PEG IFN/RBV in Relapsers & Nonresponders

Combination IFN/RBV Viral load nonresponders do not respond when treated again, but preliminary data shown at DDW suggests they may respond to pegylated interferon plus RBV.

At the Schering symposium Sunday nite, Ira Jacobson, MD reported preliminary data suggesting that some IFN/RBV combination nonresponders may respond to Pegylated IFN+RBV with undetectable viral load (<100). He cautioned that the relapse rate may be larger than expected since the patients are nonresponders so don’t place too much emphasis on this preliminary data. He mentioned that Schering is studying a high dose of PegIntron of 3.0 ug/kg. He suggested that 18 months therapy or more may be more effective for certain hard to treat populations including genotype 1, advanced fibrosis, and late responders (PCR+ at 3 months) (See Benelux study at EASL 2001 in NATAP web site EASL Reports). The groups of patients are being studied (n=330): IFN monotherapy nonresponders, combination IFN/RBV relapsers, and combination nonresponders. Patients were randomized to 1 of 2 regimens: PEG INTRON a-2b 1.0 ug/kg (low dose) once weekly + RBV 1000-1200 mg/day, or PEFG INTRON a-2b 1.5 ug/kg once weekly (high dose) +RBV 800 mg/day. Treatment is for 48 weeks with 24 weeks follow-up.

So far, 123 patients have reached 24 weeks, and there have been (perhaps 10%-15%) so this is not an intent-to-treat analysis. Of the patients that have reached 24 weeks:

HCV PCR Negative IFN nonresponders 8/15 (53%) IFN/RBV relapsers 18/18 (100%) IFN/RBV nonresponders 22/90 (24%) Genotype 1 18/81 (22%) Genotype non 4/9 (44%)

Preliminary Results Broken Down By Treatment arm:

PEG-IFN a-2b 1.0 mg/kg 1.5 ug/kg RBV: 1000-12—mg/day 800 mg/day Genotype 1 8/48 (17%) 10/33 (30%) Genotype non-1 2/4 (50%) 2/5 (40%)

In a few other studies being reported here at DDW, Jacobson reported similar findings: 254 patients enrolled in Gaglio study receiving 1.5 ug/kg PegIntron+800 RBV; 13/73 (18%) on nonresponders were PCR negative at week 24. Jacobson cautioned that these nonresponders may include IFN monotherapy & combination nonresponders.

In Dalke study 102 patients completed 24 weeks. Of the 62 IFN/RBV nonresponders;

PegIntron 0.5 ug/kg (low dose) +RBV 800 mg/day: 1/34(3%) PCR negative PegIntron 1.5 ug/kg + RBV 800 mg/d: 9/28 (32%) PCR neg.

Of the 40 relapsers:

PegIntron 0.5 ug/kg + 800 mg RBV/d: 11/21 (52%) PCR neg. PegIntron 1.5 ug/kg + 800 RBV mg/d: 13/19 (68%) PCR neg.