BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Although UST has demonstrated good efficacy and safety in CD, long-term real-world...BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Although UST has demonstrated good efficacy and safety in CD, long-term real-world data in Chinese patients are relatively scarce. METHODS: A single-center, observational retrospective study was conducted in the First Affiliated Hospital of Anhui Medical University. Comprehensive baseline demographic characteristics, clinical parameters, potential predictors of clinical remission of CD patients treated with UST from January 2020 to January 2024 were collected and analyzed. RESULTS: A total of 348 CD patients were included. At week 52, the clinical remission rate was 70.95%, endoscopic remission 24.68%, C-Reactive Protein (CRP) normalization 54.11%, and fecal calprotectin (FCP) normalization 48.57%. Prior biologic exposure, CRP reduction at week 8, and baseline hemoglobin level were independent predictors of clinical remission. The mean survival duration with UST was 172 weeks (SE = 6, 95% CI: 160-185). CONCLUSIONS: This study demonstrated favorable effectiveness, persistence, and safety of UST in CD patients. Prior biologic exposure, early CRP reduction and hemoglobin level were associated with clinical remission at 52 weeks.
INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality globally. For years, systemic treatment options were limited to tyrosine kinase inhibitors with modest outcomes. The introduction o...INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality globally. For years, systemic treatment options were limited to tyrosine kinase inhibitors with modest outcomes. The introduction of immunotherapy has transformed the treatment paradigm, establishing immunotherapy as first-line treatment for advanced disease. Among these, tremelimumab -an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody- is a key therapeutic agent in the evolving management of HCC. AREAS COVERED: This review offers a detailed examination of the pharmacological characteristics of tremelimumab and synthesizes evidence from clinical trials assessing its efficacy and safety as both monotherapy and in combination for HCC. It also explores ongoing studies and future perspectives on the role of tremelimumab across diverse stages in the management of HCC. EXPERT OPINION: Tremelimumab has reshaped the treatment of HCC through its use as a single high-dose priming agent in combination with durvalumab. This approach effectively triggers durable immune responses with a favorable safety profile. Ongoing studies are evaluating its potential in earlier and intermediate stages of HCC, particularly as part of neoadjuvant and conversion therapy strategies. However, the lack of predictive biomarkers specific to tremelimumab remains a key limitation. Future research should focus on identifying patients most likely to benefit from tremelimumab-based combinations.
BACKGROUND: Following the approval of intravenous (IV) infliximab (IFX) in the 1990s, Celltrion developed the first monoclonal antibody biosimilar for IV IFX (Remsima®: Celltrion, South Korea), followed by the first and...BACKGROUND: Following the approval of intravenous (IV) infliximab (IFX) in the 1990s, Celltrion developed the first monoclonal antibody biosimilar for IV IFX (Remsima®: Celltrion, South Korea), followed by the first and only subcutaneous IFX, (Remsima® SC). A liquid formulation of IV IFX has been developed that eliminates the need for reconstitution and introduces a 350 mg vial size not previously available with the powder formulation. This study evaluated the operational benefits and cost savings of the liquid formulation of IV IFX compared to the powder formulation, from the perspective of healthcare professionals across seven European countries. RESEARCH DESIGN AND METHODS: Semi-structured interviews were conducted with 21 hospital pharmacists and nurses involved in IV IFX preparation from May to June 2025. RESULTS: Interviewees noted that eliminating reconstitution reduced preparation time by 51% and resource costs by 20% per patient episode compared to the powder formulation, significantly alleviating healthcare professionals' workload. CONCLUSIONS: The liquid formulation of IV IFX streamlines preparation, enhances operational efficiency, and reduces costs compared to the powder formulation. These savings allow resource reallocation to patient care, improving cost-effectiveness of IV IFX therapy. Its adoption is expected to optimize healthcare delivery across European healthcare systems.
OBJECTIVES: Uveitis is a prevalent complication of juvenile idiopathic arthritis (JIA), leading to ocular morbidity. This study aimed to evaluate uveitis frequency in JIA patients on biologics and explore the impact of b...OBJECTIVES: Uveitis is a prevalent complication of juvenile idiopathic arthritis (JIA), leading to ocular morbidity. This study aimed to evaluate uveitis frequency in JIA patients on biologics and explore the impact of biologic selection on its occurrence. METHODS: Among 2,385 JIA patients reviewed, 101 patients who developed uveitis were analyzed. This patients were categorized based on their uveitis development: under methotrexate, after discontinuation of methotrexate, and under biologics. RESULTS: Uveitis frequency among all reviewed JIA patients was 6.3%. Among those who developed uveitis while receiving biologics, 30 were on etanercept and one on infliximab at the time of onset. When the entire cohort of JIA patients treated with biologics for joint symptoms was evaluated, it was observed that out of 365 patients using etanercept, uveitis developed in 30 individuals, in one out of 39 patients using infliximab, while no cases of uveitis were observed among 285 patients using adalimumab. CONCLUSION: In this study we observed a larger frequency of new onset uveitis in JIA patients treated with TNF receptor fusion proteins than those treated with anti-TNF monoclonal antibodies. Monoclonal anti-TNF-α agents may remain the preferred options. This study highlights the necessity of integrating uveitis risk assessment into JIA treatment strategies.
BACKGROUND: For moderate-to-severe psoriasis, clinical guidelines recommend biologic treatments after failure of at least one traditional systemic therapy. Biologics target different pathways, but a common challenge is l...BACKGROUND: For moderate-to-severe psoriasis, clinical guidelines recommend biologic treatments after failure of at least one traditional systemic therapy. Biologics target different pathways, but a common challenge is loss of efficacy, often requiring a switch. This study explores real-world therapeutic management of moderate-to-severe psoriasis, focusing on biologic treatments. METHODS: A retrospective study was conducted using health records of adult patients currently receiving biologics at Sant'Orsola Hospital in Bologna. Therapeutic sequences were investigated using state sequence analysis. Within-sequence Shannon entropy was calculated and used as the outcome in linear regression models. A directed acyclic graph informed the hierarchical regression models to identify factors influencing treatment duration. RESULTS: The cohort included 364 patients. Adalimumab was the most common first-line biologic (27%), followed by secukinumab (18%) and etanercept (16%). Nearly half of patients (48%) switched treatments. Increasing age was associated with lower sequence heterogeneity (β = -0.001, = 0.002). Ustekinumab demonstrated the longest median treatment duration (1,841 days), while etanercept had the shortest (639 days). After adjusting for confounding variables, ustekinumab maintained its positive effect on treatment duration (β = 0.285, = 0.009). CONCLUSION: The treatment duration for ustekinumab was encouraging, supporting its potential role as a durable option in these patients.
INTRODUCTION: Osteoporosis is a significant public health issue due to its associated morbidity, mortality, and economic burden. Despite available effective treatments, a treatment gap persists, characterized by delayed...INTRODUCTION: Osteoporosis is a significant public health issue due to its associated morbidity, mortality, and economic burden. Despite available effective treatments, a treatment gap persists, characterized by delayed diagnosis, undertreatment, and poor adherence. Biosimilars, such as biosimilars for denosumab, offer an opportunity to improve treatment accessibility and affordability for osteoporosis and cancer-related bone loss. AREAS COVERED: This review explores the current treatment challenges in osteoporosis, the potential of denosumab biosimilars in improving access and outcomes, and the necessity of a multidisciplinary, patient-centered approach. EXPERT OPINION: The emergence of biosimilars for denosumab offers an opportunity to enhance accessibility and affordability of osteoporosis treatment, as biosimilars provide effective and economic versions of reference biologic therapies. A multidisciplinary approach is vital in managing osteoporosis, central to which is the patient, whose preferences, values, and lifestyle must guide the treatment plan. Healthcare providers play a crucial role in educating patients, promoting adherence to prescribed treatments, and involving patients in their own care to improve health outcomes.
Szepietowski JC, Reich A, Feldman SR
… +12 more, Pulka G, Mekokishvili L, Tsiskarishvili N, Svarca I, Poder A, Singh G, Deodhar S, Kumar K, Marwah A, Loganathan S, Athalye SN, Wolff-Holz E
BACKGROUND: STELLAR-2 assessed the equivalent efficacy of the ustekinumab biosimilar, Bmab 1200, versus reference ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Safety, immunogenicity, and phar...BACKGROUND: STELLAR-2 assessed the equivalent efficacy of the ustekinumab biosimilar, Bmab 1200, versus reference ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Safety, immunogenicity, and pharmacokinetics (PK) were also evaluated. RESEARCH DESIGN AND METHODS: In this double-blind, parallel-group, Phase 3 study, patients were randomized 1:1 to Bmab 1200 or reference ustekinumab in Treatment Period (TP)1, and at Week 16, those who responded to reference ustekinumab (improvement in Psoriasis Area and Severity Index [PASI] score ≥ 50%) were re-randomized (1:1) to continue reference ustekinumab or switch to Bmab 1200 in TP2. The primary endpoint was the change in PASI from baseline to Week 12. Equivalent efficacy was established if 90% and 95% confidence intervals (CIs) for the treatment difference were within predefined equivalence margins of ± 10% and ± 13%, respectively. RESULTS: Overall, 384 patients were randomized (Bmab 1200: = 191; reference ustekinumab: = 193) in TP1. At Week 12, the least squares mean treatment difference (0.6800%; 90% CI: -1.27, 2.63; 95% CI: -1.64, 3.00) was within the predefined equivalence margins for 90% and 95% CIs. Safety, immunogenicity, and PK were comparable between treatment groups. CONCLUSIONS: Bmab 1200 and reference ustekinumab had similar efficacy, safety, immunogenicity, and PK in patients with moderate-to-severe plaque psoriasis. TRIAL REGISTRATION: www.clinicaltrialsregister.eu identifier is 2021-006668-25; www.clinicaltrials.gov identifier is NCT05335356.
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing-remitting colonic inflammation. Despite advances in understanding UC pathogenesis, a definitive cure remains elus...INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing-remitting colonic inflammation. Despite advances in understanding UC pathogenesis, a definitive cure remains elusive. Current therapies aim to promote symptom resolution, mucosal healing, and ideally histologic remission. Moderate-to-severe UC patients may require advanced therapies, including biologics and small molecules, targeting pathways that have been implicated in the UC pathogenesis. AREAS COVERED: This review provides an in-depth analysis of current and emerging therapies targeting the interleukin (IL)-23 pathway in moderate-to-severe UC. It discusses both ustekinumab, a nonselective IL-12/23p40 blocker, and selective IL-23p19 inhibitors (i.e. mirikizumab, guselkumab, and risankizumab), covering their mechanisms of action, clinical efficacy, and safety profiles from registrative and post-marketing studies. The review also explores promising oral therapies under investigation, including IL-23 receptor (IL-23 R) antagonists and TYK2 inhibitors, highlighting their early-phase results. EXPERT OPINION: IL-23p19 inhibitors have shown significant efficacy in inducing and maintaining remission in UC, with favorable safety profiles. Oral agents represent an exciting frontier, potentially improving patient adherence and accessibility. Direct comparative trials are needed to refine therapeutic positioning in personalized treatment algorithms.
BACKGROUND: To demonstrate comparative efficacy of AVT03, a proposed denosumab biosimilar, versus reference product (RP) in postmenopausal women with osteoporosis. RESEARCH DESIGN AND METHODS: Participants received AVT03...BACKGROUND: To demonstrate comparative efficacy of AVT03, a proposed denosumab biosimilar, versus reference product (RP) in postmenopausal women with osteoporosis. RESEARCH DESIGN AND METHODS: Participants received AVT03 or RP; 60 mg subcutaneous on Day 1 and Month 6. At Month 12, AVT03 group received 3 dose while RP group received either a 3 dose of RP or a dose of AVT03. Primary endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) at 12 months and area under the effect curve (AUEC) of percent change from baseline (%Cfb) in serum C-terminal telopeptide of type I collagen (sCTX-1). Safety and immunogenicity were evaluated. RESULTS: The 95% confidence interval (CI)s of the least squares means difference between treatments for percent change from baseline in lumbar spine BMD to Month 12 (-0.58, 0.82) were entirely contained within the prespecified margin (-1.45%, 1.45%), supporting demonstration of comparative efficacy. The 95% CIs of the geometric mean ratio between treatments for AUEC of %Cfb sCTX-1 (0.97, 1.03) were entirely contained within the prespecified margin (0.80, 1.25), supporting demonstration of pharmacodynamic similarity. Safety and immunogenicity profiles were comparable throughout. CONCLUSION: Data supported demonstration of comparative efficacy between AVT03 and RP denosumab. Safety and immunogenicity profiles were similar. TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05395091.
INTRODUCTION: The successful clinical trials of the type I interferon (IFN) receptor monoclonal antibody, anifrolumab, have proven the benefit of IFN blockade in systemic lupus erythematosus (SLE), and paved the way for...INTRODUCTION: The successful clinical trials of the type I interferon (IFN) receptor monoclonal antibody, anifrolumab, have proven the benefit of IFN blockade in systemic lupus erythematosus (SLE), and paved the way for novel therapies targeting this pathway. AREAS COVERED: This review will cover the updated evidence regarding the efficacy and safety of anifrolumab since its positive phase III trial in 2020. In addition, indications of the clinical benefit of emerging IFN-targeting therapies, such as monoclonal antibodies targeting IFN-producing cells and small-molecule inhibitors of IFN signaling, currently in phase II/III clinical trials will be discussed. EXPERT OPINION: Evidence from clinical trials and real-world studies have revealed the potential for IFN blockade to reduce disease activity and flares, improve glucocorticoid (GC) tapering and increase the attainment of treat-to-target goals in SLE, including in refractory patients. The efficacy of IFN blockade across different SLE disease manifestations and patient subgroups remains under investigation, as well as the ability of such treatments to reduce end organ damage. Regardless, it is clear that IFN blockade has earned a place as part of the standard of care in SLE. Future studies are needed to define whether IFN blockade moves toward being a first-line treatment.
INTRODUCTION: This review aims to summarize real-world evidence on the use of biologic therapies in juvenile idiopathic arthritis (JIA), including systemic and non-systemic subtypes, and to explore treatment strategies....INTRODUCTION: This review aims to summarize real-world evidence on the use of biologic therapies in juvenile idiopathic arthritis (JIA), including systemic and non-systemic subtypes, and to explore treatment strategies. AREAS COVERED: The evolving therapeutic landscape of JIA, emphasizing the differential efficacy and safety profiles of biologic agents such as IL-1 and IL-6 inhibitors, TNF inhibitors, secukinumab and abatacept across JIA subtypes. Special attention is given to real-world registry data, observational studies, and cohort analyses evaluating treatment responses, disease remission rates, flare risk after biologic discontinuation, and the effectiveness of biosimilars. Evidence regarding biologic switching strategies and the challenges of treating difficult-to-manage subtypes such as systemic JIA and enthesitis-related arthritis are also addressed. EXPERT OPINION: Earlier use of biologic agents may become more widely accepted, particularly in high-risk JIA subtypes. This shift has the potential to promote earlier remission, reduce long-term joint damage and corticosteroid dependency, and minimize hospitalization and complications. However, this approach must be carefully balanced against increased treatment costs and potential long-term dependence on biologics.
INTRODUCTION: Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis and asthma. Sublingual immunotherapy (SLIT) is commonly used in clinical practice. Although its effectiveness has b...INTRODUCTION: Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis and asthma. Sublingual immunotherapy (SLIT) is commonly used in clinical practice. Although its effectiveness has been proven in randomized controlled trials and real-world studies, poor or no responses may occur in some cases. AREAS COVERED: The present review aims to summarize the main possible factors involved in ineffective SLIT treatment, including immunological mechanisms, molecular and diagnostic errors, non-purified extracts, inadequate dosage, and patients' intrinsic and extrinsic characteristics. Possible remedies are also reported to predict and overcome poor patient response to guarantee optimal treatment efficacy. EXPERT OPINION: Identifying the reason for SLIT ineffectiveness is clinically relevant. Allergologists should carefully investigate the possible cause of poor or no response to SLIT. Identification is important as the potential removal of the interfering problems might allow SLIT to continue. The most common causes of poor SLIT efficacy include diagnostic errors, incorrect allergen dosage and schedule, poor quality extract, comorbidity, impaired immune system function, and inadequate adherence.
INTRODUCTION: Inherited epidermolysis bullosa (EB) is a family of rare-inherited dermatoses that result in mucocutaneous fragility and blister formation inducible by minor trauma. Clinically, EB mainly presents as increa...INTRODUCTION: Inherited epidermolysis bullosa (EB) is a family of rare-inherited dermatoses that result in mucocutaneous fragility and blister formation inducible by minor trauma. Clinically, EB mainly presents as increased skin fragility with trauma-induced blisters and erosions, combined with extracutaneous manifestations and their complications in other epithelialized organs. No cure for inherited EB is currently available. Treatment of inherited EB is mainly supportive, aiming to reduce patients' pain and itching. AREAS COVERED: Some advances in the treatment of inherited epidermolysis bullosa have recently been achieved, including topical drug treatment, systemic drug treatment, gene-based therapy, and cell-based therapy. This review focuses on the treatment progress of inherited epidermolysis bullosa. PubMed was searched up to February 2025 to identify relevant studies on inherited EB. EXPERT OPINION: Emerging advances of therapies in gene-based therapy and cell-based therapy can partially address the symptoms of EB and provide hope for the patients.
INTRODUCTION: Until recently, the biological treatment options for hidradenitis suppurativa (HS) were largely restricted to adalimumab and secukinumab. In 2024, bimekizumab, an IL-17A and IL-17F antibody was introduced t...INTRODUCTION: Until recently, the biological treatment options for hidradenitis suppurativa (HS) were largely restricted to adalimumab and secukinumab. In 2024, bimekizumab, an IL-17A and IL-17F antibody was introduced to the clinical practice. AREAS COVERED: Bimekizumab offers a new therapeutic approach for managing HS. It was approved by the U.S Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2024. The available biologic therapies in HS treatment are described. The data from phase II and phase III clinical trials were analyzed to evaluate the bimekizumab effectiveness in HS treatment. Data from those trials and latest summaries of product characteristics (SmPC) were retrieved to investigate its safety profile. The current preliminary data regarding its long-term effectiveness from BE HEARD EXT (NCT04901195) trial were presented. EXPERT OPINION: The common side effects of bimekizumab were upper respiratory infections, candida infections and eczematous reactions across all indications. The favorable side effects profile and strong clinical effectiveness proved in clinical trials gave the bimekizumab potential to become the first-choice drug in HS treatment.
INTRODUCTION: Psoriasis is a chronic, systemic inflammatory disease with significant physical and psychosocial burden. Advances in understanding the pathogenesis of psoriasis, particularly the role of interleukin (IL)23/...INTRODUCTION: Psoriasis is a chronic, systemic inflammatory disease with significant physical and psychosocial burden. Advances in understanding the pathogenesis of psoriasis, particularly the role of interleukin (IL)23/Th17 axis, have led to the development of selective drugs targeting these cytokines. Among these, IL23 inhibitors (guselkumab, risankizumab, and tildrakizumab), represent the most recent class of biologic drugs approved for the management of moderate-to-severe plaque psoriasis. Since their approval, real-life data on the use of anti-IL23 have confirmed their high efficacy, durability, and favorable safety profile. AREAS COVERED: This narrative review summarizes real-world data on the effectiveness, also in difficult-to-treat areas, safety, and drug survival of IL23 inhibitors in psoriasis. EXPERT OPINION: Real-world evidence consistently confirms the strong efficacy, favorable safety profile, and long-term treatment durability of IL23 inhibitors across various patient subgroups, including those with comorbidities, prior biologic failures, and the involvement of difficult-to-treat areas. IL23 inhibitors have become key components of the therapeutic arsenal in psoriasis, and their performance in real-world settings continues to support their widespread adoption in clinical practice.
INTRODUCTION: Despite recent treatment breakthroughs, non-small cell lung cancer (NSCLC) remains the highest cause of cancer-related mortality. New therapies are urgently needed, particularly in patients without actionab...INTRODUCTION: Despite recent treatment breakthroughs, non-small cell lung cancer (NSCLC) remains the highest cause of cancer-related mortality. New therapies are urgently needed, particularly in patients without actionable genomic alterations (AGAs), who currently receive a combination of chemotherapy and anti-PD1/PD-L1 therapy. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate combining an antibody against Trop-2 and an exatecan payload which has shown activity in both breast cancer and NSCLC. With several drugs in this class, it is important to understand their activity and limitations in different subtypes of NSCLC. AREAS COVERED: The literature was reviewed for trials demonstrating activity of their preliminary and/or final results, Dato-DXd, was studied across multiple clinical trials, including the Phase 1 TROPION-PanTumor01 and Phase 3 TROPION-Lung01 studies that are deemed pivotal in demonstrating its efficacy across different patients. EXPERT OPINION: Dato-DXd is a promising new option for NSCLC treatment with clear evidence of activity, shown early signals of efficacy, particularly in non-squamous NSCLC and patients with AGAs. However, patient selection remains paramount for future clinical development. Further research is necessary to optimize dosing strategies, manage adverse events, and better understand its role in both frontline and relapsed/refractory treatment settings as part of combination therapy, as well as neoadjuvant therapy prior to surgery.
BACKGROUND: This study compared efficacy, pharmacokinetics (PK), immunogenicity, and safety between AVT06, proposed biosimilar to reference product (RP) aflibercept (Eylea®), in participants with neovascular age-related...BACKGROUND: This study compared efficacy, pharmacokinetics (PK), immunogenicity, and safety between AVT06, proposed biosimilar to reference product (RP) aflibercept (Eylea®), in participants with neovascular age-related macular degeneration (nAMD). METHODS: In this randomized, double-masked, multicenter, active-controlled trial, treatment naïve participants received intravitreal injections of AVT06 or RP (2 mg) over 48 weeks. The primary endpoint was the change from baseline to Week 8 in best-corrected visual acuity (BCVA). Secondary endpoints included BCVA improvements and changes in Central Subfield Thickness (CST). PK, immunogenicity, and safety were also assessed. RESULTS: The 90% and 95% confidence intervals (-0.60, 2.14 and -0.86, 2.40, respectively) in least squares mean difference in BCVA letter score from baseline to Week 8 were contained within the pre-specified equivalence margin of ETDRS BCVA letter score of [-3.5 to 3.5], supporting the demonstration of comparative efficacy. Secondary efficacy outcomes were also comparable. PK analyses supported systemic safety. There were no clinically meaningful differences in immunogenicity profiles. Safety profiles were similar; most treatment-emergent adverse events were mild and unrelated to the study drug. CONCLUSIONS: Results supported a demonstration of comparable efficacy between AVT06 and RP aflibercept. Similar PK, immunogenicity, and safety profiles were also shown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT05155293; ClinicalTrialsRegister.eu identifier is 2021-003651-42.
INTRODUCTION: There has been a giant leap forward in the management of Hodgkin's lymphoma (HL) over the past decade. Emergence of long-term data from large, randomized trials in early-stage disease (eHL) and incorporatio...INTRODUCTION: There has been a giant leap forward in the management of Hodgkin's lymphoma (HL) over the past decade. Emergence of long-term data from large, randomized trials in early-stage disease (eHL) and incorporation of brentuximab vedotin (BV) or nivolumab into the frontline setting through three large phase-3 trials in advanced stages (aHL) are driving the paradigm shift in HL. The new landscape promises chances of cure to over 90% newly diagnosed patients while maintaining caution for long-term toxicity. AREAS COVERED: This review will cover the published evidence regarding primary analyses or updates within the last 5 years on phase-3 clinical trials conducted in the frontline treatment setting for HL. Concerning areas of clinical significance where no comparative trial data is available, data from phase-2 trials or real-world analyses will be briefly discussed. EXPERT OPINION: Consolidative radiotherapy is no longer a strict necessity in eHL cases with complete response to frontline chemotherapy and the decision to irradiate in such cases should be individualized. The state-of-the-art in managing aHL requires the use of either BV or nivolumab as introduced by the GHSG HD21 and SWOG S1826 trials, respectively.