Peginterferon alfa-2a 180micrograms/0.5ml solution for injection pre-filled disposable devices

BackgroundMultiple sclerosis is an immune-mediated inflammatory disease, causing long-term disability in young adults. Most cases begin as relapsing-remitting multiple sclerosis. Some people have a form of relapsing-remitting multiple sclerosis known as highly active relapsing-remitting multiple sclerosis, defined as multiple sclerosis with unchanged or increased disease activity despite prior treatment with at least one disease-modifying therapy.ObjectivesTo appraise the clinical and cost-effectiveness of natalizumab [Tysabri® (Biogen, Cambridge, MA, USA)] and natalizumab biosimilar [Tyruko® (Sandoz)] for treating highly active relapsing-remitting multiple sclerosis compared to other disease-modifying therapy.DesignSystematic review with network meta-analysis and economic model. Searches last updated in April 2024.ResultsWe included 42 studies (22,409 participants): 40 in people with relapsing-remitting multiple sclerosis and 2 in highly active relapsing-remitting multiple sclerosis. Six studies also reported data separately for highly active relapsing-remitting multiple sclerosis. Only four studies evaluated natalizumab or natalizumab biosimilar; none provided data on those with highly active relapsing-remitting multiple sclerosis. Follow-up ranged from 4 to 36 (median 24) months. Most interventions reduced relapses (39 studies, 17 interventions) and magnetic resonance imaging lesions (19 studies, 11 interventions for gadolinium enhancing lesions and 17 studies, 12 interventions for T2-weighted lesions) compared to placebo. Alemtuzumab, ocrelizumab, cladribine, natalizumab, fingolimod and peginterferon beta-1a reduced disease progression compared to placebo (15 studies, 12 interventions). There were no differences in any adverse events (24 studies, 16 interventions), serious adverse events (31 studies, 15 interventions) or treatment-related adverse events (8 studies, no network meta-analysis) for any intervention compared to placebo. Fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b and peginterferon beta-1a were associated with an increased treatment discontinuation (29 studies, 13 interventions). There was little evidence for a difference in quality of life. There was no evidence of a difference between natalizumab and natalizumab biosimilar for relapse rates [rate ratio 0.65 (95% credible interval 0.33 to 1.23], gadolinium enhancing lesions [hazard ratio 1.29 (0.69 to 2.37)], T2-weighted lesions [hazard ratio 1.07 (0.73 to 1.57)], any adverse events [hazard ratio 1.06 (0.77 to 1.46)] or treatment discontinuation [hazard ratio 0.48 (0.13 to 1.76)]. Data in highly active relapsing-remitting multiple sclerosis were available for fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, autologous haematopoietic stem cell treatment and placebo. We also included one study on natalizumab conducted in a population that was close to our definition of highly active relapsing-remitting multiple sclerosis. All interventions except interferon beta-1a were associated with reduced relapse risk compared to placebo (six studies; seven interventions). Compared with natalizumab-intravenous, natalizumab biosimilar-intravenous and natalizumab subcutaneous, all treatments had greater net benefit at £20,000-30,000/quality-adjusted life-year, with the only exception being ocrelizumab, which had lower net benefits. Costs were generally higher on natalizumab than other treatments, though there was no difference in quality-adjusted life-years with 95% credible interval completely overlapping. The results and conclusions were unchanged under all sensitivities. VOI analysis found that the greatest contributor to decision uncertainty was the effectiveness of treatments.ConclusionsThere is no direct evidence on the effectiveness of natalizumab or its biosimilar in patients with highly active relapsing-remitting multiple sclerosis. Limited data suggest similar effectiveness in patients with relapsing-remitting multiple sclerosis. The economic model found that natalizumab and natalizumab biosimilar were not cost-effective compared to any of the included comparators in highly active relapsing-remitting multiple sclerosis, with similar quality-adjusted life-years but higher costs, with the only exception being ocrelizumab.Future workThere is need for studies of natalizumab and natalizumab biosimilar in people with highly active relapsing-remitting multiple sclerosis.Study registrationThe study is registered as PROSPERO CRD42024556838.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR165943) and is published in full in Health Technology Assessment; Vol. 30, No. 60. See the NIHR Funding and Awards website for further award information.

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Ropeginterferon alfa-2b is an interferon used in the treatment of myeloproliferative neoplasms, particularly polycythemia vera. Its efficacy in achieving hematologic and molecular responses has been demonstrated in clinical trials, but pooled data on long-term outcomes and sustained response remain limited. This systematic review and meta-analysis aimed to evaluate the hematologic and molecular response over 36 months. PubMed, Scopus, Science Direct, and Google Scholar databases were searched to identify studies reporting hematologic and molecular responses to ropeginterferon alfa-2b. Studies were included if they provided data on complete hematologic response (CHR) and JAK2V617F variant allele frequency (VAF) reduction. Pooled proportions and mean reductions were calculated using random-effects models. The pooled proportion of CHR increased progressively from 0.19 (95% CI: 0.04-0.57) at 3 months to 0.73 (95% CI: 0.17-0.97) at 36 months. Molecular response, measured by VAF reduction, deepened over time from - 7.33 (95% CI: -9.85 to -4.81) at 3 months to -54.90 (95% CI: -65.61 to -43.99) at 36 months. Subgroup analyses revealed significant variability in response rates, particularly in early follow-up periods. Ropeginterferon alfa-2b achieves significant and sustained hematologic and molecular responses over 36 months. This makes it a promising treatment for polycythemia vera. While variability in early responses needs further investigation, the sustained long-term efficacy compared to hydroxyurea supports its use in clinical practice. Future studies should focus on identifying predictors of response and optimizing treatment protocols to maximize patient outcomes.

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BackgroundRopeginterferon alfa-2b, a novel monopegylated interferon with improved pharmacokinetics, has emerged as a promising cytoreductive agent for managing polycythemia vera (PV). Despite increasing adoption, evidence synthesis of its efficacy and safety compared to standard care remains limited. The manuscript aimed to evaluate the efficacy of ropeginterferon alfa-2b in comparison to standard treatment options, including hydroxyurea and phlebotomy, in achieving complete hematologic response, partial molecular response (PMR), and reducing JAK2V617F allele burden in patients with PV.MethodsA systematic search of 4 databases was conducted up to April 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing ropeginterferon alfa-2b with standard therapies in PV patients were included. Meta-analyses were performed using random-effects models to derive odds ratios for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Sensitivity and subgroup analyses were conducted, and risk of bias was assessed using RoB 2.0.ResultsThree RCTs comprising 522 patients were analyzed. Ropeginterferon alfa-2b showed no statistically significant advantage overall or over hydroxyurea for complete hematological response (CHR), PMR, or JAK2 allele burden reduction. However, subgroup analyses revealed significant benefits over phlebotomy alone in all 3 outcomes: CHR (odds ratio [OR] 3.05; 95% confidence interval [CI]: 1.36-6.80; P = .007), PMR (OR 36.34; 95% CI: 2.11-625.93; P = .01), and allele burden reduction (MD -13.70; 95% CI: -19.24 to -8.16; P ConclusionRopeginterferon alfa-2b demonstrates no statistically significant difference compared to hydroxyurea, but gives better outcomes over phlebotomy in short-term efficacy for PV management. Its favorable molecular and hematologic outcomes support its role as a disease-modifying therapy, particularly in low-risk patients. However, larger and longer-term trials are needed to confirm these benefits across broader populations.

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BackgroundChronic hepatitis D virus (HDV) continues to be a global health concern, and the infection remains challenging to treat. Over the past few decades, pegylated interferons, typically in combination with therapy for hepatitis B, have become the standard of care, with considerable side effects and frequently unsatisfactory results. Several new therapies are emerging, including bulevirtide and lonafarnib. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of bulevirtide, interferons, and nucleos(t)ide analogs, alone or in combination, for the treatment of chronic hepatitis D.MethodsPubMed, Embase, and Cochrane databases were searched for randomized controlled trials and nonrandomized interventional studies assessing HDV RNA suppression, biochemical response, combined response, and histological improvement with various therapies. NMA was performed using a frequentist random-effects model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and forest plots were generated.ResultsThirteen studies (n = 922) were included, studying nine possible treatment arms. At the end of treatment, 31.8% achieved a virological response. Bulevirtide monotherapy (OR 38.63, p p p p n = 183) was not statistically significant with any intervention compared with control.ConclusionBulevirtide and peginterferon alpha combination therapy may offer the most promising treatment for chronic hepatitis D. More studies are needed to assess the efficacy of this regimen and establish the optimum dose and duration of treatment.

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Aim: Polycythemia vera (PV), a rare, chronic myeloproliferative neoplasm, that negatively impacts patient outcomes, and optimal therapy remains unclear due to a lack of head-to-head trials. A targeted literature review and feasibility assessment for an indirect comparison of ropeginterferon alfa-2b-njft versus peginterferon alfa-2a or ruxolitinib, using standard of care comprising hydroxyurea (HU) as a common comparator was conducted. Materials & methods: A targeted literature review evaluated clinical comparative evidence for PV treatments published between January 2014 and May 2024 in PubMed and relevant conference abstracts. End points of interest included complete hematologic response, molecular response, allele burden, event-free survival and safety. The feasibility of a network metaanalysis (NMA) was evaluated based on homogeneity of patient populations, treatment regimens and end point definitions. Results: Of 193 PubMed records and 460 conference abstracts screened, 40 records were included, representing evidence from 11 randomized controlled trials and 10 observational studies. Among these, 20 studies formed connected evidence networks for the end points of interest. Substantial heterogeneity across studies precluded a robust NMA: patient populations varied (newly diagnosed, highrisk, low-risk, HU-refractory or -intolerant), complete hematologic response definitions differed (e.g., requirement for absence of disease-related symptoms), molecular response thresholds were inconsistent, follow-up durations varied and definitions of standard of care ranged from almost exclusive use of HU to mixed regimens. Conclusion: An NMA for PV treatments was not feasible due to significant clinical and methodological heterogeneity across studies, including differences in patient characteristics, treatments, outcome definitions and follow-up times. These findings highlight the importance of standardized clinical trial designs and outcome definitions to enable robust comparative evidence generation for rare conditions like PV.

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