Interferon alfa evaluation

Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, FisceUa M, Yu R, Osborn BE, Cronin PW, Ereimuth WW, McHutchison JG, Subramanian GM (2006) A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 44 671-678... 

Although depressive symptoms are usually ascribed to interferon alfa alone, ribavirin could also contribute to their occurrence. Among 162 patients with chronic hepatitis C treated with peginterferon alfa-2b (1.5 micrograms/ kg once weekly) plus weight-based or standard-dose ribavirin and prospectively evaluated for the incidence and... 

Of 33 patients with chronic hepatitis C treated with interferon alfa, 9 MU/week for 3-12 months, prospectively evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) before and after 12 weeks of treatment, eight developed depressive symptoms, of whom four had major depression without a previous psychiatric history (381). All four recovered after treatment with antidepressants. This study confirmed that a high baseline MADRS is significantly associated with the occurrence of depressive symptoms. 

Recombinant aldesleukin-binding antibodies were detected in the half of 205 patients with metastatic cancer but there were neutralizing antibodies in only 7% (113). No significant difference in incidence was found between subcutaneous and continuous intravenous administration. In another study, none of the patients receiving aldesleukin alone developed neutralizing antibodies, whereas 18% of patients treated with aldesleukin and interferon alfa-2b had antibodies (114). Whatsoever, the clinical relevance of recombinant aldesleukin-neutralizing antibodies has not been accurately evaluated and a loss of response was apparently documented in only one patient (115). 

In a study of 67 patients with chronic viral hepatitis, the self-administered Minnesota Multiphasic Personality Inventory (MMPI), which determines the patient s psychological profile, significantly correlated with the clinical evaluation and was a sensitive and reliable tool for identifying patients at risk of depressive symptoms before the start of interferon alfa therapy (112). It was also successfully used to monitor patients during treatment. 

Dubois J, Hershon L, Carmant L, Belanger S, Leclerc JM, David M. Toxicity profile of interferon alfa-2b in children a prospective evaluation. J Fediatr 1999 135(6) 782-5. 

In contrast to interferon alfa, the autoimmune consequences of interferon beta treatment have been poorly evaluated. Interferon beta does not appear to be associated with the appearance or increased titres of several auto-antibodies, and no clinical features of autoimmune disease were observed in patients receiving a 6-month course of interferon beta-la or interferon beta-lb (66,67). 

A single intramuscular dose of recombinant human interferon alfa-2a 18 million units was given to 8 healthy subjects alone, or after one day of either aspirin 650 mg every 4 hours, paracetamol 650 mg every 4 hours or prednisone 40 mg daily, for a total of 8 days. None of these additional drugs reduced the interferon adverse effects of fever, chills, headache, or myalgia. Only prednisone appeared to reduce one of the two measures of interferon activity. In a later similar study by the same research group, the effect of the same drugs and doses (started 3 days before the interferon) was evaluated with a lower dose of interferon alfa-2a (3 million units). When data for aspirin, paracetamol or prednisone was combined the... 

Alpha interferons, including peginterferon alfa-2b, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Closely monitor patients with periodic clinical and laboratory evaluations. Withdraw from therapy patients with persistently severe or worsening signs or symptoms of... 

Drug Interactions According to the product label, interactions between Intron A and other drugs have not been fully evaluated. Caution should be exercised when administering Intron A therapy in combination with other potentially myelo-suppressive agents such as zidovudine. Concomitant use of alfa interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels. 

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