Idrian García-García

Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

BackgroundTuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments.MethodsTo evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 106 IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly.ResultsSputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed.ConclusionsThese data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged.

Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

BackgroundHigh antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC).MethodsA randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment.ResultsEighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms predominated in the IFN gamma group. No severe events were recorded.ConclusionThese data suggest that IFN gamma is useful and well tolerated as adjuvant therapy in patients with pulmonary atypical Mycobacteriosis, predominantly MAC. Further wider clinical trials are encouraged.Trial registrationCurrent Controlled Trials ISRCTN70900209.

Bioequivalence of Two Recombinant Interferon α-2b Liquid Formulations in Healthy Male Volunteers

AbstractObjective: Interferon (IFN) α-2b is a protein with antiviral, antiproliferative and immunoregulatory properties that is approved for several clinical indications. A new liquid, albumin-free, IFNα-2b formulation has recently been developed. This study aimed to evaluate the equivalence of the pharmacokinetic, pharmacodynamic and safety properties of the new formulation with a reference one in healthy male volunteers. Methods: A randomised, crossover, double-blind study with a 3-week washout period was performed in which Heberon Alfa R®? (formulation A) and Viraferon® (formulation B) were compared. A single 20 × 106 IU IFNα-2b dose was administered subcutaneously to 14 apparently healthy male subjects. Serum IFN level was measured over 48 hours by enzyme immunoassay (EIA) and by antiviral activity titration. Clinical and laboratory variables were determined, as were pharmacodynamic and safety criteria. Results: Groups were homogeneous with regard to all demographic and baseline variables. Pharmacokinetic comparison by EIA did not show differences between the formulations: area under the curve (AUC) 2572 versus 2561 ng •h/L, maximum plasma concentration (Cmax) 318 versus 354 ng/L, time to Cmax (tmax) 8.2 versus 8.5h, elimination half-life (t1/2) 5.87 versus 6.08h, terminal elimination rate (λ) 0.122 versus 0.118h−1, and mean residence time (MRT) 10.9 versus 12.0h for formulations A and B, respectively. The differences never reached 20%, which is the clinically significant threshold. The 90% confidence interval of the ratio between them was in all cases within the 0.8, 1.25 range. The two formulations were clinically equivalent with regard to serum IFN antiviral activity titration (0.8, 1.25 criterion) regarding their pharmacokinetic parameters. There were no significant differences with respect to the pharmacodynamic variables: serum gB2-microglobulin and temperature increase. Heart rate and blood pressure changes did not differ either. Both products provoked similar haematological count decreases and had similar safety profiles. The most frequent adverse reactions were fever, tachycardia, headache and arthralgias. Conclusion: The overall analysis strongly suggests the bioequivalence of these two products.

Adjuvant Interferon Gamma in the Management of Multidrug - Resistant Tuberculosis

Tuberculosis is an opportunistic infection, the minute it finds an immunocompromised host, it flourishes. The risk of tuberculosis is much higher in patients who are human immunodeficiency virus (HIV) positive. Drug resistance among microbes is testimony to their adaptive skills. In Mycobacterium Tuberculosis the resistance occurs due to random, single step, spontaneous mutation and is invariably induced by inadequate or incomplete therapy. This resistance was termed as Multidrug Resistant (MDR) tuberculosis when the organism was resistant to more than one anti-tuberculosis drug. The presence of MDR tuberculosis, in general population, exposes the immunodeficient patients to an MDR strain of tuberculosis, which has very serious consequences for them. The risk of tuberculosis is also higher in non-HIV immunocompromised patients such as those with genetic absence of Interferon (IFN) gamma receptors, or acquired immune defect in the elderly. In either these situations IFN gamma or its absence seems to play a major role. In addition to the pulmonary infection, immunocompromised patients (with or without HIV) fall victim to extrapulmonary tuberculosis.