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Ribavirin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Emily Woolnough, Amanda Wade, Joe Sasadeusz
Treatment of HCV infection was further improved and simplified with the introduction of pegylated interferon (interferon modified chemically by pegylation; see Chapter 260, Interferon alpha), a longer-acting form of interferon with a half-life enabling weekly rather than three times weekly dosing. Three large randomized, double-blind, controlled trials in treatment-naive patients showed that combination treatment with peginterferon and ribavirin resulted in higher rates of SVR than treatment with standard interferon and ribavirin; an example of the outcomes of treatment of HCV infection with peginterferon and ribavirin is shown in Figure 259.6, and the results are summarized in Table 259.7. One trial of 1530 patients assessed treatment with peginterferon alpha 2b 1.5 μg/kg weekly in combination with ribavirin 800 mg daily. Among genotype 1–infected patients treated with peginterferon alpha 2b and ribavirin, the SVR rate was 42%, compared with 33% in the standard interferon and ribavirin arm. Among patients infected with a genotype other than 1a or 1b, about 80% an SVR achieved regardless of the type of interferon given (Manns et al., 2001). A large trial of 1311 patients investigated the effect of duration and dose of ribavirin when used with peginterferon alpha 2a, 180 μg weekly, and established that SVR rate improved to 52% in genotype 1–infected patients with weight-based ribavirin dosing (weight < 75 kg, 1000 mg daily; weight > 75 kg, 1200 mg daily) and 48 weeks of treatment. In comparison, patients infected with genotypes 2 or 3 had similar rates of SVR (80%) regardless of the duration of therapy (24 or 48 weeks) or use of a lower ribavirin dose, 800 mg/day (Hadziyannis et al., 2004). Based on data from these key studies, the American Association for the Study of Liver Diseases (AASLD) recommends specific doses and treatment durations of ribavirin when used in combination with peginterferon alpha 2a (see Table 259.8).
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In clinical practice, recombinant IFN-α formulations exist in 3 isoforms (alfa-2a, alfa-2b, and alfa-2c). Peginterferon alfa-2a (marketed under the name Pegasys™) is approved as adjuvant treatment for patients with completely resected Stage 3 or Stage 4 high-risk melanoma, as first-line treatment for patients with mRCC (alfa-2a, and alfa-2b in combination with bevacizumab), AIDS-related Kaposi’s sarcoma (alfa-2b), follicular lymphoma (alfa-2b), HCL (alfa-2a, alfa-2b), chronic myelogenous leukemia (Philadelphia chromosome-positive alfa-2a), condyloma acuminata (alfa-2b), and cervical intraperitoneal neoplasms (alfa-2b). Peginterferon alfa-2b (marketed as ViraferonPeg™) is approved for the treatment of hepatitis C. Two non-pegylated preparations (IntronA™, Roferon-A™) are also approved for administration by subcutaneous or intramuscular injection. The polyethylene glycol-conjugated (i.e., “pegylated”) derivatives of interferon alfa have enhanced persistence in the bloodstream due to their peg coating, although these products are mainly used in the treatment of chronic hepatitis B and C, often in combination with ribavirin. In some countries, interferon alfa-2a (rbe) is also used in a topical eye formulation for the treatment of ocular surface squamous neoplasia (OSSN), a cancer of the eye. IntronA™, which contains interferon alfa-2b (rbe), is approved for use in hairy cell leukemia and chronic myelogenous leukemia (CML) either as monotherapy or in combination with cytarabine, and is also used to treat lymph or liver metastases of carcinoid tumors, follicular lymphoma, maintenance of remission in multiple myeloma, and as an adjunct to surgery in malignant melanoma. It is also approved for use in chronic hepatitis C. Roferon-A™, which contains interferon alfa-2a (rbe), is used to treat AIDS-related Kaposi’s sarcoma, recurrent or metastatic renal cell carcinoma, hairy cell leukemia, chronic myelogenous leukemia (CML), progressive cutaneous T-cell lymphoma, and follicular non-Hodgkin’s lymphoma. It is also used as an adjunct to surgery in malignant melanoma and to treat chronic hepatitis B and C.
Potential value and impact of data mining and machine learning in clinical diagnostics
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Maryam Saberi-Karimian, Zahra Khorasanchi, Hamideh Ghazizadeh, Maryam Tayefi, Sara Saffar, Gordon A. Ferns, Majid Ghayour-Mobarhan
Three studies have applied DT models to predict therapeutic response in patients with viral disorders. Kurasoki et al. applied DT analysis for the pretreatment prediction of response to pegylated interferon-ribavirin therapy for chronic HCV and found five relevant features, which were steatosis, LDL‐C, age, blood sugar, and GGT [67]. Thus, a DT model may be useful for the prediction of response to pegylated interferon-ribavirin therapy. Using regression and DT analyses, Khairy et al. conducted a study to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in Egyptian patients with chronic HCV [68]. The findings suggest baseline AFP is an important predictor of antiviral therapy response in chronic HCV. In addition, absence of the C allele (TT genotype) was significantly associated with lack of response to the therapy. El Raziky et al. used data mining to identify the predictors of virological response in chronic HCV patients treated with peginterferon alpha-2a or with peginterferon alpha-2b [69]. For both treatment types, results showed that male gender, a low thyroid stimulating hormone (TSH), and decreased hemoglobin were predictors of favorable response, while serum viral load of >600 × 103 IU/mL and AFP >10 ng/mL were related to failure of response.
Five patients who died during treatment for adult Still’s disease
Published in Modern Rheumatology, 2018
Rena Motohashi, Kazuhiko Uchiyama, Hidekazu Ikeuchi, Yoshihisa Nojima, Keiju Hiromura
Here, we provide a specific description of patient 3, an interesting and informative case. The patient, a 46-year-old male, received a diagnosis of ASD owing to high fever, skin rash, lymphadenopathy, hepatosplenomegaly, neutrophilia, negativity for rheumatoid factor and anti-nuclear antibody, markedly-elevated ferritin (52,932 ng/ml), and ruling out of other febrile diseases. He successfully achieved remission under steroid monotherapy, which was withdrawn within 3 months. Thereafter, ASD remained inactive over an 8-year steroid-free period. However, high fever recurred 4 months after the administration of peginterferon alfa-2b and ribavirin to treat hepatitis C infection. A constellation of signs and symptoms, including elevated ferritin (32,600 ng/ml), confirmed the diagnosis of relapsed ASD. The patient partially responded to steroid therapy, but the disease flared up while tapering steroid dosage and HPS developed with severe pancytopenia. Methylprednisolone pulse therapy was repeated five times over the following 6 months, and cyclosporine or tacrolimus were added. However, ASD was uncontrollable and the patient eventually died of respiratory failure, presumably because of pneumonia. We suggest that the treatment for HCV with interferon alpha and ribavirin contributed to the flare-up of ASD that had been inactive for a relatively long period of time.
Childhood-onset craniopharyngioma: latest insights into pathology, diagnostics, treatment, and follow-up
Published in Expert Review of Neurotherapeutics, 2018
Agnieszka Bogusz, Hermann L. Müller
Based on preliminary promising results of systemic peginterferon alpha-2b treatment by regular subcutaneous injections in CP with cystic tumor compartments, a randomized multicenter trial was initiated. However, due to a lack of efficacy, the study was terminated recently after interim analyses (NCT: 01964300). Accordingly, it has to be pointed out that intracavitary sclerosing effects of interferon alpha are limited to cystic tumor portions without proven effects on solid tumor components and there are no available data published on prospective long-term follow-up after this treatment.