from the randomized, placebo-controlled Target C Trial.

Sustained virologic response after 24 months was 63% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin and peg-IFN alpha 2a for weeks 0-24 (group A) and 50% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin for weeks 13-36 and peg-IFN alpha 2a for weeks 0-36 (group B), compared with 25% in 12 patients treated with placebo plus standard dual therapy with ribavirin and peg-IFN alpha 2a for weeks 0-24 and weeks 37-48 (group C, reference arm), Dr. Patrick Basu reported at the annual Digestive Disease Week.

Telaprevir in groups A and B was given as two 750-mg tablets three times daily for 4 days and three 750-mg tablets given twice daily for 3 days after dialysis. The ribavirin dose in group A was 200 mg for weeks 0-12 and 400 mg for weeks 13-24; for group B it was 400 mg for weeks 13-36 (with placebo given for weeks 0-12). All ribavirin doses in group C were 400 mg, and peg-IFN alpha 2a doses in all three groups were 135 mcg, said Dr. Basu of Columbia University College of Physicians and Surgeons, New York.

Patients in the study included 26 men and 10 women with a mean age of 58 years, a mean body mass index of 26.6 kg/m2, and a mean viral load of 869,000 IU/mL who were treated between May 2011 and November 2012. All had end-stage renal disease and were on hemodialysis for a mean of 6 years. The groups were well balanced with respect to BMI, race, viral load, and disease genotype.

Adverse events that occurred more often in the telaprevir groups (A and/or B), compared with group C, included anemia, neutropenia less than 750 ANA, thrombocytopenia, skin rash, anorectal dysfunction, dysgeusia, depression, and constipation. Neuropathy was more common in group C.

Protease inhibitors are now part of the standard of care for treatment of chronic hepatitis C, genotype 1. Telaprevir was approved in May 2011 for this purpose.

Since the drug is primarily metabolized in the liver and excreted in the feces, thus limiting renal toxicity, it was considered a promising treatment option for the 3% of chronic hepatitis C patients with end-stage renal disease on hemodialysis – a population with progressive fibrosis and high mortality, Dr. Basu said.

The findings of this pilot study suggest that truncated triple therapy that includes telaprevir does indeed have an advantage over the standard of care for this special population, he concluded, noting that the telaprevir regimen requires further evaluation in a large prospective trial.

Dr. Basu disclosed financial relationships with Gilead Science, BMS, ROMAX, Genentech, Vertex, Otsuka, Takeda, Three Rivers, GI Pathology, and Salix.

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