Interferon Alfa Research Articles

A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with “early/lower-risk PMF”, defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

Retrospective evaluation of "Rods and Rings" pattern detected in the anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) test.

Anti-rods and rings (anti-RR) antibodies have recently been described as a cytoplasmic pattern in IIF-based screening of autoantibodies on HEp-2 cells and ICAP has named it as AC-23. It is most frequently related to drug-induced antibody generation. This study aimed to investigate the clinical significance of AC-23 positivity and its relevance to the diagnosis and/or follow-up of the associated diseases and/or drug use. A multicenter retrospective study was conducted among 10 hospitals from six different provinces in Türkiye from January 2017 to December 2021. The laboratory data and clinical information of 600 patients with positive anti-RR antibodies out of 547.558 HEp-2 IIF ANA samples were analyzed. The distribution of AC-23 positive patients by year indicated a steady increase between 2017-2021. Anti-RR prevalence in post-COVID-19 period was significantly higher than that of pre-COVID-19 period (p=0.00). Concomitant ANA positivity was detected in 56.5% of patients, the most common patterns being AC-4 and AC-5 (41.1%). The most frequent pathology among the anti-RR positive patients was an autoimmune disease (19.83%); 28.57% of which had rheumatoid arthritis and 17.65% autoimmune liver disease. Among the 600 patients, 65 (10.83%) were diagnosed as hepatitis C virus (HCV) infection. Available data for 38 of the HCV patients revealed that 71.05% of them had a history of interferon alfa+ribavirin and 28.95% of them had a history of NS3/4/5A/5B polymerase inhibitor or protease inhibitor drug use. Significant increase in the rate of anti-RR positivity was observed in the post-COVID-19 period when compared to pre-COVID-19 period (p:0.00). This is the first multicenter study in Türkiye about the clinical association of anti-RR antibodies which may be ignored during routine HEp-2 IIF testing. Pathologies other than HCV should be taken into consideration in terms of the possible role of anti-RR in autoimmune diseases and other pathologies. The preliminary data obtained in this study suggest that anti-RR antibody development might also be associated to COVID-19, supporting the several previous data related to the potential of viruses triggering the formation of autoantibodies. Large-scale prospective studies should elucidate the clinical significance of RR pattern and determine its role in patient diagnosis and follow-up.

PD-1 inhibitors versus conventional therapies for adjuvant treatment of resected acral melanoma: A systematic review and meta-analysis.

e21555 Background: Acral melanoma (AM) is a rare and aggressive melanoma subtype with unique characteristics in western Caucasian population, but mostly prevalent in Asian population. FDA has approved pembrolizumab and nivolumab for the adjuvant treatment of melanoma. However, its role in AM is still unclear. In US and mainland of China, high-dose interferon alfa was once approved, while in other part of the world, there was no standard treatment for adjuvant therapy of AM. Thus, we performed a meta-analysis to summarize the efficacy of anti-PD-1 monotherapy in patients with AM in adjuvant setting and derive implications for early-stage AM management. Methods: A systematic review of electronic databases was conducted to identify studies that assessed relapse-free survival (RFS) and overall survival (OS) between adjuvant PD-1 and conventional therapy (interferon (IFN) / chemotherapy) or observation alone in patients with AM. RFS was the primary endpoint, OS was the secondary endpoint. We estimated RFS/OS using the fixed-effect model. Statistical analyses in our study were carried out using Stata 12.0 (Stata Corp LP, College Station, TX, USA). Results: Five retrospective studies that totally involving 516 patients with AM were recruited, including 3 China studies and 2 non-China studies. Among them, there were 260 PD-1, 74 IFN, 178 OBS and 4 chemotherapy, respectively. Adjuvant PD-1 inhibitor achieved better efficacy than conventional therapy, showing significant improvement both in RFS (HR 0.76, 95%Cl 0.61-0.95) and OS (HR 0.57 0.37-0.88). This trend of RFS/OS benefit was observed in all subgroups, includes control treatment (OBS/IFN) or study region (China/non-China). Conclusions: Our data supports that patients with resected AM are more likely to derive benefit from adjuvant PD-1 comparing to conventional treatment or observation alone. Perspective studies are warranted to explore the role of adjuvant PD-1 in AM. [Table: see text]

Long-term antiviral therapy is associated with changes in the profile of transcriptionally active HBV integration in the livers of patients with CHB.

Hepatitis B virus (HBV) integration exists throughout the clinical course of chronic hepatitis B (CHB). This study investigated the effects of long-term antiviral therapy on the level and profiles of transcriptionally active HBV integration. Serial liver biopsies and paired blood samples were obtained from 16, 16, and 22 patients with CHB at baseline, 78, and 260 weeks of entecavir monotherapy or combined with pegylated interferon alfa, respectively. Serum HBV biomarkers were longitudinally assessed. RNA-seq and HIVID2 program was used to identify HBV-host chimeric RNAs transcribed from integrated DNA. The counts of HBV integration reads were positively related to both serum HBV DNA levels (r = 0.695, p = 0.004) and HBeAg titers (r = 0.724, p = 0.021) at baseline, but the positive correlation exited only to the serum HBsAg levels after 260 weeks of antiviral therapy (r = 0.662, p = 0.001). After 78 weeks of antiviral therapy, the levels of HBV integration expression decreased by 12.25 folds from baseline. The viral junction points were enriched at the S and HBx genes after the long-term antiviral therapy. HBs-FN1 became one of the main transcripts, with the mean proportion of HBs-FN1 in all integrated expression increased from 2.79% at baseline to 10.54% at Week 260 of antiviral treatment. Antiviral therapy may reduce but not eliminate the HBV integration events and integration expression. Certain integration events, such as HBs-FN1 can persist in long-term antiviral treatment.

Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials

Background & Aims: Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies. Approach & Results: Pre-treatment, on-treatment, and post-treatment sera from 61 immunotolerant trial participants on PegIFNα/entecavir therapy and 88 immune active trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by preincubation of sera±recombinant human IFNα added to Huh7 cells with the measurement of interferon-stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated. Preincubation of on-treatment serum from 26 immunotolerant (43%) and 13 immune active (15%) participants with recombinant-human IFNα markedly blunted ISG-induction in Huh7 cells. The degree of ISG inhibition correlated with IFNα antibody titer (p < 0.0001; r = 0.87). On-treatment development of anti-IFNα neutralizing antibodies (nAbs) was associated with reduced quantitative HBsAg and qHBeAg declines (p < 0.05) and inhibited IFNα bioactivity to 240 weeks after PegIFNα cessation. Children developed anti-IFNα nAbs more frequently than adults (p = 0.004) but nAbs in children had less impact on virological responses. Conclusions: The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for the optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.

Treatment results of our patients with acute viral hepatitis C

Aim: The diagnosis of acute hepatitis C virus (HCV) infection can be made during follow-up in patients with a generally known risk contact, as it is mostly asymptomatic. The earliest indicator of acute HCV infection is increased HCV-RNA. Anti-HCV seroconversion is also the strongest evidence of acute infection. The risk of chronicity is at least 80%. Treatment of acute HCV infection is recommended because of the high rate of chronicity. Spontaneous recovery can be seen after 8-12 weeks in acute viral hepatitis C. Therefore, 8-12 weeks should be waited to start specific treatment. The aim of this study is to evaluate the data of the patients we follow up with the diagnosis of acute HCV in our clinic, to determine the most appropriate time to start treatment in acute viral hepatitis C and to evaluate the effectiveness of Peg-interferon alfa 2a treatment.
 Materials and Methods: The data of patients diagnosed with acute viral hepatitis C in our clinic between 2005 and 2015 were evaluated.
 Results: Twelve patients with acute viral hepatitis C were followed in our clinic. Twelve of the cases were male, and the mean age was 38.83 ± 6.75 (range, 25-50) years. Spontaneous clearance was observed in three patients at the third month. Three months after the acute diagnosis of HCV, pegylated-interferon alpha 2a 180 mcg (1x1 / week sc) was started in nine patients without spontaneous improvement and treatment was performed for six months. Treatment response was 100% at 6-month and 2-year follow-ups.
 Conclusion: Acute viral hepatitis C is a disease that should not be overlooked.
 After diagnosis, 8-12 weeks should be waited for spontaneous viral clearance. Patients who do not develop spontaneous viral clearance after 8-12 weeks can be largely treated with interferon alfa 2a therapy.
 Spontaneous recovery was observed in three of our patients after 8-12 weeks of follow-up (HCV-RNA was negative by PCR, AST-ALT values were normal).

Loss of Dnmt3a increases self-renewal and resistance to pegIFN-α in JAK2-V617F–positive myeloproliferative neoplasms

AbstractPegylated interferon alfa (pegIFN-α) can induce molecular remissions in patients with JAK2-V617F–positive myeloproliferative neoplasms (MPNs) by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as DNMT3A, have been reported to have poorer responses to pegIFN-α. We investigated whether DNMT3A loss leads to alterations in JAK2-V617F LT-HSC functions conferring resistance to pegIFN-α treatment in a mouse model of MPN and in hematopoietic progenitors from patients with MPN. Long-term treatment with pegIFN-α normalized blood parameters and reduced splenomegaly and JAK2-V617F chimerism in single-mutant JAK2-V617F (VF) mice. However, pegIFN-α in VF;Dnmt3aΔ/Δ (VF;DmΔ/Δ) mice worsened splenomegaly and failed to reduce JAK2-V617F chimerism. Furthermore, LT-HSCs from VF;DmΔ/Δ mice compared with VF were less prone to accumulate DNA damage and exit dormancy upon pegIFN-α treatment. RNA sequencing showed that IFN-α induced stronger upregulation of inflammatory pathways in LT-HSCs from VF;DmΔ/Δ than from VF mice, indicating that the resistance of VF;DmΔ/Δ LT-HSC was not due to failure in IFN-α signaling. Transplantations of bone marrow from pegIFN-α–treated VF;DmΔ/Δ mice gave rise to more aggressive disease in secondary and tertiary recipients. Liquid cultures of hematopoietic progenitors from patients with MPN with JAK2-V617F and DNMT3A mutation showed increased percentages of JAK2-V617F–positive colonies upon IFN-α exposure, whereas in patients with JAK2-V617F alone, the percentages of JAK2-V617F–positive colonies decreased or remained unchanged. PegIFN-α combined with 5-azacytidine only partially overcame resistance in VF;DmΔ/Δ mice. However, this combination strongly decreased the JAK2-mutant allele burden in mice carrying VF mutation only, showing potential to inflict substantial damage preferentially to the JAK2-mutant clone.

Diagnosis and treatment of viral hepatitisB andD in 2024

Despite the availability of vaccines, hepatitisB remains asignificant cause of fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The increase in reported hepatitisB cases in Germany is attributed to factors such as immigration and the hepatitisB surface antigen (HBsAg) screening introduced in 2020 as part of health check-ups. The indication for treatment depends on various factors, including the level of hepatitisB virus (HBV) DNA and inflammatory activity. Nucleos(t)ide analogues are the preferred treatment option, but functional cure, defined as HBsAg loss, is rare. In principle, treatment with nucleos(t)ide analogues should usually be discontinued after loss of HBsAg, but can be stopped earlier under certain conditions and is currently the subject of ongoing research. Pregnancy and immunosuppression in the context of hepatitisB require special attention. In addition, apossible hepatitisD virus co-infection must always be taken into account, which is why every HBsAg-positive person should be tested for anti-HDV. Since 2020, the entry inhibitor bulevirtide has become anew treatment option alongside pegylated interferon alfa, which represents asignificant advance in the treatment landscape.

A Phase 3b, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-Njft (P1101) in Adult Patients with Polycythemia Vera

Background and Significance: Polycythemia vera (PV), the most common chronic myeloproliferative neoplasm in the United States, is a long-term, debilitating, life-threatening cancer with limited treatment options. Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis. Cytoreductive therapy is recommended for high-risk and in some low-risk patients. Ropeginterferon alfa-2b-njft (P1101) is the first and only FDA-approved interferon for treating PV regardless of patients' risk category or past treatment history. The FDA-approved dosing for ropeginterferon alfa-2b-njft in patients with PV is a starting dose of 50 or 100 mcg every 2 weeks, with dose increases of 50 mcg every 2 weeks up to a maximum of 500 mcg. Clinical trial results confirmed high complete hematologic response (CHR) rates and molecular responses to ropeginterferon alfa-2b-njft, however, time to achieve CHR can take 6 months or longer because dose escalation to the highest maintenance dose ranged from 16 to 28 weeks. It is expected that the faster and simpler dosing scheme of 250-350-500 mcg, escalated every 2 weeks may allow patients to achieve complete hematologic responses significantly earlier with acceptable tolerability and safety. This notion was supported in a recently reported clinical study (Jin et al. Exp Hematol Onc 2023). To further assess the 250-350-500 mcg dosing regimen, this Phase 3b, randomized, open-label, parallel group, multicenter study (NCT05481151) of U.S. and Canadian patients will evaluate the efficacy and safety of ropeginterferon alfa-2b-njft when using the above described dose-escalation scheme directly compared with the approved dosing scheme. Study Design and Methods: The planned enrollment for this study is approximately 100 patients with PV aged ≥18 years from the U.S. and Canada. Patients will be randomized (1:1) into either the approved dosing regimen arm or the amended dose-escalation scheme arm (Figure 1). Inclusion criteria include diagnosis of PV according to the WHO 2008 or 2016 criteria, hemoglobin ≥10 g/dL for females, and hemoglobin ≥11 g/dL for males at screening, neutrophil count ≥1.5 × 10 9/L at screening. Exclusion criteria include: any contraindications to interferon alfa or hypersensitivity to interferon alfa, having stopped prior interferon alfa therapy due to low efficacy or poor tolerability, severe or serious diseases or any other diseases that the investigator determines may affect the subject's participation in this study, or the use of any investigational drug <4 weeks prior to the first dose of ropeginterferon alfa-2b-njft. Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included. Patients in the approved dosing arm will undergo HU tapering by 25% for the first 2 weeks, followed by 50% for weeks 3-4, 75% for weeks 5-6, and discontinuing completely during week 7 and onwards. Patients in the amended dose-escalation scheme arm are required to discontinue HU immediately upon initiation of ropeginterferon alfa-2b-njft. The primary efficacy endpoint is CHR (defined as hematocrit <45% in the absence of phlebotomy in the previous 12 weeks, white blood cell count ≤10 × 10 9/L, and platelets ≤400 × 10 9/L) at Week 24. Secondary endpoints include time to CHR, proportion of patients in CHR at Weeks 8, 12, 16, 20, 24, 36, and 48; time to maintenance dose (stable dose for 3 consecutive doses); and time to freedom from phlebotomies. The core treatment period will be 24 weeks followed by a 24-week extension period and a 4-week safety follow-up. Ropeginterferon alfa-2b-njft (P1101) will be provided in single-use 500-mcg prefilled syringes for subcutaneous administration every 2 weeks. The approved dosing arm will initiate with a starting dose of 100 mcg (Day 0) and increase by 50-mcg every 2 weeks up to a maximum dose of 500 mcg. The amended dosing arm will initiate with a starting dose of 250 mcg (Day 0), increase to 350 mcg at Week 2, and increase to a maximum of 500 mcg at Week 4. Dose adjustments will be allowed if safety or tolerability concerns arise. Cochran-Mantal-Haenszel test stratified by investigator sites will be used for analyzing the primary efficacy endpoint at Week 24. General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.

Saliva As a Non-Invasive Source to Monitor JAK2 V617F variant Allele Frequency (VAF) in Myeloproliferative Neoplasm (MPN): Implications for Dissecting the Mechanism of Interferon Alfa (IFNα) Response and Identification of Predictors of Response

Myeloproliferative Neoplasm (MPN) is a group of chronic blood cancers characterized by the somatic acquisition of mutations, in particular Janus Activated Kinase 2 (JAK2V617F), which lead to constitutive activation of myeloid cytokine receptors. Interferon alfa (IFNα) is the only known therapy that induces a molecular response by decreasing the Variant Allele Frequency (VAF) of JAK2V617F (Mullally et al, Blood 2013; Mosca et al, Blood, 2021). However, not all MPN patients on IFNα enjoy a molecular response, and why some patients respond and others do not remains unclear. Our long-term goal is to identify early biomarkers that predict for a molecular response to IFNα by following in depth MPN patients who are beginning IFNα dosing for one year with daily sampling of leukocyte DNA to monitor day-to-day changes in the driver mutation VAF using digital PCR (dPCR) (Cordua et al, Blood, 2019). Biosample collection and processing: peripheral blood was drawn into an EDTA tube and aliquoted into 500 µL stocks. Saliva was collected via passive drool and Zymo DNA/RNA Shield was added in a 1:1 dilution. DNA purification: DNA was purified using the Zymo Research Quick-DNA Miniprep Plus Kit and DNA yields (ng/µL) were quantified using the Qubit Flurometer. dPCR: DNA was added to master mix, JAK2WT and JAK2V617F specific primers and fluorescent probes, and sterile water. dPCR protocol: 10-minute pre-heat at 96°C, followed by 45 cycles of denature at 96°C for 30 seconds/anneal-extend at 61°C for 60 seconds, analyzing for JAK2WT and JAK2V617F fluorescent signals to quantify the amount of DNA (cp/µL) per allele. VAF was calculated using the amounts of DNA (JAK2V617F)/(JAK2WT+JAK2V617F). First, using stored samples from patients received before and during IFNα treatment, we identified variable responses of the JAK2V617F VAF to IFNα. We observed that patients with a positive clinical response to IFNα had an increase in JAK2V617F VAF immediately after initiating this therapy, followed by an eventual decrease. Then, we showed the feasibility for a study using daily saliva sampling in an IRB-approved observational trial to monitor daily VAF trends via saliva sampling for one year. Participants provided daily sampling starting from ~1 month before initiating IFNα therapy. So far, we have recruited eight patients. For most patients, high DNA yields (> 5 ng/µL) can be consistently obtained (Additional Content A). For one patient (IFN01) with initial low yields, we were able to improve those yields with positive reinforcement (e.g., smelling lemon-scented stickers). Next, we view that most patients can maintain consistent daily sampling times and food/drink conditions. Using the daily sampling, we have developed JAK2V617F change curves in response to IFNα (Additional Content B). There is daily variation in VAFs (hypothesized to be from variable buccal epithelial contamination), however clear trends can be seen. One patient (IFN01) displays a steep increase in JAK2V617F VAF, another (IFN07) displays a more gradual increase, and two patients (IFN03, IFN04) display no noticeable change. These trends will be interesting for continued observation to determine if they will correlate with long-term outcome IFNα. From the above graphs, after viewing that weekly sampling (which for most patients are symbolized by the black circles for weekly IFNα injections) preserves the same VAF trends as daily sampling, we simulated 1000 weekly, bi-weekly and monthly data distributions by randomly selecting a data point from each consecutive time frame over the first 150-day period, respectively. We will then conduct a generalized linear model to construct a plot of predicted mean values across time and its 95% confidence intervals (CIs). We determined that moving forward, we can decrease the sampling frequency to weekly samples, since this will preserve fine detailed trends, as well as have the combination of ease for patient and frequent enough for patients to not forget sampling habits. Here, we explore the novel use of daily saliva for comprehensive and high resolution VAF tracking of MPN patients in a remote setting. We will continue to follow the day-to-day variation of VAF in response to IFNα and plan to expand the use of saliva to gene expression profiling. Overall, the results of this trial will be used to generate a preliminary model of IFNα response, which can be used to predict how likely a MPN patient will benefit from IFNα therapy.

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.

Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.

Moving toward disease modification in polycythemia vera

AbstractPolycythemia vera (PV) belongs to the BCR-ABL1–negative myeloproliferative neoplasms and is characterized by activating mutations in JAK2 and clinically presents with erythrocytosis, variable degrees of systemic and vasomotor symptoms, and an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia (AML). Treatment selection is based on a patient’s age and a history of thrombosis in patients with low-risk PV treated with therapeutic phlebotomy and aspirin alone, whereas cytoreductive therapy with either hydroxyurea or interferon alfa (IFN-α) is added for high-risk disease. However, other disease features such as significant disease-related symptoms and splenomegaly, concurrent thrombocytosis and leukocytosis, or intolerance of phlebotomy can constitute an indication for cytoreductive therapy in patients with otherwise low-risk disease. Additionally, recent studies demonstrating the safety and efficacy (ie, reduction in phlebotomy requirements and molecular responses) of ropegylated IFN-α2b support its use for patients with low-risk PV. Additionally, emerging data suggest that early treatment is associated with higher rates of molecular responses, which might eventually enable time-limited therapy. Nonetheless, longer follow-up is needed to assess whether molecular responses associate with clinically meaningful outcome measures such as thrombosis and progression to myelofibrosis or AML. In this article, we provide an overview of the current and evolving treatment landscape of PV and outline our vision for a patient-centered, phlebotomy-free, treatment approach using time-limited, disease-modifying treatment modalities early in the disease course, which could ultimately affect the natural history of the disease.

MPN-380 Interferon Alfa as a First- and Second-Line Treatment Option for Primary Myelofibrosis

MPN-380 Interferon Alfa as a First- and Second-Line Treatment Option for Primary Myelofibrosis

POSTER: MPN-380 Interferon Alfa as a First- and Second-Line Treatment Option for Primary Myelofibrosis

POSTER: MPN-380 Interferon Alfa as a First- and Second-Line Treatment Option for Primary Myelofibrosis

Cold autoimmune hemolytic anemia

Cold agglutinins are antibodies that recognize antigens on erythrocytes at temperatures below normal body temperature. Antibodies are of IgM nature and bind to “I” or “i” antigens on red blood cells, causing agglutination in red blood cells. This situation results in anemia by creating extravascular hemolysis. If there is no underlying disease, it is called primary or idiopathic cold agglutinin disease (CAD), and if there is, it is called secondary cold agglutinin syndrome (CAS). Primary CAD is an extremely rare disease, with an incidence and prevalence of 1 per million and 16 per million, respectively. It is seen twice more in women than in men, and the median age of diagnosis is 67 (between 30-92 years). The etiology of CAS includes infections, autoimmune and lymphoproliferative diseases. There are cold-related symptoms and symptoms of anemia in the clinic. In treatment, it is necessary to avoid cold in order to reduce cold-induced symptoms and hemolysis. Currently, the most effective treatment for reducing antibody production is rituximab. It can be given alone or in combination with bendamustine, interferon alfa, fludarabine and prednisolone. bortezomib is used when rituximab is ineffective or contraindicated. Plasmapheresis or intravenous immunoglobulin can be given when there is critical hemolysis or when the effectiveness of immunosuppressive therapy may start late. Treatment in CAS is the treatment of the underlying disease.

Hepatitis C Virus: Insights Into Its History, Treatment, Challenges, and Future Directions.

Hepatitis C virus (HCV) is a global public health concern with significant impacts. It primarily spreads through blood-to-blood contact, such as sharing needles among drug users. Given the wide prevalence of risk factors, HCV continues to pose a major threat. Hence, it is crucial to understand its characteristics, structure, and genotypes to prevent, treat, and potentially eradicate it. This narrative review aims to explore the history of HCV treatment, highlight the breakthroughs achieved with direct-acting antiviral(DAA) therapy, address potential barriers to HCV eradication, and discuss future treatment possibilities. For this article, relevant studies were identified using various databases, including PubMed, ClinicalTrials.gov, and Journal Storage. The literature search revealed that after identifying HCV and studying its characteristics, interferon alfa and ribavirin became primary treatment options. However, due to their limited coverage against different HCV genotypes, ethnic variations, and suboptimal sustained virological response, the development of DAAs became essential. Combining various DAAs, such as sofosbuvir and velpatasvir, for a duration of 12 weeks has become the standard HCV treatment, with effectiveness against most genotypes. Additionally, ongoing clinical trials have shown promising results for other drugs such as CDI31244/sofosbuvir/velpatasvir, sofosbuvir/coblopasvir, and daclatasvir/asunaprevir. Despite the success of DAAs and ongoing efforts to discover more effective treatments, the high costs of DAAs pose a significant challenge to eradicating HCV, as not all patients can afford these expensive therapies. Furthermore, the ability of HCV to mutate limits the potential for vaccine development. Therefore, it is crucial to focus on developing more cost-effective strategies to control the spread of HCV and create novel, highly effective, and affordable DAAs.

Atypical early presentation of subacute sclerosing panencephalitis in children: A case series

Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease of children and young adults that may occur as an uncommon complication 7–10 years after a measles infection. In measles – endemic countries like India, the incidence of this fatal disease is high and more number of new cases are detected in recent times. In this case series, we have presented three cases of SSPE between the 4 and 5 years age group, presented with abnormal movement and neuroregression and diagnosed by characteristic clinical features, raised anti-measles antibody titer in CSF, and typical Electroencephalography findings. All of them had a history of measles infection before the vaccination and very short latency period between measles infection and the development of SSPE. They were discharged in stable condition after the treatment with oral Isoprinosine and intrathecal Interferon alfa 2b. Early age of presentation, short latency period, and apparently good response to treatment for the time being prompted us to present these cases.

Key principles of drug therapy in patients with chronic myeloid leukemia

Objective: to summarize scientific information about the basic principles of modern drug therapy for patients with chronic myeloid leukemia (CML) considering their individual characteristics.Material and methods. The basis of the study included modern scientific articles and clinical guidelines on CML diagnosis and treatment (2021), State Register of Medicines (SRM) of the Russian Federation, instructions for the use of medicines. The following methods were used: structural analysis, analytical method, content analysis, retrospective analysis, systematic approach, situational-logical and graphical methods of analysis.Results. The analysis made it possible to summarize scientific information about the basic principles of drug therapy for patients suffering from CML. It was revealed that the problem of CML therapy today is relevant, since every year there is an increase in the incidence of this nosology. Currently, the most significant is the prescription of tyrosine kinase inhibitors (TKIs), since they have pronounced effects and are well tolerated by patients. Therapy for CML in TKIs prescription consists of several lines. Imatinib is the first line therapy because it has better safety profile. There are combinations with imatinib; for example, it is used together with interferon alfa, which allows, in some cases, to increase the response to treatment. The following drugs are used in the second line: nilotinib, dasatinib, bosutinib, ponatinib. If TKI therapy is ineffective, it is possible to prescribe standard chemotherapy, interferon therapy, or bone marrow transplantation in the absence of contraindications. Studies are underway on the possibility of using and including in clinical guidelines such drugs as arsenic trioxide, decitabine, omacetaxime, inhibitors of farnesyl transferases, granulocyte-macrophage factors, antitumor vaccines. The analysis of SRM identified 27 trade names for TKIs, the share of domestic drugs was 60%. There were no Russian analogues for bosutinib and ponatinib in SRM, which are recommended for use in case of ineffective TKI therapy of previous lines.Conclusion. The study of drug provision for CML patients is an urgent task for pharmaceutical practice and for the healthcare system as a whole. Currently, the acute issues are the individual approach to the treatment of each CML patient considering concomitant diseases, and the search for new, more effective drugs that can increase the life expectancy and quality of life of patients suffering from this disease.

Biologic therapies for psoriasis and eyes

Psoriasis is a systemic inflammatory disorder, manifested mainly by skin lesions, but the inflammation also may affect the joints and eye. Many comorbidities have been described in association with psoriasis, including metabolic syndrome and coronary plaques. The pathomechanism of psoriasis is multifaceted. Both genetic and immunologic aspects play a role in stimulating inflammation. Genetic susceptibility is conditioned by presence of the human leukocyte antigen-C*06:02 risk allele and the inflammatory reaction secondary to cytokines, such as tumor necrosis factor α, interleukin 17 (IL-17), IL-20, IL-23, and interferon alfa. Besides the conventional therapy of topical steroids and immunosuppressants, biologic therapies are widely used in the treatment of psoriasis, psoriatic arthritis, and coexisting uveitis. In the majority of cases, biologic therapy has a beneficial effect on uveitis, but in some cases, some of these drugs can lead to serious side effects threatening vision.

Association of Alanine Aminotransferase Flares to Hepatitis B Surface Decline During Tenofovir Alone or With Pegylated Interferon Alfa.

We aimed to determine whether the intensity of alanine aminotransferase (ALT) flares during antiviral therapy is associated with the level of hepatitis B surface antigen (HBsAg) decline. Quantitative HBsAg was determined during tenofovir monotherapy or tenofovir plus peginterferon alfa-2a in 201 participants with hepatitis B e antigen-positive or -negative chronic hepatitis B. A multivariable analysis identified factors associated with a shorter time to reduction in HBsAg. Fifty flares occurred during treatment of which 74% were moderate (ALT >5-10 × upper limit of normal) or severe (ALT >10 × upper limit of normal). These flares were associated with greater HBsAg decline compared with no flares. Significantly faster times to HBsAg decline >1 log 10 IU ( P = 0.04) and to HBsAg level <100 IU/mL ( P = 0.01) were observed with severe flares. Flare severity is a potentially important factor associated with shorter time to HBsAg reduction. These findings can be useful when evaluating HBsAg response to evolving hepatitis B virus therapies.