Pegylated Interferon Alpha-2a Therapy Research Articles

Ten‐year follow‐up of a randomized controlled clinical trial in chronic hepatitis delta

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n=19), Group II (n=20), Group III (n=21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n=8) in PEG-IFNα-2a arms and 58% (n=11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.

FRI-326 - Establishment of persistent functional remission of HBV and HDV infection following REP 2139 and pegylated interferon alpha 2a therapy in patients with chronic HBV/HDV co-infection: 18 month follow-up results from the REP 301-LTF study

FRI-326 - Establishment of persistent functional remission of HBV and HDV infection following REP 2139 and pegylated interferon alpha 2a therapy in patients with chronic HBV/HDV co-infection: 18 month follow-up results from the REP 301-LTF study

Add-on Pegylated Interferon Alpha-2a Therapy in Chronic Hepatitis B Japanese Patients Treated with Entecavir.

Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels <100 IU/mL. Hepatitis B e antigen (HBe Ag) seroconversion rate was 25% (2/8), and VR rate was 52% (12/23). CR was observed in four patients (17%). However, CR rate in baseline HBs Ag level <2000 IU/mL and HBe Ag negative patients was 50% (4/8). Univariate analysis showed that the percentage of HBs Ag level reduction at week 12 was significantly associated with VR. The area under the curve value was 0.848. Adding PEG-IFN-α-2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.

Su1030 Half Dose Pegylated Interferon Alpha 2A Therapy is Effective in Achieving SVR in Hepatitis C: Genotype 2/3 Korean-American Patients With Normal BMI in a 9 Year Study

Su1030 Half Dose Pegylated Interferon Alpha 2A Therapy is Effective in Achieving SVR in Hepatitis C: Genotype 2/3 Korean-American Patients With Normal BMI in a 9 Year Study

Experience with pegylated interferon -2a in advanced myeloproliferative neoplasms in an international cohort of 118 patients

The Philadelphia negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial vascular and transformative complications. Standard therapy for high-risk disease, particularly in patients that have failed initial therapy, remains controversial. Non-pegylated interferon has previously been shown to be effective in controlling erythrocytosis, thrombocytosis and thrombotic complications, but was found to have poor tolerability and excessive adverse effects. Recently, pegylated interferon alpha-2a was introduced and found to be better tolerated and less toxic than standard interferon. In addition, in recent phase II trials, pegylated interferon alpha-2a therapy was found to induce both hematologic and molecular remissions. We retrospectively analyzed 118 myeloproliferative patients who underwent pegylated interferon alpha-2a treatment. Responses were evaluated by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were analyzed.

High Degree of Hematological Response After Pegylated Interferon Alpha-2a Therapy In Myeloproliferative Neoplasms

AbstractAbstract 5055 Objective:To retrospectively assess hematological response rates, and other clinical and molecular variables, in MPN patients treated with pegylated interferon α-2a (Pegasys®, Roche Ltd). Responses were graded according to criteria published by the European Leukemia Net for PV and ET (Barosi G et al Blood 2009;113:4829), with the exception that mesurement of spleen size using ultrasound was not routinely performed, and the European Myelofibrosis Network for PMF (Barosi G et al Blood 2005;106:2849), respectively. Patient characteristics:The 23 patient cohort consisted of 13 PV, 5 ET, 3 PMF and 2 post-ET/PV MF pts. Thirteen pts were JAK2V617F+, 6 were JAK2V617F wt, and in 4 pts JAK2 status is unknown. Median age was 50 years (range 26–69), 13 were female and 10 male. Median time from MPN diagnosis to start of pegylated interferon α-2a (Peg-IFN) therapy was 67 months (range 0–204). Six pts had a previous thrombotic event (TIA=2, portal vein thrombosis=2, DVT lower extremity=2), and 2 pts had a previous major hemorrhage (gynecological=1, gastrointestinal=1). Eleven pts had previously received therapy with anagrelide (n=8), hydroxyurea (n=4), interferon α-2b (n=1), busulfan (n=1) or P32 (n=1), while 12 pts had not received bone marrow suppressive therapy. All PV and ET pts were on aspirin. Phlebotomies were performed in PV with the aim of keeping the hematocrit < 0.45. Peg-IFN was given at a dose of 90 μg/week in 16 pts, 135μg/week in 6, and 180μg/week in 1. Results:The overall hematological response rate (CR+PR) was 18/21 (86 %), 14 pts achieving CR and 4 PR. Two pts are too early to evaluate at the time of astract submission. One PV and 1 PMF patient were non-responders. Resonse rates were similar in PV vs ET, female vs male pts, and previously treated vs previously untreated pts. Median time of follow-up on Peg-IFN therapy is 16 months (3+ - 49+). Thirteen pts are still on therapy, 9 in CR, 2 in PR, and 2 too early to evaluate. These 13 pts have very limited or no side effects. Therapy has also been stopped according to plan after long hematological CR with molecular response in 2 pts. Therapy has been discontinued in 8 pts, in five (22 %) due to side effects (depression n=3, joint pain n=3, hair loss n=2, pruritus n=1), non-response in 2 pts, and PMF progression in 1. Serial JAK2V617F measurements are available at time of abstract submission in 4 pts, 1 achieved molecular CR, 2 PR whereas 1 patient treated for 5 months had no molecular response. Three of 4 mildly anemic MF pts normalized their hemoglobin (HgB 113 → 137, 106 → 123, and 110 → 125 respectively). In one PMF patent a clear reduction of marrow fibrosis was noted, whereas it progressed in another. No thromboembolic or bleeding complications were observed during PEG-IFN therapy. Longer follow-up, as well as additional molecular and morphological studies will be presented. Conclusions:Pegylated interferon α-2a induced a higher hematological response rate with improved tolerability, compared to our previous experience with Peg-IFN α-2b (Samuelsson et al Cancer 2006;106:2397), although the current number of patients is limited. However, the two previous publications that describes Peg-IFN α-2a therapy in larger MPN patients cohorts have observed results similar to ours (Kiladjian JJ et al Blood. 2008;112:3065, Quintás-Cardama A et al J Clin Oncol. 2009;27:5418). Molecular responses noted in a subset of patients further highlights the effect of Peg-IFN α-2a on the malignant clone in MPN:s. Peg-IFN α-2a is a valuable therapeutic alternative in patients who tolerate initial side effects, and will soon be compared to hydroxyurea in a randomized trial in high-risk PV and ET pts performed by the MPD research consortium. Disclosures:Samuelsson:Roche Sweden: Advisory board on use of recombinant erytropoetin. Off Label Use: Alpha-interferon does not have a label for use in myeloproliferative neoplasms. Merup:Roche Sweden: Received honoraria for lectures on rituximab use in lymphoma.

Pegylated Interferon Alpha-2a Therapy for Patients with High Risk Essential Thrombocytemia: a Retrospective Analysis on 59 Patients.On Behalf of the French Intergroup of Myeloproliferative Disorders (FIM)

AbstractAbstract 1974 Background:Conventional therapeutic guidelines in essential thrombocytemia (ET) are based on established criteria of higher incidence of vascular complications: age more than 60 years, history of thrombosis, platelets more than 1000–1500 ×109/L and cardio-vascular risk factors. Hydroxyurea or anagrelide are the most commonly used cytoreductive therapy for high risk ET. Despite a proven activity of Interferon-alpha (IFN-α) in Ph negative myeloproliferative disorders, generalized use and efficacy have been hampered by frequent side effects. Nonetheless it is still a nonleukemogenic therapeutic option for younger patients and during pregnancy. More recently, phase II trials using Pegylated (Peg-) forms of IFN-α in patients with polycythemia vera (PV) or high risk ET have provided interesting results: first the superior toxicity profile is generally associated with a rapid hematologic response Second the molecular response described for a subset of JAK2 V617F positive PV or ET patients treated with Peg-IFN α-2a have indicated a selective targeting of the malignant clone with that latter agent. Methods:We revised cases of high risk ET having being or currently treated with IFN-α and reported by centres of the French Intergroup of myeloproliferative disorders (FIM). The current retrospective analysis was performed on data collected for the first 67 patients (pts) that have been observed for a median of 72 months (range 11–273). Among them, 59 pts have received Peg-IFNα-2a therapy. Assessment of the hematologic responses was performed at months 1, 2, 3 and then every 6 months. Results:For the entire cohort, median age was 37 years (range 17–64) and sex ratio F/M of 2.33. Previous thrombosis was observed in 19 cases and micro vascular disturbance in 4 pts. At diagnosis, median platelets count was 926.0×109/L (range 428.0; 4000.0), haemoglobin 14g/dl (8.0-14.1), leucocytes count 9.7×109/L (2.7-28.0). Detection of the Jak2V617F mutation was positive in 33 cases and negative for 26 pts.Median time from diagnosis to IFN-α was 50 months (1-256 months). IFN-α was generally administered as second line after Hydroxyurea. No prior therapy has been used for 6 pts. Reasons for IFN-α initiation were absence of hematologic response (31%), toxicity to the prior treatment (14%), pregnancy (16%), or medical decision for younger pts (39%).Of 67 pts of the cohort, 59 pts have been treated with Peg-IFNα-2a with a median duration of Peg-IFNα-2a of 16 months (range 1 day to 45 months). Efficacy and safety of the Peg-IFNα-2a were assessed in that subgroup. Thus 58 pts were evaluable for the hematologic response with at least 1 month exposure to Peg-IFNα2a.Overall, absence of response was observed in 4/58 (7%) pts, partial hematologic responses in 9/58 (16%) and complete hematologic response (CHR) was achieved for 45/58 (76%) of patients according to the European LeukemiaNet criteria. Cumulative incidence of CHR at 1, 3, and 6 months was 29%, 52% and 65% respectively. At 18 months, estimated probability of CHR was 83% (95%CI 71–92). At the last follow up 47/58 (81%) of the pts were still treated with Peg-IFNα-2a and overall 36 pts are in CHR. Median time to achieve CHR was 3 months. Median dose of Peg-IFNα-2a was 88μg weekly (range 28–180μg weekly). Reasons for discontinuation of Peg-IFNα2a (11pts) were related non hematologic toxicity in 7/59 pts (12%), 1 failure, and 3 pregnancies.By analysing the response according to the Jak2 status (58 pts), the overall CHR rates were 31 and 14 for the 37 JAK2 V617F mutated and the 21 JAK2 negative pts respectively. The median time to achieve CHR was 6 and 3 months. At 18 months the estimated CHR rates were 87% (73-95) and 66% (45-86). The difference is not statistically significant. Median doses of Peg-IFNα2a were 90μg (12-180) and 75μg (45-144) weekly. Duration of exposure to Peg-IFNα2a was 16 months (1-36) and 15 months (1-45). Conclusion:This retrospective analysis is the first attempt to present results on efficacy and tolerance of Peg-IFN on a large cohort of high risk ET not included in clinical trials. These results support the use of Peg-IFN in HR ET pts. Increase patients number, molecular analysis and update of these preliminary data will be presented. Disclosures:Off Label Use: Interferon alpha and Pegylated-Interferon alpha for myeloproliferative disorders.

Pegylated interferon alpha-2a for treatment of chronic HCV infection in hemodialysis patients: a single Saudi center experience

Chronic hepatitis C infection is common among patients on dialysis. While the associated liver disease is usually relatively mild during dialysis, disease progression can accelerate due to immunosuppression following kidney transplantation, and interferon therapy after transplantation stimulates graft rejection. Pegylated interferon and ribavirin are now the recommended treatment for chronic hepatitis C virus in patients without renal failure. However, until now, there has been relatively little information on the efficacy and tolerability of pegylated interferon in dialysis patients. To evaluate the response to pegylated interferon alpha-2a in chronic hepatitis C-infected patients on chronic hemodialysis. This controlled study included 28 patients with end-stage renal disease who had been on dialysis in the Prince Salman Center for Kidney Disease for more than 6 months and tested positive for HCV RNA on repeated occasions. Thirteen patients were treated with pegylated interferon alpha-2a therapy (of which three were also receiving ribavirin), and the remaining fifteen served as controls. Viral genotyping and both qualitative and quantitative PCR were carried out before starting therapy. Treatment was continued for 48 weeks. After 24 weeks of treatment, the biochemical and virological responses were evaluated. Biochemical response was evaluated at the end of the treatment, with sustained virological response (SVR) being evaluated 24 weeks later. The side effects were monitored throughout the treatment period. All patients in the treatment group completed 48 weeks of therapy without any drop out. Their mean age was 43.38 ± 11.62 years. After 24 weeks of therapy, 10 patients (76%) were initial responders, while 3 patients (24%) were resistant. Six months after termination of therapy, 9 patients (69%) were sustained responders, while one patient relapsed. Their ALT and AST dropped from 55.78 ± 33.79 IU/dl and 34.04 ± 19.58 IU/dl before starting therapy to 27.22 ± 16.54 IU/dl and 18.88 ± 12.28 IU/dl after termination (P = .06 and .08, respectively). Their mean hemoglobin (Hb) level dropped from 11.05 ± 1.43 to 9.48 ± 1.24 g/dl (P = 0.3), and white blood cell count (WBC) dropped from 6.82 ± 2.6 × 10(3)/mm(3) to 4.1 ± 2.34 × 10(3)/mm(3); (P = 0.57). Platelet count fell from 194.56 ± 129.78 × 10(3)/mm(3) to (152.33 ± 107.66 × 10(3)/mm(3); P = 0.39). When initial responders (n = 10) were compared to resistant patients (n = 3), the only observable difference was higher ALT and AST levels in resistant patients. Pegylated interferon alpha-2a was well tolerated, and none of the patients stopped interferon because of hematological side effects while dose modification was carried out in most of the patients. All three patients who received combination therapy from the start were sustained responders. None of the patients in the control group seroconverted to HCV negative status during the study period. Pegylated interferon alpha-2a was well tolerated among our hemodialysis patients. Hematological disturbances appeared to be the most important adverse effects. At the end of therapy a response rate of up to 76%, with 69% sustained response, can be obtained with pegylated interferon alpha-2a therapy.

Efficacy and safety of pegylated interferon alpha-2a therapy for chronic hepatitis C in HIV-infected patients with haemophilia

The objective of this study was to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) alpha-2a monotherapy in a cohort of Chinese haemophilic patients co-infected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and undergoing highly active antiretroviral drugs therapy. Twenty-two (n = 22) patients with CD4 lymphocyte counts over 200 cells microL(-1) were treated with 180 microg of PEG-IFN alpha-2a subcutaneously once in a week for 48 weeks. HCV load (HCV RNA), HIV load (HIV RNA) and CD4 lymphocyte counts were measured at baseline and 4, 12, 24, 48 and 72 weeks after initiation of anti-HCV therapy. Efficacy and safety were analysed according to baseline CD4 status (> or =350 cells microL(-1)). Significant HCV-RNA decreases (>1 log(10) copies mL(-1)) were observed through week 72 after PEG-INF alpha-2a monotherapy across both CD4 strata. CD4 status was not associated with treatment outcomes as evaluated using rapid viral response rate (P = 0.655), early viral response rate (P = 0.387), end-of-treatment viral response rate (P = 1.000) or sustained viral response rate (SVR, P = 0.674). A sustained virological response was achieved in nine patients (41%), five with genotype 2a (83%) and four with genotype 1b (25%, P = 0.023). SVR was HCV genotype dependent. Eleven patients required a dose reduction in PEG-IFN alpha-2a. PEG-IFN alpha-2a monotherapy could be considered as a safe and effective option for the treatment of HCV infection in HIV patients with haemophilia, particularly in resource-limited settings. While higher CD4 lymphocyte counts resulted in greater HCV-RNA reduction, HCV genotype was a predictor for sustained virological response.

Antiphospholipid syndrome during pegylated interferon alpha-2a therapy for chronic hepatitis C

A great variety of autoimmune side effects have been reported during interferon alpha therapy. The presence of anticardiolipin antibodies during interferon alpha therapy in chronic hepatitis C has also been reported. There are no reports on the occurrence of antiphospholipid syndrome in patients with chronic hepatitis C while on pegylated interferon alpha therapy. We report a case of a 46-year-old man who developed antiphospholipid syndrome 12 weeks after starting pegylated interferon alpha plus ribavirin for chronic hepatitis C. The clinical presentation of antiphospholipid syndrome was primary adrenal insufficiency secondary to bilateral adrenal haematoma and subclavian vein thrombosis. A pathogenic role of pegylated interferon alpha as a trigger factor for antiphospholipid syndrome development is suggested.