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BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) cessation can lead to hepatitis B surface antigen (HBsAg) clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96. METHODS: In this multicenter randomized-controlled clinical trial, 180 non-cirrhotic patients with HBeAg-negative chronic hepatitis B on continuous NUC therapy for ≥2.5 years, with HBV DNA levels <60 IU/ml, were randomized to discontinue NUC therapy (n = 90) or receive 48 weeks of PegIFN-α-2a treatment (n = 90). Patients were followed up for up to 96 weeks. The primary endpoint was the virological relapse rate up to week 96. RESULTS: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, p <0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, p = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, p = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group. CONCLUSIONS: Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and leads to higher HBsAg loss rates than NUC treatment cessation alone in patients with HBeAg-negative chronic hepatitis B. IMPACT AND IMPLICATIONS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimized scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized-controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96 in patients with HBeAg-negative chronic hepatitis B. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, p <0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group up to week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER: NCT02594293.
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Severe combined immunodeficiency (SCID) is one of the most serious inborn errors of immunity leading to a fatal infection in early infancy. Allogeneic hematopoietic cell transplantation (HCT) or elective gene therapy prior to infection or live-attenuated vaccination is the current standard of curative treatment. Even in the era of newborn screening for SCID, pretransplant control of severe infection is challenging for SCID. Multiple pathogens are often isolated from immunocompromised patients, and limited information is available regarding antiviral strategies to facilitate curative HCT. We herein present a case of successfully controlled pretransplant pneumonia after ribavirin and interferon-α therapy in an infant with RAG1-deficiency. A four-month-old infant presented with severe interstitial pneumonia due to a co-infection of rhinovirus and Pneumocystis jirovecii. The tentative diagnosis of SCID prompted to start antibiotics and trimethoprim-sulfamethoxazole on ventilatory support. Because of the progressive respiratory failure four days after treatment, ribavirin and then pegylated interferon-α were started. He showed a drastic response to the treatment that led to a curative HCT 32 days after admission. This patient received the genetic diagnosis of RAG1-deficiency. Currently, he is an active 3-year-old boy with normal growth and development. The review of literature indicated that rhinovirus had a comparable or rather greater impact on the mortality of pediatric patients than respiratory syncytial virus. Considered the turn-around time to the genetic diagnosis of SCID, prompt ribavirin plus interferon-α therapy may help to control severe rhinovirus pneumonia and led to the early curative HCT for the affected infants.
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Infecciones por Enterovirus , Enfermedades Pulmonares Intersticiales , Neumonía , Virus Sincitial Respiratorio Humano , Masculino , Lactante , Recién Nacido , Humanos , Niño , Preescolar , Rhinovirus , Ribavirina/uso terapéutico , Interferón-alfa/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Proteínas de Homeodominio/genéticaRESUMEN
BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced. RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus-infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection. CONCLUSIONS: Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments.
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Infecciones por Caliciviridae , Inmunodeficiencia Variable Común , Norovirus , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Infecciones por Caliciviridae/tratamiento farmacológico , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/tratamiento farmacológico , Inmunoglobulinas , Interferón-alfa/uso terapéutico , Norovirus/genética , Ribavirina/uso terapéutico , Ribavirina/farmacología , ARN Viral/genética , Replicación ViralRESUMEN
BACKGROUND: We aimed to evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat coronavirus disease 2019 (COVID-19) patients with prolonged postsymptomatic viral shedding. METHODS: We conducted a prospective, randomized controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged polymerase chain reaction (PCR) positivity. Patients were randomly assigned to receive either leflunomide (50 mg every 12 hours, 3 consecutive times, orally; then 20 mg once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN-α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN-α-2a alone for 10 days. The primary endpoint was the duration of viral shedding. RESULTS: A total of 50 COVID-19 patients with prolonged PCR positivity were randomized into 2 groups: 26 were assigned to the leflunomide plus IFN-α-2a group, and 24 were assigned to the interferon-alone group. Treatment with leflunomide was not associated with a difference from the interferon-alone group in the duration of viral shedding (hazard ratio for negative reverse-transcription PCR, 0.70 [95% confidence interval, .391-1.256]; Pâ =â .186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median durations of 29.0 (interquartile range [IQR], 19.3-47.3) days and 33.0 (IQR, 29.3-42.8) days, respectively (Pâ =â .170). Two leflunomide recipients were unable to complete the full 10-day course of administration due to adverse events. CONCLUSIONS: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN-α-2a beyond IFN-α-2a alone.
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COVID-19 , Adulto , Antivirales/farmacología , Antivirales/uso terapéutico , Dihidroorotato Deshidrogenasa , Humanos , Leflunamida/farmacología , Estudios Prospectivos , SARS-CoV-2 , Resultado del Tratamiento , Esparcimiento de VirusRESUMEN
BACKGROUND AND OBJECTIVE: Corneal neovascularization (CNV) is a vision-threatening condition arising from various corneal diseases. The aim of this study is to compare the effectiveness of bevacizumab and interferon alpha-2a (IFNα-2a) treatment on corneal neovascularization. MATERIALS AND METHODS: Twenty-four Wistar albino rats were used in this study. After cauterization of the cornea with a silver nitrate applicator stick, the control group received 0.1 mL saline solution, the second group received 0.1 mL IFNα-2a (IFNα-2a, 6 million international units [MIU]/0.5 mL), and the third group received 2.5 mg bevacizumab by subconjunctival injection. An additional injection was administered to each group on the fourth day. After one week, the corneal neovascularization rate and the longest neovascular sprout length were determined. RESULTS: The neovascularization rate (saline 0.65 ± 0.05; IFNα-2a 0.62 ± 0.07; bevacizumab 0.42 ± 0.11) with bevacizumab was significantly lower, more than those with IFNα-2a and saline (p < 0.001 and p < 0.001). The longest neovascular sprout length (saline, 4.00 ± 0.6 mm; IFNα-2a, 3.63 ± 0.52 mm; bevacizumab, 2.81 ± 0.65 mm) with bevacizumab was significantly shorter than those with saline and IFNα-2a (p = 0.001 and p = 0.012). CONCLUSIONS: Subconjunctival IFNα-2a has limited efficacy in the treatment of corneal neovascularization.
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Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Neovascularización de la Córnea/tratamiento farmacológico , Interferón alfa-2/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Animales , Bevacizumab/farmacología , Conjuntiva , Neovascularización de la Córnea/inducido químicamente , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Inyecciones Intraoculares/métodos , Interferón alfa-2/farmacología , Nitratos , Compuestos de Potasio , Ratas , Ratas Wistar , Nitrato de Plata , Factores de TiempoRESUMEN
INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model. MATERIAL AND METHODS: EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis. RESULTS: Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals. CONCLUSIONS: These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.
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OBJECTIVE: To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. METHODS: A total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 µg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment. RESULTS: The median treatment time for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). CONCLUSION: Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.
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Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , ADN Viral/sangre , Esquema de Medicación , Femenino , Humanos , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Adulto JovenRESUMEN
Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut-offs determined by maximized Youden's index for identifying patients likely to respond to therapy were as follows: 3.141 log10 IU/mL and 3.450 log10 U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log10 IU/mL and qHBcrAg 3.450 log10 U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based 'precision therapy'. Our results emphasize that the combination of PegIFN alpha-2a plus TDF with 53% of SR might be an alternative to finite therapy.
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Antivirales/uso terapéutico , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Medicina de Precisión/métodos , Adulto , Femenino , Hepatitis B Crónica/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Respuesta Virológica Sostenida , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
HBeAg negative chronic hepatitis B (CHB) is a frequent, progressive and difficult-to-cure phase of CHB. The end-point of therapy is to persistently suppress viral replication to halt progression of liver disease. Two different treatment strategies are currently available: a short-term course of pegylated interferon alpha (PEG-IFN) or long-term therapy with nucleot(s)ide analogues (NA), i.e. entecavir or tenofovir. Young patients with mild-to-moderate stages of liver disease can benefit from a 48-week course of PEG-IFN, while NA may be preferred in patients with more severe liver disease, in older patients, and in those who do not respond, are unwilling or have contraindications to PEG-IFN. Nucleot(s)ide analogues provide persistent viral suppression and biochemical normalization in almost all patients, together with the regression of fibrosis and the prevention of decompensation, but the effect on hepatocellular carcinoma rates is limited. Thus, NAs have become the most popular treatment strategy worldwide but lifelong administration is associated with high cost, unknown safety and adherence issues and an unknown risk of drug-resistance over time as well as limited rates of HBsAg seroclearance. On the other hand, PEG-IFN treatment may achieve a SVR in nearly a quarter of patients ultimately leading to HBsAg loss in almost 30-50%. Interestingly, response rates to PEG-IFN may further increase with more careful patient selection based on age, ALT and HBV DNA levels at baseline and by applying early on-treatment stopping rules based on HBV DNA and HBsAg kinetics. The combination of NA and PEG-IFN is not currently recommended but numerous studies are ongoing.
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Adenina/análogos & derivados , Antivirales/uso terapéutico , Quimioterapia Combinada/métodos , Guanina/análogos & derivados , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Organofosfonatos/uso terapéutico , Polietilenglicoles/uso terapéutico , Replicación Viral/efectos de los fármacos , Adenina/uso terapéutico , Guanina/uso terapéutico , Hepatitis B Crónica/sangre , Humanos , Cuidados a Largo Plazo/métodos , Proteínas Recombinantes/uso terapéutico , Tenofovir , Resultado del TratamientoRESUMEN
OBJECTIVES: The objective of this study was to determine the incidence of retinopathy in chronic hepatitis C patients treated with Pegylated interferon alpha 2a and Ribavirin. METHODS: This descriptive case series study was conducted in Medical Unit II of the Jinnah Hospital Lahore from September 2012 to February 2013. One hundred chronic hepatitis C patients visiting Medical Unit II outpatient department fulfilling inclusion criteria were selected for this study via non probability purposive sampling. Patients were started on pegylated interferon and ribavirin combination therapy. Subjects were subjected to dilated eye fundoscopic examination at the start of therapy and then after three months of the therapy. RESULTS: One hundred patients were included in this study. Out of these 100 patients 5% developed retinopathy whereas fundus examination was normal in rest of the patients. CONCLUSION: Interferon therapy can lead to retinopathy. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.
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AIM: We performed a clinical study to investigate potential association between serum levels of soluble adhesion molecules and virological response to pegylated interferon-alpha-2a (PEG IFN-α-2a) treatment in patients with chronic hepatitis B (CHB). METHODS: Thirty-two patients with chronic hepatitis B virus genotype B were recruited in this study, who were treated with PEG IFN-α-2a 180 µg every week and then followed up for 24 weeks. Thirty healthy control subjects were recruited from volunteer blood donors. Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble L-selectin (sL-selectin) in patients were investigated by enzyme-linked immunoassay before and after treatment. RESULTS: Serum concentrations of sICAM-1, sVCAM-1, sE-selectin and sL-selectin in CHB patients were significantly higher compared to the control group before treatment (P < 0.00001, respectively). In CHB patients responding to the PEG IFN-α-2a treatment, serum levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin were higher than those in non-responders before treatment (PI = 0.001, PV = 0.002, PE = 0.02, PL = 0.004). The levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin decreased in virological responders of treatment at 12 and 24 weeks (PI = 0.0001, PV = 0.00004, PE = 0.002, PL = 0.0004; PI = 0.00007, PV = 0.00001, PE = 0.0003, PL = 0.00003), while no obvious changes were observed in non-responders (P > 0.05, respectively). CONCLUSION: Results obtained indicated increased levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin could be related to virological response to PEG IFN-α-2a treatment in CHB patients, and have a prognostic effect on virological response.
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AIM: ME3738, a derivative of soyasapogenol B, enhances the anti-hepatitis C virus (HCV) effect of interferon in an in vitro replication system and an in vivo mouse model of HCV infection. ME3738 plus pegylated interferon (PEG IFN)-α-2a treatment for 12 weeks decreased HCV RNA levels in enrolled late virus responder (LVR) patients with relapsed HCV. Half of the patients reached undetectable HCV RNA level. The present clinical study of ME3738 was conducted in naïve chronic hepatitis C patients to investigate the sustained virological response (SVR) and safety of 48-week treatment with ME3738 plus PEG IFN-α-2a. METHODS: Subjects (n = 135) with genotype 1b chronic hepatitis C with high viral loads were divided into three groups (ME3738 50 mg b.i.d., 200 mg b.i.d. or 800 mg b.i.d.). ME3738 was administrated p.o. and PEG IFN-α-2a (180 µg/week) s.c. for 48 weeks, and SVR was assessed at 24 weeks of treatment-free follow up. RESULTS: The viral disappearance rates at 12 and 48 weeks were 23.0% and 48.9%, respectively. SVR was seen in 5.9% of subjects. ME3738 did not worsen the adverse reactions generally seen with PEG IFN-α-2a treatment, and any adverse reactions specific to ME3738 were not observed. CONCLUSION: ME3738 plus PEG IFN-α-2a treatment to naïve chronic hepatitis C patients showed an antiviral effect and a good safety profile up to 48 weeks. However, HCV RNA was again detected in many subjects after treatment termination. Even though ME3738 is not enough to suppress HCV reproduction in this treatment. ME3738 was concurrently used with PEG IFN-α-2a treatment; however, a clear additional effect on SVR was not confirmed.
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PURPOSE: To report the efficacy of pegylated interferon alpha-2a (Roferon, Hoffmann-La Roche brands, Switzerland) in uveitic macular edema refractory to biologic agents. METHODS: Herein, we present two cases of non-infectious uveitis with cystoid macular edema (CME) who were unresponsive to immunosuppressant treatment, and whose uveitis and macular edema recurrences were prevented with subcutaneous injections of pegylated interferon α-2a. RESULTS: Two young males (27- and 30-year-old) diagnosed with non-infectious uveitis and CME were on immunosuppressive treatment. Although both received systemic steroids and biologic agents, macular edema persists. After initiation of pegylated interferon alpha-2a (Pegasys, Genentech, USA) CME regressed significantly and did not occur during their follow-ups of 14 and 12 months. CONCLUSION: Pegylated interferon-alpha-2a can be used as an effective alternative to interferon alpha-2a in uveitic macular edema cases, resistant to other immunosuppressive agents.
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Productos Biológicos , Edema Macular , Uveítis , Masculino , Humanos , Adulto , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Resultado del Tratamiento , Uveítis/complicaciones , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Inmunosupresores/uso terapéutico , Interferón alfa-2/uso terapéutico , Tomografía de Coherencia ÓpticaRESUMEN
Introduction: Relentless placoid chorioretinitis (RPC) is a rare, bilateral disease of the retinal pigment epithelium. The clinical course is prolonged and relapsing. No standard treatment has been established to date. The purpose of this case series is to report four cases of RPC in pediatric and young adult patients in which varying treatments were used, comparing them to previously published cases. Methods: A literature review was conducted to investigate currently published presentations and treatment options for RPC. A multicenter retrospective chart review was also performed on four consecutive patients. These patients were diagnosed with RPC because of new chorioretinitis lesions continuing to appear without or despite therapy for 5-36 months (2 patients), with a clinical course prolonged and relapsing, or because of the atypical location of the multiple lesions (>50) extending from the posterior pole to the equator and mid-peripheral retina (all four patients), which were not consistent with other entities like acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. Results: All four cases of RPC received oral or IV steroids acutely, and three of these patients were transitioned to a steroid-sparing agent and biologic therapy: anti-TNF alpha or anti-IL-6. Quiescence of the chorioretinitis lesions was obtained after 7 months, 1 month, and 36 months; however, the latter had issues with treatment adherence. Mycophenolate mofetil was insufficient to control the disease in one patient, but tocilizumab and infliximab thereafter were effective after cessation of adalimumab due to side effects. Adalimumab when started the first month after the presentation was effective in controlling the disease in one patient. After the failure of interferon-alpha-2a, one patient displayed long-term control with infliximab. One patient did not require a steroid-sparing agent after oral prednisone taper as there was no evidence of progression or recurrence. Conclusion: This case series adds to the current knowledge regarding potential treatments for RPC, specifically the use of anti-TNF-alpha treatment and anti-IL-6 tocilizumab. In this case study, relapses of RPC were found among patients on mycophenolate mofetil and interferon-alpha-2a, and one case did not relapse on oral steroids without a steroid-sparing agent. Our findings suggest that adalimumab, infliximab, and tocilizumab may be useful medications to obtain quiescence of RPC.
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Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface neoplasm. Interferon-alpha (IFNα)-2b has been proved to be an effective immunotherapeutic agent to treat OSSN. We have used intralesional and topical (36 µg/ml) pegylated (peg) IFNα-2a to treat a recurrent surgically failed case of OSSN instead of IFNα-2b. In this case report, we have shared our initial experience with the novel use of peg-IFNα-2a to treat OSSN. According to our brief clinical experience, peg-IFNα-2a is nontoxic to ocular surface and has a promising role to treat OSSN.
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Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.
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Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , ADN Viral , Antígenos e de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Cinética , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet's uveitis (BU). Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet's disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables. Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p > 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p < 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p > 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence. Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.
RESUMEN
Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8-24] months with a follow-up of 17[10-38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] µm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] µm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.
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Interferón alfa-2/administración & dosificación , Edema Macular/tratamiento farmacológico , Uveítis/complicaciones , Agudeza Visual , Antineoplásicos/administración & dosificación , Femenino , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Uveítis/diagnósticoRESUMEN
We recently reported the discovery of a novel protein stabilizing dipeptide, glycyl-D-asparagine, through a structure-based approach. As the starting hypothesis leading to the discovery, we postulated a stabilizing effect achieved by binding of the dipeptide to an aggregation prone region on the protein's surface. Here we present a detailed study of the interaction mechanism between the dipeptide and Interferon-alpha-2A (IFN) through the construction of a Markov state model from molecular dynamics trajectories. We identify multiple binding sites and compare these to aggregation prone regions. Additionally, we calculate the lifetime of the protein-excipient complex. If the excipient remained bound to IFN after administration, it could alter the protein's therapeutic efficacy. We establish that the lifetime of the complex between IFN and glycyl-D-asparagine is extremely short. Under these circumstances, stabilization by stoichiometric binding is consequently no impediment for a safe use of an excipient.
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Dipéptidos/metabolismo , Excipientes/química , Interferón alfa-2/metabolismo , Sitios de Unión , Cadenas de Markov , Simulación de Dinámica MolecularRESUMEN
Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been proposed as curative approach for advanced cutaneous T-cell lymphomas (CTCL). Currently, there is no established consensus for the management of disease relapse after alloHSCT. Results: Ten patients, previously treated with multiple lines of systemic treatment, received alloHSCT. Six patients had achieved partial response (PR, N = 5) and complete response (CR, N = 1) prior to HSCT. Post-HSCT, seven patients (N = 7) relapsed after a median time of 3.3 months (0.5-7.4 months) and were subsequently treated with radiotherapy (RT, N = 1), RT and adoptive T-cell transfer with EBV specific cells (N = 1), R-CHOP (N = 1) and interferon alpha-2a combined either with donor lymphocyte infusion (N = 1) or with brentuximab-vedotin (N = 1). One patient (N = 1) achieved PR only after reducing the immunosuppression. Two patients relapsed again and received interferon alpha-2a and brentuximab-vedotin, respectively. After a median follow-up time of 12.6 months (3.5-73.7 months) six patients were alive (60%) and four had deceased, three (N = 3) due to CTCL and one (N = 1) due to GVHD. Conclusion: Disease relapse after alloHSCT can be controlled with available treatments. For most patients who ultimately relapsed, reduction of immunosuppression and interferon alpha-2a either administered alone or in combination with another systemic agent were preferred. Although interferon alpha-2a, similarly to immunosuppression reduction, may be beneficial for the achievement of graft-vs.-lymphoma effect, the risk of simultaneous worsening of GVHD must be carefully evaluated and taken into consideration.