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Background: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2 V617F , causing constitutive activation of the kinase and activation of downstream signalling. Fedratinib is an oral selective JAK2 inhibitor. It has shown activity in MF and is well-tolerated, but combination with other therapies is likely needed to achieve clonal remission. Combining a JAK2 inhibitor with an interferon may be synergistic, as haematopoietic cells are activated from quiescence (a typical kinase resistance mechanism) rendering them more sensitive to inhibition. Ropeginterferon alfa-2b is a next generation pegylated interferon-α-2b with high tolerability and clinical activity in patients with MF, however, evidence of tolerability and activity in combination with fedratinib is lacking in this setting. The aim of the FEDORA trial is to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b in patients with MF who require treatment to justify further investigation in a phase III trial., Methods: FEDORA is a single arm, multicentre, open-label, Bayesian phase II trial to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b aiming to recruit 30 patients. Patients with JAK2 V617F positive primary or secondary MF, who are aged ≥ 18 years, have intermediate-1 with palpable splenomegaly of > 5cm, intermediate-2, or high-risk disease according to the Dynamic International Prognostic Scoring System (DIPSS), and who require treatment are eligible. The primary outcome is tolerability, whereby the combination is deemed intolerable in a patient if drug-related toxicities in the first four months of treatment lead to: either drug being discontinued; delays in treatment exceeding 28 consecutive days; or death. FEDORA uses a within-patient dose escalation regimen to ensure each patient reaches a personalised dose combination that is acceptable., Discussion: FEDORA is using a Bayesian trial design and aims to provide evidence of the tolerability, safety, and activity of combining fedratinib with ropeginterferon alfa-2b upon which the decision as to whether a phase III trial is warranted will be based., Trial Registration: EudraCT number: 2021-004056-42., Isrctn: 88,102,629., Competing Interests: Declarations. Ethics approval and consent to participate: The trial is being performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland, 1964, amended by the 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996. The protocol (currently v4.0, dated 10-May-2023) was initially approved by the Yorkshire & The Humber—Leeds West Research Ethics Committee on 07-Jan-2022 (Ref. 21/YH/0300). Approval was also granted by the Medicines and Healthcare Products Regulatory Agency on 28-Jan-2022. The FEDORA Trial Office coordinates and communicates protocol modifications to all relevant parties. Consent for publication: Not applicable. Competing interests: MFM has participated in advisory boards for Novartis, BMS, Incyte and GSK, and has received speakers bureau from Novatis, AOP Health, and Incyte. All other authors declare no competing interests., (© 2025. The Author(s).)

Ropeginterferon alfa-2b (ropegIFN), a new-generation interferon-based agent, has been approved in Japan for patients with polycythemia vera (PV) who are ineligible for or respond inadequately to conventional treatment. However, long-term outcomes with ropegIFN in Japanese patients have not been reported. This extension of a phase 2 study of ropegIFN in Japanese patients with PV aimed to determine its long-term safety/efficacy, and changes over time in JAK2 V617F allele burden. Here, we report data from the phase 2 study and subsequent extension over a period of 36 months. The primary endpoint was the complete hematologic response (CHR) maintenance rate without phlebotomy (hematocrit value < 45% without phlebotomy during the previous 12 weeks, platelet count ≤ 400 × 10 9 /L, and white blood cell count ≤ 10 × 10 9 /L). The CHR maintenance rates were 8/27 (29.6%), 18/27 (66.7%), and 22/27 (81.5%) at 12, 24, and 36 months, respectively. No thrombotic or hemorrhagic events occurred. The median allele burden change from baseline was - 74.8% at 36 months. All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36 months in Japanese patients with PV., Competing Interests: Declarations. Conflict of interest: KK reports honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie G.K., Novartis Pharma K.K., PharmaEssentia Japan KK, Sanofi K.K., and Takeda Pharmaceutical Co., Ltd. YS reports research funding from Astellas Pharma Inc., Incyte Biosciences Japan G.K., Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., and Toyo Kohan Co., Ltd.; grants from Shojunkai Takeuchi Hospital; honoraria from Novartis Pharma K.K.; and participation on a data safety monitoring board or advisory board for Novartis Pharma K.K. AG reports research funding from Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., MSD K.K., Nihon Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; consulting fees from Alexion Pharmaceuticals, Inc., Chugai Pharmaceutical Co., Ltd., and PharmaEssentia Japan KK; honoraria from Alexion Pharmaceuticals, Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Kirin Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; and participation on a data safety monitoring board or advisory board for Alexion Pharmaceuticals, Inc., Chugai Pharmaceutical Co., Ltd., and PharmaEssentia Japan KK. KT reports research funding and consulting fees from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., PharmaEssentia Japan KK, and Takeda Pharmaceutical Co., Ltd.; and honoraria from Alexion Pharmaceuticals, Inc., Kyowa Kirin Co., Ltd., MSD K.K., and Novartis Pharma K.K. M Ichii reports payments for presentations from Novartis Pharmaceuticals and payments for speakers bureaus from Sumitomo Pharma Co., Ltd. TI reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Asahi Kasei Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and PharmaEssentia Japan KK. SS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie G.K., Amgen K.K., Asahi Kasei Pharma Co., Ltd., Novartis Pharma K.K., and Ono Pharmaceutical Co., Ltd. M Ito reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Incyte Biosciences Japan G.K., Janssen Pharmaceutical K.K., Novartis Pharma K.K., PharmaEssentia Japan KK, and Takeda Pharmaceutical Co., Ltd. OZ is an employee of PharmaEssentia Corporation USA. AQ is an employee of PharmaEssentia Corporation Taiwan. HK is an employee of PharmaEssentia Japan KK. TS is a board member of PharmaEssentia Japan KK. NK reports grants from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Perseus Proteomics Inc., PharmaEssentia Japan KK, and Sumitomo Pharma Co., Ltd.; research funding from Meiji Seika Pharma Co., Ltd. and Takeda Pharmaceutical Co., Ltd.; consulting fees from Japan Tobacco Inc., PharmaEssentia Japan KK, and Torii Pharmaceutical Co., Ltd.; honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis Pharma K.K. and Takeda Pharmaceutical Co., Ltd.; and is a board member of PharmaEssentia Japan KK. KS reports research funding from AbbVie G.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; honoraria from Novartis Pharma K.K. and Takeda Pharmaceutical Co., Ltd.; and participation on a data safety monitoring board or advisory board for AbbVie G.K., (© 2024. The Author(s).)

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma., Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF., Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment., Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline ( p  < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline ( p  < 0.001) and after 3 months ( p  < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred., Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

The study employed network Meta-analysis to evaluate the efficacy and safety of Chinese patent medicines combined with recombinant human interferon α-2b(interferon) in the treatment of cervical human papillomavirus(HPV) infections. The relevant randomized controlled trial(RCT) published from inception to May 8, 2024 were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science. The modified Jadad scale and the Cochrane risk of bias tool were used to evaluate the quality of the included studies, and RevMan 5.4, R 4.3.3, and Stata 17 were used for data analysis. A total of 105 RCTs were included, involving 12 732 participants and 7 Chinese patent medicines: Baofukang Suppository, Compound Seabuckthorn Seed Oil Suppository, Huangqi Shengmai Decoction, Kangfu Gel, Kangfuyan Capsules, Kushen Gel, and Puling Penyankang Granules. Network Meta-analysis yielded the following results:(1)For improving the negative conversion rate of HPV, SUCRA top-ranked intervention was Puling Penyankang Granules + interferon.(2) For shortening vaginal discharge time, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(3) For reducing the serum level of hypersensitive C-reactive protein(hs-CRP), SUCRA top-ranked intervention was Baofukang Suppository + interferon.(4) For elevating the serum level of CD~+&#95;4 T cells, SUCRA top-ranked intervention was Baofukang Suppository + interferon.(5) For elevating the serum level of CD~+&#95;8 T cells, SUCRA top-ranked intervention was Kangfuyan Capsules + interferon.(6) For improving the CD~+&#95;4/CD~+&#95;8 ratio, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(7)In terms of reducing serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), recurrence rate at 6 months after treatment, and incidence of adverse events, there were no significant differences between the interventions when compared pairwise. The cluster analysis revealed that Puling Penyankang Granules + interferon, Baofukang Suppository + interferon, Kangfu Gel + interferon, and Huangqi Shengmai Decoction + interferon simultaneously improved the negative conversion rate of HPV and reduced the incidence of adverse events. The findings suggested that Chinese patent medicines combined with interferon were effective in treating cervical HPV infection by enhancing the negative conversion rate, shortening the vaginal discharge time, and improving the levels of hs-CRP and T lymphocyte subsets. However, due to the limitations of sample size and quality of the included studies, these conclusions require further validation by studies with larger sample sizes and higher quality.

Purpose of Review: Peyronie's disease characterizes a condition in which there is angular curvature of the penis. We know that the most patients with Peyronie's disease will not have spontaneous resolution of their penile curvature. As such, patients who desire treatment can elect for either surgical or nonsurgical therapy. Herein, we discuss the contemporary nonsurgical management options for Peyronie's disease., Recent Findings: Nonsurgical management options for Peyronie's disease include oral therapy, intra-lesional injections, and penile traction therapy. At the time of this review, there is essentially no high-level evidence demonstrating any benefit for oral therapy. Penile traction therapy has evolved over the past decade with second-generation devices demonstrating strong efficacy and more convenient treatment regimens. Intra-lesional options include collagenase Clostridium histolyticum (CCH), verapamil, and interferon alpha-2b. The IMPRESS trial garnered the strongest level of evidence (two randomized, double-blind, placebo-controlled trials) to support the safety and efficacy of CCH. Verapamil is an option supported by several urological societies; however, the evidence supporting its efficacy is inconsistent between several notable series and randomized studies. IFN alpha 2b can produce modest improvement in curvature, however, is not available for use in North America., Summary: Herein, we will discuss notable advances in nonsurgical management of Peyronie's disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence., Methods: This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method., Results: In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7 mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119)., Conclusions: interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery., Competing Interests: Declarations. Ethical approval: After obtaining written permission from the Vice-Chancellor of Research and Technology of Gilan University of Medical Sciences and the permission of the ethics committee with the code IR.GUMS.REC.1400.411 and also registering in the clinical trial database of Iran with the code IRCT20160919029871N5 by obtaining written informed consent and explaining the objectives of the participants. The study was conducted to assure the confidentiality of the information and that none of the participants would be identified. All project stages during the research period adhered to the principles of the Helsinki Convention. Financial support: This study was funded by Gilan University of Medical Sciences and no other persenoal or governmental funding were included. Conflict of interest: There is no conflict of interest for any author in the present study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy., Methods: In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance ., Results: By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance., Conclusion: Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance., (© 2024. The Author(s).)

Purpose: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient., Case Description: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision., Discussion: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity., Conclusion: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α., Methods: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m 2 , subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored., Results: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment., Conclusions: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB., (© 2024. The Author(s).)

Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV., (© 2024. The Author(s).)

Purpose: To elucidate the efficacy and safety profile of interferon α-2b in vernal keratoconjunctivitis (VKC)., Methods: In this prospective interventional study, VKC patients fulfilling the inclusion and exclusion criteria were included and their signs and symptoms were scored based on the Clinical Scoring System. Patients were treated with topical interferon α-2b eye drop (1 MIU/ml) QID dosing for 6 weeks. Changes in symptoms and signs were evaluated at 2, 4, 8 weeks and 6 months after initiating treatment. A higher score meant severe disease, and a decline in score meant improvement in clinical signs and symptoms. Categorical variables were presented in number and percentage (%) and continuous variables as mean ± standard deviation (SD). Post-medication total subjective symptom score (TSSS) and total objective sign score (TOSS) were compared with baseline, and a P- value of <0.05 was considered significant. Possible ocular and systemic complications were evaluated., Results: The study included 40 patients (32 male and eight female) with a mean age of 8.05 ± 2.33 years. Mean baseline TSSS and TOSS were 6.71 ± 0.564 and 6.59 ± 0.262, respectively, which reduced to 2.71 ± 0.011 ( P = 0.040) and 2.96 ± 0.210 ( P = 0.032), respectively, at 4 weeks and further reduced to 0.42 ± 0.552 and 0.47 ± 0.434, respectively, at 8 weeks. After 6 months of stopping the drug, mean TSSS and TOSS did increase to 2.80 ± 0.820 ( P = 0.044) and 2.50 ± 0.520 ( P = 0.030), respectively, but was still statistically significant improvement compared to the baseline. Also, no ocular or systemic side effects were observed anytime during the study period., Conclusion: Eye drop interferon α-2b (1 million IU/ml) is a safe and effective option as first-line monotherapy for VKC. No side effects and recurrence were observed for 6 months., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon ® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon ® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

Aims: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV)., Methods: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs)., Results: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance., Conclusions: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China., (© 2024 British Pharmacological Society.)

Background: Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients., Objective: To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC., Methods: Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented., Results: This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent., Study Limitations: Observational cohort design without a control group for comparison., Conclusions: Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5-30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4-20.6%) and 3.9% (95%CI, 0.0-17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2-91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4-95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5-77.0%) and 10.4% (95%CI, 3.6-17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Zhang, Xu, Wang, Yan, Chen, Chen, Han, Wang, Wang, Zhao, Qin, Chang, Liu, Huang and Mo.)

Introduction: Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. We aimed to compare the efficacy BCG plus interferon a-2b (BCG/IFN) and Gem/Doce in patients with recurrent NMIBC after a single prior BCG course., Methods: The National Phase II BCG/IFN trial database and multi-institutional Gem/Doce database were queried for patients with recurrent NMIBC after one prior BCG induction course, excluding those with BCG unresponsive disease. Stabilized inverse probability treatment weighted survival curves were estimated using the Kaplan-Meier method and compared. Propensity scores were derived from a logistic regression model. The primary outcome was recurrence free survival (RFS); secondary outcomes were high-grade (HG) RFS and risk factors for treatment failure., Results: We identified 197 BCG/IFN and 93 Gem/Doce patients who met study criteria. Patients receiving Gem/Doce were older and more likely to have HG disease, CIS, and persistent disease following induction BCG (all P < 0.01). After propensity score-based weighting, the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doce (P = 0.95). Adjusted 1- and 2-year HG-RFS was 60% and 51% after BCG/IFN versus 63% and 42% after Gem/Doce (P = 0.68). Multivariable Cox regression revealed that Gem/Doce treatment was not associated with an increased risk of failure (HR = 0.97, P = 0.89) as compared to BCG/IFN., Conclusion: Patients with recurrent NMIBC after a single induction BCG failure and not deemed BCG unresponsive had similar oncologic outcomes with Gem/Doce and BCG/IFN in a post-hoc analysis. Additional prospective studies are needed., Competing Interests: Conflict of interest AMK reports financial interest and/or other relationship with Merck, BMS, Arquer, MDxHealth, Photocure, Theralase, Medac, Asieris, Abbott Molecular and US Biotest. MAO reports financial interest and/or other relationship with Abbott Molecular, Photocure, UroGen, Tocogen, Cold Genesys, Medical Enterprises, Fidia Pharmaceuticals, Vaxiion Pharmaceuticals, Ferring Pharmaceuticals, Sesen Bio, Urovant and Theralase. VTP reports financial interest and/or other relationship with Cold Genesys. MK reports being an advisory boards member for Genesis Biotech and Janssen; consultant for Pacific Edge, Fergene. All other authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hydroxyurea (HU) treatment of patients with essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (MPNs) normalizes elevated blood cell counts within weeks in the large majority of patients. Studies on the impact of HU upon the kinetics of the JAK2V617F allele burden, leukocyte, and platelet counts over time are scarce., Purpose: Using data-driven analysis as a novel tool to model the kinetics of the JAK2V617F allele burden and blood cell counts over time during treatment with HU., Material and Methods: Using serial measurements of JAK2V617F and correlation analysis of routine hematological values (the Hb-concentration, leukocyte count, platelet count, and lactic dehydrogenase), we present a detailed description and analysis of the kinetics of the JAK2V617F, leukocyte, and platelet counts and lactic dehydrogenase in 27 patients (PV = 18; ET = 7; PMF = 2), who were followed in the Danish randomized trial (DALIAH). To further analyze the JAK2V617F kinetics, we use a machine learning clustering algorithm to group the response patterns., Results: Response patterns were highly heterogeneous, with clustering resulting in 3 groups and 3 outliers. In the large majority of patients, HU treatment was initially associated with a modest decline in the JAK2V617F allele burden in concert with a decline in leukocyte and platelet counts. However, HU did not induce a sustained and continuous decrease in the JAK2V617F allele burden., Conclusion: Using data-driven analysis of the JAK2V617F allele burden, leukocyte, and platelet kinetics during treatment with HU, we have shown that HU does not induce a sustained decrease in the JAK2V617F allele burden and neither induces sustained normalization of elevated cell counts in MPN patients. Our results may explain why MPN patients during treatment with HU still have a substantially increased risk of thrombosis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism., Material and Methods: A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12 th to 24 th , 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21., Results: A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission ( p  < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped ( p =  .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group ( p =  .3152)., Conclusions: IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.

Purpose: To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status., Methods: Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b., Results: There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes., Conclusions: Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma., Patients and Methods: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m 2 /day i.v., 5 days per week for 4 weeks, then 10 MU/m 2 /day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery., Results: A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 27.3-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR ( P = 0.002 and P = 0.008, respectively)., Conclusions: Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator. See related commentary by Menzies et al., p. 4133 ., (©2021 American Association for Cancer Research.)

Objectives: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease., Methods: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes., Results: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred., Conclusions: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We sought to compare the efficacy and safety of conjunctival autograft (CAG), amniotic membrane transplantation (AMT) with postoperative interferon alfa-2b (IFN alfa-2b), and modified conjunctival autograft plus amniotic membrane transplantation (mCAG plus AMT) with postoperative IFN alfa-2b for primary pterygium., Design: Randomized controlled clinical trial., Methods: Eyes with nasal and primary pterygia were randomized in a 1:1:1 ratio to receive CAG, AMT with IFN alfa-2b, or mCAG plus AMT with IFN alfa-2b. Subjects were followed up for 12 months. Primary outcomes included recurrence rate and complications. Secondary outcomes included corneal epithelium status, ocular surface symptom score, and visual acuity change., Results: Eighty-five subjects (30 in the CAG group, 25 in the AMT group, and 30 in the CAG+AMT group) completed the 12-month follow-up. No complication or grade 4 recurrence was found. There was no significant difference among the 3 groups in recurrence grade, corneal epithelium status, and visual acuity change. Compared with mCAG+AMT, CAG has a negative effect (β = -0.62, P = .001), and AMT has a negative effect (β = -2.02, P < .001) on postoperative symptom scores. Compared with AMT, CAG has a positive effect (β = 1.28, P < .001) on postoperative symptom scores., Conclusions: All 3 strategies had good safety and clinical efficacy in the study. Compared with conjunctival autograft, the 2 surgeries using no autograft or limited autograft was less traumatic and gave more flexibility for future ocular surface condition changes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Objectives: Ropeginterferon alfa-2b is a novel monopegylated recombinant interferon alfa-2b for the treatment of patients with polycythemia vera. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of ropeginterferon alfa-2b in healthy Japanese subjects compared with Caucasian subjects., Methods: In this multicenter, parallel-group phase I study, a cohort consisting of six Japanese and six Caucasian subjects was designated to receive a single subcutaneous dose of ropeginterferon alfa-2b (100, 200, 300, and 450 µg). Pharmacokinetic and pharmacodynamic parameters, and immunogenicity were evaluated. Safety was assessed throughout the study., Results: Cohort 4 (450-µg dose) was not initiated because the primary objective of this study was achieved based on the three completed cohorts. A total of 36 enrolled subjects (18 Japanese and 18 Caucasian) in three cohorts were included in the safety, pharmacokinetic, and pharmacodynamic analysis sets. Ropeginterferon alfa-2b exposure in terms of the area under the serum concentration-time curve (AUC) from time zero extrapolated to infinity and the AUC from time zero to the time of the last quantifiable concentration was approximately 1.7-fold and two-fold higher in Japanese subjects than in Caucasian subjects, respectively. Across the same dose range, the maximum serum concentration was approximately 1.25-fold higher in Japanese subjects than in Caucasian subjects. The time to reach the median maximum serum concentration was similar between ethnicities (approximately 96-111 h). The terminal half-life was 48-57 h in Japanese subjects and 31-75 h in Caucasian subjects. The slope of the relationship between dose and drug exposure was greater than 1 in both ethnicities. The dose-dependent induction of beta-2 microglobulin and neopterin expression was observed in both ethnicities, and the two groups showed similar pharmacodynamic parameters. At the end of the study, 22.2% of Japanese subjects and 11.1% of Caucasian subjects developed anti-ropeginterferon alfa-2b-binding antibodies. The neutralizing capacity of these antibodies was not tested. Ropeginterferon alfa-2b up to 300 µg was safe and well tolerated, with no unexpected safety findings based on previous experiences with ropeginterferon alfa-2b and other forms of interferon., Conclusions: Ropeginterferon alfa-2b exposure was higher in Japanese subjects than in Caucasian subjects. The increase in ropeginterferon alfa-2b exposure was greater than the dose proportion in the dose range of 100-300 µg. Ropeginterferon alfa-2b was safe and well tolerated., Clinical Trial Registration: ClinicalTrials.gov identifier NCT03546465, registered on 6 June, 2018.

The combination of Interferon-&alpha;-2b (IFN-&alpha;-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.

A man with a history of blind eye due to trauma 22 years earlier consulted at 53 years of age with a large conjunctival neoplastic lesion, compromising almost the entire temporal limbus, and reaching a size of approximately 16 mm on its larger diameter, in the conjunctiva. Management was started with topical and subconjunctival chemotherapy (interferon alpha-2b) in order to perform immunoreduction, but a dramatic response with total disappearance of the lesion was observed. In the follow-up time period of more than 7 years, there were no signs of recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm (MPN). A newly developed PV treatment option, ropeginterferon alfa-2b, contains recombinant human alfa monoisomer as an active ingredient, resulting in a novel pharmacologic profile and improved tolerability. Efficacy studies conclude remarkable long-term hematological response and sustained JAK2V617F allele burden reduction. Ropeginterferon alfa-2b compound has been approved for the treatment of polycythemia vera without symptomatic splenomegaly., Areas Covered: Current clinical trials are investigating the role of ropeginterferon alfa-2b in the first-line setting of treatment for PV. The safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues are also discussed of ropeginterferon alfa-2b., Expert Opinion: Ropeginterferon alfa-2b is a targeted therapeutic option in the treatment of PV, representing a significant improvement compared to conventional cytoreductive therapies. The single isomer entity of the recombinant human interferon alfa-2b and the mono-pegylation method imparts favorable properties to the compound. The use of ropeginterferon alfa-2b allows extended dosing interval, reduces side effects, and may increase the overall survival of PV patients by reducing the risk of progression to myelofibrosis or acute leukemia. Clinical data suggests that the compound may provide a disease-modifying option for PV patients with asymptomatic splenomegaly.

Background: Pegylated interferon (PEG-IFN) has recently been approved for the treatment of chronic hepatitis B in children and adolescents. However, the exact efficacy and safety remains to be confirmed., Objectives: A systematic review and meta-analysis was performed to assess the efficacy and safety of PEG-IFN for the treatment of chronic hepatitis B in children and adolescents., Methods: Databases including MEDLINE/PubMed, Ovid-EMbase, the Cochrane Library and China National Knowledge Internet were searched to collect clinical trials examining the efficacy and safety of PEG-IFN in children and adolescents with confirmed hepatitis B virus infection. Data for treatment response, relapse, treatment discontinuations and adverse events were extracted and summarized., Results: A total of 10 clinical trials involving 658 patients were identified. Results indicate that 43% (95% confidence interval [CI]: 25%-61%) of the subjects treated with PEG-IFN achieved HBeAg serologic response, 18% (95% CI: 6%-35%) achieved HBsAg serologic response, 68% (95% CI: 55%-79%) achieved virologic response after the end of treatment and 60% (95% CI: 30%-87%) achieved sustained virologic response., Conclusion: Current evidence indicates that PEG-IFN is effective in children and adolescents with hepatitis B virus and that treatment discontinuation due to serious adverse events is infrequent.

The goal of current management of patients with chronic phase chronic myeloid leukemia (CML) is to reach treatment-free remission with sustained deep molecular remission (DMR) being the prerequisite therefor. Second-generation tyrosine kinase inhibitors can induce deeper and faster remission than imatinib, but are often associated with severe adverse events (AEs). The combination of pegylated interferon (IFN) with imatinib was shown to induce higher molecular remissions than imatinib alone in two studies. Treatment discontinuation rates due to IFN induced AEs were high in both studies. To investigate safety, tolerability (primary objective), and efficacy (secondary objective) of the combination of imatinib with ropeginterferon alpha-2b this phase I study was initiated. Twelve patients were planned to be enrolled. Nine patients completed the study according to protocol. Three patients terminated the study early, one due to occurrence of a dose-limiting toxicity (neutropenia grade 3), one due to an AE (panic attacks grade 2) and one due to the patient's decision. Tolerability was good, non-hematologic AEs were mainly grade 1/2, hematologic AEs were mainly neutropenias. No new AEs were reported for the combination of imatinib and ropeginterferon alpha-2b. In a nondose-dependent manner the addition of ropeginterferon alpha-2b led to the achievement of a DMR in four out of nine patients after a treatment duration of 18 months. The combination of imatinib and ropeginterferon alpha-2b is safe and showed in this phase I study the ability to deepen the molecular response in patients with chronic phase CML not achieving a DMR with imatinib alone., (© 2020 John Wiley & Sons Ltd.)

Background: The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone., Methods: Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b., Results: A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups., Conclusions: Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.

Rituximab monotherapy is widely used for follicular lymphoma. However, there are no established predictors for response or response duration. We analyzed the long-term prognostic relevance of pre-treatment absolute blood counts of lymphocytes with subsets and monocytes in 265 follicular lymphoma patients, uniformly treated with rituximab without chemotherapy, in two Nordic Lymphoma Group trials. There were 265 previously untreated, stage II-IV follicular lymphoma patients with a median follow-up of over 10 years. Absolute B cell counts ≥ median (0.09 × 10 9 /L) were an independent predictor for shorter time to next treatment or death (multivariable analysis P = 0.010). In univariate analysis, absolute monocyte counts ≥ median (0.5 × 10 9 /L) did not correlate with time to next treatment or death, but with inferior overall survival (P = 0.034). Absolute T cell or T cell subset counts were not predictive for outcome. High absolute B cell counts, possibly reflecting circulating lymphoma cells, have an unfavorable impact on time to next treatment or death in patients treated with rituximab without chemotherapy.

Background and Aim: Single-nucleotide polymorphisms (SNPs) of the interleukin-28B (IL-28B) gene are associated with the effectiveness of interferon therapy for chronic hepatitis C infection. Whether the IL-28B genotype affects the course of treatment and the outcomes of patients with advanced hepatocellular carcinoma (HCC) is unknown., Methods: We detected the IL-28B SNP (rs8099917) using TaqMan PreDesigned SNP Genotyping Assays to assess the effects of the IL-28B genotype on treatment efficacy and prognosis of patients with advanced HCC treated with hepatic arterial infusion chemotherapy (HAIC) between September 2003 and January 2015., Results: The study included 154 patients who received HAIC to treat advanced HCC, among which 27 (17.5%) had the minor genotype, IL-28B rs8099917 TG or GG, and the others had the major genotype, IL-28B rs8099917 TT. The objective response rates of patients with the minor or major genotype were 51.9% and 29.1% (P = 0.022), respectively. Multivariate analysis revealed that the minor genotype remained associated with the response to HAIC (odds ratio, 2.620; P = 0.026). The median overall survival of patients with major or minor genotypes was 14.1 and 16.9 months, respectively, and the overall survival of patients with the major genotype was significantly shorter than that of patients with the minor genotype (P = 0.027). Multivariate analysis revealed that the major genotype was an independent, unfavorable prognostic factor (hazard ratio, 1.720; P = 0.024). Consistent results were obtained in selected populations after propensity score matching analysis., Conclusions: The IL-28B SNP (rs8099917) will serve as a useful predictor of the outcomes of patients with advanced HCC treated with HAIC., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development., Methods: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors., Results: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206)., Conclusions: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Rationale: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The initial epidemiological investigations showed that COVID-19 occurred more likely in adults, with patients younger than 10 years old accounting for less than 1% of the total number of confirmed cases, and infant infections were more rare. In our case, we present an infant who was only 35 days old when he was tested positive for COVID-19., Patient Concerns: In this report, a 35 day-old male infant with atypical symptoms had close contact with 2 confirmed patients of COVID-19 who were his grandmother and mother., Diagnosis: The patient was diagnosed as COVID-19 after his oropharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcription-polymerase chain reaction assay., Interventions: The therapeutic schedule included aerosol inhalation of recombinant human interferon α-2b and supportive therapy., Outcomes: Two consecutive (1 day apart) oropharyngeal swabs tested negative for severe acute respiratory syndrome coronavirus 2; then, the patient was discharged on February 27, 2020., Lessons: Strengthening infants' virus screening in families with infected kins is important for early diagnosis, isolation, and treatment when symptoms are atypical. The infectivity of infants with mild or asymptomatic COVID-19 should not be ignored because this may be a source of transmission in the community.

Background: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79)., Patients and Methods: In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20)., Results: Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32-1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7-88.8%) and 72.9% (95% CI: 58.3-83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15-0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9-96.0%) vs 76.4% (95% CI: 62.1-85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons., Conclusions: The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes., Competing Interests: Conflict of interest statement A.M.M.E. reports receiving personal fees as consultant advisor for Biocad, BioInvent, Bristol Myers Squibb (BMS), CatalYm, Ellipses, Glaxo Smith Kline (GSK), HalioDX, Incyte, IO Biotech, ISA Pharmaceuticals, Nektar, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, Sellas, SkylineDx. P.R. reports receiving personal fees as consultant advisor for Novartis, MSD, BMS, Roche, Pfizer, Blueprint Medicines and Pierre Fabre, outside the submitted work. R.H.-W. reports receiving grants and non-financial support from EORTC, during the conduct of the study. C.R. reports personal fees as consultant advisor for Roche, Pierre Fabre, Merck, Novartis, Amgen, BMS, Novartis, MSD, Sanofi, Biothera, Ultimovacs, outside the submitted work. A.v.A. reports receiving grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Sanofi and 4SC, outside the submitted work. L.B. reports receiving personal fees as consultant advisor for BMS, Novartis, MSD, Swedish Orphan, Bayer and Incyte outside the submitted work. A.M. reports receiving personal fees from Novartis, Pierre Fabre, MSD and SunPharma, outside the submitted work. J.J.G. reports receiving personal fees for advisory role from BMS, Novartis, MSD, Roche, Amgen,Pierre Fabre, Merck, Pfizer and Sanofi, and has also received travel support from BMS, Novartis, MSD, outside the submitted work. D.S. reports receiving grants, personal fees for consulting or advisory role; received honoraria; received travel expenses, accommodations, expenses from MSD, during the conduct of the study; and also received personal fees for consulting or advisory role; honoraria; travel expenses, accommodations, expenses from Roche / Genentech, personal fees, non-financial support and other from Novartis, grants and personal fees from BMS, personal fees and non-financial support from Merck Serono, and Amgen, personal fees from Immunocore, Incyte, 4SC, Pierre Fabre, Mologen, Sanofi / Regeneron, Roche, Sysmex, Agenus, Array BioPharma, AstraZeneca, InFlarX, Philogen, Nektar, Sandoz, non-financial support from Merck, outside the submitted work. M.M., F.G., E.P., E.M., O.B., S.M., M.K. and S.S. report no competing interests. A.A.E.T. reports receiving travel support from Agenus, outside the submitted work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Eliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly., Methods: The VIETNARMS trial will factorially randomly assign patients to two drug regimens, three treatment-shortening strategies or control, and adjunctive ribavirin or no adjunctive ribavirin with shortening strategies (14 randomly assigned groups). We will use Bayesian monitoring at interim analyses to detect and stop recruitment into unsuccessful strategies, defined by more than 0.95 posterior probability that the true cure rate is less than 90% for the individual randomly assigned group (non-comparative). Final comparisons will be non-inferiority for regimens (margin 5%) and strategies (margin 10%) and superiority for adjunctive ribavirin. Here, we tested the operating characteristics of the stopping guideline for individual randomly assigned groups, planned interim analysis timings and explored power at the final analysis., Results: A beta (4.5, 0.5) prior for the true cure rate produces less than 0.05 probability of incorrectly stopping an individual randomly assigned group with a true cure rate of more than 90%. Groups with very low cure rates (<60%) are very likely (>0.9 probability) to stop after about 25% of patients are recruited. Groups with moderately low cure rates (80%) are likely to stop (0.7 probability) before overall recruitment finishes. Interim analyses 7, 10, 13 and 18 months after recruitment commences provide good probabilities of stopping inferior individual randomly assigned groups. For an overall true cure rate of 95%, power is more than 90% to confirm non-inferiority in the regimen and strategy comparisons, regardless of the control cure rate, and to detect a 5% absolute difference in the ribavirin comparison., Conclusions: The operating characteristics of the stopping guideline are appropriate, and interim analyses can be timed to detect individual randomly assigned groups that are highly likely to have suboptimal performance at various stages. Therefore, our design is suitable for evaluating treatment-shortening or -simplifying strategies., Trial Registration: ISRCTN registry: ISRCTN61522291. Registered on 4 October 2019.

Purpose: The objective of this study is to evaluate the effect of the topical interferon α2b (IFNα2b) as an adjunctive therapy in the treatment of diabetic macular edema., Method: This was a randomized controlled clinical trial performed on patients with diabetic macular edema. Fifty eyes of 50 patients (one eye/patient) who were receiving treatment for diabetic macular edema were randomly assigned to get topical IFNα2b 1 MU/mL or artificial tear eye drop as an adjunctive therapy. The primary measure outcomes were best-corrected visual acuity and central macular thickness; the secondary goals were to assess the effect of topical IFNα2b on the intraocular pressure and its potential side effects., Results: Baseline demographic data of the two groups were similar. The improvement in visual acuity of patients on IFN was more than the patients on artificial tear by the end of the fourth week (6.85 and 1.45 Early Treatment Diabetic Retinopathy Study letters, respectively, P = 0.001) and the eighth week (6.75 and 1.05 Early Treatment Diabetic Retinopathy Study letters, respectively, P = 0.005). The central macular thickness was also decreased correspondingly by the end of fourth week (53.1 ± 153 µm for patients on IFN and 26.6 ± 119.1 µm for patients on artificial tear, P = 0.497) and eighth week (27.9 ± 67.7 for patients on IFN and 29.2 ± 98 µm for patients on artificial tear, P = 0.957), but it was not statistically significant. Intraocular pressure was decreased on the fourth week in IFN group for 1.7 mmHg ±3 and increased for 0.1 mmHg ±2.3 in the artificial tear group (P = 0.018). No significant side effect was detected with topical IFN drop., Conclusion: This study evaluated the short-term effects of topical IFNα2b 1 MU/mL. The drug was well tolerated and may have an effect on improvement of best-corrected visual acuity in patients with diabetic macular edema. It also had an intraocular pressure lowering effect on the studied eyes. However, further studies are needed to confirm this finding.

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is characterized by malignant CD4+ skin-homing T-cells that drive formation of cutaneous patches, plaques, and/or tumors. MF's known immunogenicity makes it an ideal candidate for local immunotherapy. Recombinant human leukocyte interferon-α2 (rIFN-α2) has well-established immunomodulatory, antiproliferative, and antitumor effects; and relatively low levels of endogenous IFN-α have been observed within MF lesions. As a systemic therapy delivered via subcutaneous (SC) or intramuscular (IM) injection, rIFN-α2 has previously shown efficacy against MF. Due to high levels of toxicity associated with the systemic dosing required for improvement of disease, rIFN-α2 has had limited use in the treatment of MF. For these reasons, we sought to deliver rIFN-2 as a local immunotherapy, and herein describe two cases of MF successfully managed with intralesional injections of low-dose rIFN-α2. With limited reporting in the medical literature, intralesional injection of rIFN-α2 has shown efficacy, but with high frequency of associated systemic side effects. Towards a better tolerated, localized immunotherapy, we initiated treatment in two MF patients with low dose (0.5 MU) rIFN-α2 per injection that led to marked responses, and subsequent dosing to 1.0 MU ultimately led to complete resolution of the treated lesions without the generalized side effects observed with systemic administration of rIFN-α2. These cases suggest that low-dose intralesional rIFN-α2 may be an efficacious and well-tolerated local immunotherapy for early stage MF, providing a therapeutic option for the management of chronic, recalcitrant lesions., (Copyright ©2020, Yale Journal of Biology and Medicine.)

Ropeginterferon alfa-2b is a novel mono-PEGylated alfa interferon. It is the first interferon approved for the treatment of patients with polycythemia vera (PV) and the first and only approved treatment for PV independent of previous hydroxyurea exposure. In contrast to other interferons, the drug has to be subcutaneously injected every 2 weeks only, with intervals of 4 weeks being possible after prolonged use. It is generally well tolerated and can lead to deep molecular responses. In this article, we provide a review of available preclinical and clinical data of ropeginterferon alfa-2b leading to its E.U. approval and give an outlook on future clinical trials involving this drug., (Copyright 2020 Clarivate Analytics.)

Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called "needle fatigue", i.e., a waning commitment to continue with the prescribed injectable treatment. Therefore, alternative treatment strategies to enhance patients' adherence are warranted. In this independent, multicentre post-marketing study, we sought to directly compare switching to either teriflunomide (TFN), dimethyl fumarate (DMF), or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up. We analyzed a total of 621 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (n = 265), TFN (n = 160), or PEG (n = 196). Time to discontinuation and time to first relapse were explored in the whole population by Cox regression models adjusted for baseline variables and after a 1:1:1 ratio propensity score (PS)-based matching procedure. Treatment discontinuation was more frequent after switching to PEG (28.6%) than DMF (14.7%; hazard ratio [HR] = 0.25, p < 0.001) and TFN (16.9%; HR = 0.27, p < 0.001). We found similar results even in the re-sampled cohort of 222 patients (74 per group) derived by the PS-based matching procedure. The highest discontinuation rate observed in PEG recipient was mainly due to poor tolerability (p = 0.005) and pregnancy planning (p = 0.04). The low number of patients who relapsed over the 12-month follow-up (25 out of 621, approximately 4%) prevented any analysis on the short-term risk of relapse. This real-world study suggests that oral drugs are a better switching option than low-frequency interferon for promoting the short-term treatment persistence in stable patients who do not tolerate injectable drugs.

Treatment with PEGylated interferon-alpha2 (IFN) of patients with essential thrombocythemia and polycythemia vera induces major molecular remissions with a reduction in the JAK2V617F allele burden to undetectable levels in a subset of patients. A favorable response to IFN has been argued to depend upon the tumor burden, implying that institution of treatment with IFN should be as early as possible after the diagnosis. However, evidence for this statement is not available. We present a thorough analysis of unique serial JAK2V617F measurements in 66 IFN-treated patients and in 6 untreated patients. Without IFN treatment, the JAK2V617F allele burden increased exponentially with a period of doubling of 1.4 year. During monotherapy with IFN, the JAK2V617F allele burden decreased mono- or bi-exponentially for 33 responders of which 28 patients satisfied both descriptions. Bi-exponential description improved the fits in 19 cases being associated with late JAK2V617F responses. The decay of the JAK2V617F allele burden during IFN treatment was estimated to have half-lives of 1.6 year for the monoexponential response and 1.0 year in the long term for the bi-exponential response. In conclusion, through data-driven analysis of the JAK2V617F allele burden, we provide novel information regarding the JAK2V617F kinetics during IFN-treatment, arguing for early intervention., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: To analyze the efficacy and safety of sofosbuvir (SOF)-based regimens in Thai patients with chronic hepatitis C virus infection who had pre-existing significant liver fibrosis., Patients and Methods: This was a retrospective cohort study, conducted between 1 June 2018 and 31 May 2019 at Rajavithi Hospital, Bangkok, Thailand. All patients completed 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) 12 weeks after the end of therapy., Result: A total of 185 patients were included, with 52, 63 and 70 taking SOF+Ledipasvir (SOF+LDV), SOF+LDV+ribavirin (RBV) and SOF+Pegylated interferon (Peg-IFN)+RBV (SOF+Peg-IFN+RBV) respectively. Genotype (GT) 1 was predominant at 40.0%, followed by GT3 at 37.8%, and GT6 at 22.2%. Overall 95.1% of patients in this study achieved SVR (n = 176/185), and the only factor associated with SVR was HCV genotype (p = 0.001). GT6 patients had lower SVR rates compared to GT1 and GT3 patients (82.9%, 98.6%, and 98.6% respectively) while there was no association between SVR and other factors (p >0.05) such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history. No serious adverse events were reported in the present study., Conclusion: Sofosbuvir-based regimens in the treatment of patients with chronic HCV infection were highly efficacious with excellent safety and tolerability profiles in a real-world setting; however, further research is required to establish whether or not such a regimen is an adequate treatment for all genotype 6 patients., Competing Interests: The authors have declared that no competing interests exist.

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.

Purpose : To assess the efficacy and safety of systemic interferon alpha-2a (IFN) for refractory pseudophakic cystoid macular edema (PCME). Methods : Retrospective observational study. The primary outcome was the decrease of central retinal thickness (CRT). Secondary endpoints were the improvement of best-corrected visual acuity (BCVA) and the assessment of IFN-related side effects. Results : Twenty-four eyes of 20 patients were included. The median CRT was 513 µm (range 220-980 µm) at baseline and decreased to 190 µm (range 140-520 µm) at the last follow-up visit (p < 0.001). Reduction of CRT greater than 100 µm was observed in 22 eyes (92%). The median BCVA (logMAR) increased statistically significant from 0.5 (range 0.2-1.5) at baseline to 0.3 (0-0.8) at the last follow-up (p < 0.001). The BCVA improved in 18 eyes (75%) and remained stable in five eyes (21%). No severe treatment-related side effects occurred. Conclusion : IFN is a very effective agent for treatment of refractory PCME.

Aim: To report the clinical course of patients with ocular surface squamous neoplasia treated with topical interferon α-2b (IFNα-2b) after local excision of the tumor., Patients and Methods: This study enrolled four consecutive Japanese patients comprising one eye with conjunctival carcinoma in situ, and three eyes with squamous cell carcinoma (SCC) diagnosed histopathologically. All of them initially visited Hokkaido University Hospital in 2016. After resecting the tumor tissues, topical IFNα-2b eye drops were given to the eye four times a day. This study retrospectively analyzed the ophthalmological and imaging findings before and after the surgery, based on the patients' medical records., Results: The mean follow-up duration was 37.8 months. All cases were males, and the mean age was 62.3 years. The tumor was located in the bulbar conjunctiva in three cases. Local pedunculated rotation flap, and free conjunctival flap were performed in one and two patients, respectively. In one case with SCC, the tumor involved the lower palpebral conjunctiva, already invading into the orbit at the first visit. The patient underwent extended resection of the lower lid, and reconstruction of the posterior lobe of the eyelid with Hughes flap. Cataract surgery was successfully conducted 18 months after tumor resection. All patients remain well without local recurrence or distant metastasis., Conclusion: Topical IFNα-2b treatment contributed to suppression of tumor recurrence and improvement of quality of vision in patients after local resection of ocular surface squamous neoplasia., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)