INTRODUCTION: Recombinant human erythropoietin (rHuEPO) and its derivatives, which are called erythropoiesis-stimulating agents (ESAs), have long been indispensable molecules to treat patients with anemia due to their hi...INTRODUCTION: Recombinant human erythropoietin (rHuEPO) and its derivatives, which are called erythropoiesis-stimulating agents (ESAs), have long been indispensable molecules to treat patients with anemia due to their high effectiveness in stimulating erythropoiesis. Previous studies have indicated the additional effects of EPO besides erythropoiesis such as suppressing inflammation and apoptosis. AREAS COVERED: This review summarizes the physiology of EPO and its receptors, describes the pathways other than erythropoiesis activated by recombinant human EPO and their derivatives, and discusses the potential benefits of non-erythropoietic EPO receptor agonists (ERAs). Literature search was conducted using Google Scholar and PubMed databases. EXPERT OPINION: Previous studies indicate the protective effects of ESAs in various disease models, some of which are independent of their erythropoietic feature. However, ESAs contain safety concerns, especially when administered in high dose to fully bring out their favorable effects. ERAs that only activate the non-erythropoietic reactions by EPO seem to be equally beneficial in improving outcome without serious adverse effects, which raises expectations for their further investigation in large clinical trials. So far, non-erythropoietic ERAs are not clinically available yet, and clinicians should understand the risks associated with ESAs upon their usage.
BACKGROUND: Anti-IL-23 monoclonal antibodies have shown strong efficacy in achieving complete clearance (PASI 100) in psoriasis. Real-world evidence is needed to confirm these outcomes and define predictors of response....BACKGROUND: Anti-IL-23 monoclonal antibodies have shown strong efficacy in achieving complete clearance (PASI 100) in psoriasis. Real-world evidence is needed to confirm these outcomes and define predictors of response. RESEARCH DESIGN AND METHODS: We performed a monocentric retrospective study on 243 adults with moderate-to-severe psoriasis treated with guselkumab, risankizumab, or tildrakizumab at the University of Pisa. The primary endpoint was PASI 100 achievement; secondary endpoints were maintenance and predictors of response. Survival analysis and Cox regression were applied. RESULTS: PASI 100 was achieved in 67.4% of patients, on average at 27 weeks. Among responders, 81.7% maintained clearance for a mean of 90 weeks. Palmoplantar involvement reduced the likelihood of achieving PASI 100 (HR 0.575), while facial involvement (HR 2.261) and longer disease duration (HR 1.020) favored maintenance. Prior cyclosporine use (HR 0.644) and higher baseline PASI (HR 0.973) were negative predictors. No unexpected safety issues were observed. CONCLUSIONS: Anti-IL-23 therapies are effective in achieving and sustaining PASI 100 in routine care. Outcomes are influenced by disease localization, duration, prior treatments, and baseline severity. Limitations include retrospective design, single-center setting, and absence of comparators.
Soardo F, Spini A, L'Abbate L
… +30 more, Bellitto C, Pellegrini G, Ingrasciotta Y, Paladin A, di Spazio L, Campomori A, Urru SAM, Leoni O, Zanforlini M, Ancona D, Stella P, Cavazzana A, Scapin A, Lopes S, Belleudi V, Ledda S, Carta P, Rossi P, Ejlli L, Sapigni E, Puccini A, Trama U, Bernardi FF, Mangano AMP, Balducci F, Spila-Alegiani S, Massari M, Alberti C, Krampera M, Trifirò G
OBJECTIVES: To assess the use of rituximab in non-Hodgkin lymphoma (nHL) and chronic lymphocytic leukemia (CLL) in light of the evolving regulatory landscape, including the introduction of subcutaneous and biosimilar for...OBJECTIVES: To assess the use of rituximab in non-Hodgkin lymphoma (nHL) and chronic lymphocytic leukemia (CLL) in light of the evolving regulatory landscape, including the introduction of subcutaneous and biosimilar formulations in the past decade. METHODS: A retrospective cohort study was conducted using the VALORE distributed database network covering nine Italian regions (2012-2022). Patients with at least one rituximab dispensing and a previous nHL or CLL diagnosis were included. Annual prevalence rates (per 10,000 inhabitants) were estimated for intravenous originator, biosimilar, and subcutaneous formulations. Switch rates between originator and biosimilar were assessed by index year at 1 year of follow-up. RESULTS: We selected 73,870 prevalent rituximab users. Prevalence peaked in 2019 (4.6/10,000) and declined in 2022 (3.4/10,000), with originator use dropping from 4.2 to 0.2/10,000. Among 24,258 incident users (nHL: 21,001; CLL: 3,257), originator-to-biosimilar switch rates rose from 12.5% (2017) to 33.3% (2022) in nHL ( < 0.05) and from 10.3% (2017) to 78.3% (2020) in CLL ( < 0.05). Biosimilar-to-originator switches were rare in CLL (3.8%) but more frequent in nHL (15.3%), due to subcutaneous switch. CONCLUSIONS: These findings show a shift from originator to biosimilar rituximab in Italy, alongside a recent decline in its use, likely driven by COVID-19 pandemic and new treatment strategies.
INTRODUCTION: Medical management of juvenile idiopathic arthritis (JIA) presents a significant challenge in pediatric rheumatology. Ideally, the treatment target is remission, though achieving this remains complex. Inter...INTRODUCTION: Medical management of juvenile idiopathic arthritis (JIA) presents a significant challenge in pediatric rheumatology. Ideally, the treatment target is remission, though achieving this remains complex. Interleukin-6 (IL-6) inhibitors (IL-6is) play an important role, targeting the inflammatory pathways central to JIA pathogenesis. However, their optimal use is debated. AREAS COVERED: This narrative review examined JIA care needs and IL-6 inhibition. A SPIDER-based literature search of PubMed/MEDLINE, Semantic Scholar, WorldCat, Cochrane Library, Embase, CINAHL, ICTRP, and ClinicalTrials.gov (to May 2025), identifying 56 studies from 246 records published between 2018 and 2025. Key unmet needs include difficulty controlling the disease, diagnostic delay, shortcomings in biomarker research, and multidisciplinary support. Tocilizumab, a well-studied IL6i, showed efficacy in symptom reduction, disease control, and reduced glucocorticoid use. EXPERT OPINION: Addressing gaps in JIA management, such as delayed diagnosis and inadequate disease control, is essential. Experts advocate for early IL6i use within a treat-to-target framework, optimizing outcomes and minimizing glucocorticoid use. Recognizing benefits for highrisk JIA subtypes, experts support earlier tocilizumab integration into treatment algorithms, offering valuable options for refractory oligoarthritis and uveitis. Ultimately, bridging gaps in JIA management and reshaping real-world outcomes hinges on integrating clinical insight and research outcomes - a process driven by precision medicine.
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, Wolff-Holz E, Athalye SN
BACKGROUND: The STELLAR-2 study compared the efficacy, safety, immunogenicity, and pharmacokinetics of Bmab 1200 with reference ustekinumab through Week 52 in patients with moderate-to-severe chronic plaque psoriasis. RE...BACKGROUND: The STELLAR-2 study compared the efficacy, safety, immunogenicity, and pharmacokinetics of Bmab 1200 with reference ustekinumab through Week 52 in patients with moderate-to-severe chronic plaque psoriasis. RESEARCH DESIGN AND METHODS: In this double-blind, Phase 3 study, patients were randomized 1:1 to receive Bmab 1200 or reference ustekinumab (45 mg or 90 mg). At Week 16, patients responding to ustekinumab (improvement in Psoriasis Area and Severity Index [PASI] score ≥50%) were re-randomized to continue with reference ustekinumab or switch to Bmab 1200 and followed through Week 52. RESULTS: Overall, 324 patients completed the study. At Week 52, the mean (SD) percentage reduction in PASI scores from baseline was -95.5% (7.51) for Bmab 1200, -96.6% (5.67) for continued-reference ustekinumab, and -94.7% (7.95) for switched-to-Bmab 1200 groups. Efficacy and safety outcomes were comparable across groups. From 28 to 52 weeks, 37.8% of patients had at least one treatment-emergent adverse event. The incidence of post-switch antidrug antibodies was also comparable (Bmab 1200: 63.7%; continued-reference ustekinumab: 80.2%; switched-to-Bmab 1200: 72.6%). CONCLUSIONS: Bmab 1200 demonstrated clinical biosimilarity to reference ustekinumab through Week 52 even after switching. Long-term comparable efficacy and safety were also maintained. TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05335356 and www.clinicaltrialsregister.eu identifier is 2021-006668-25.
INTRODUCTION: Advances in frontline multiple myeloma (MM) treatment, through combinatorial regimens with diverse mechanisms of action, have created a need for alternative agents at relapse. BCMA-targeting CAR-T therapies...INTRODUCTION: Advances in frontline multiple myeloma (MM) treatment, through combinatorial regimens with diverse mechanisms of action, have created a need for alternative agents at relapse. BCMA-targeting CAR-T therapies have already demonstrated superiority over conventional options. Belantamab mafodotin, a first-in-class BCMA-directed antibody - drug conjugate (ADC), has shown significant benefit in combination with proteasome inhibitors or immunomodulators, as an accessible alternative to CAR-T therapy. AREAS COVERED: Belantamab mafodotin-based regimens were approved for the treatment of MM from second line of therapy in UK (April 2025) and EU (July 2025) and is under extended review by the FDA after concerns raised regarding its safety profile. This review discusses its mechanism of action, along with efficacy and safety data, to evaluate its role in the evolving MM treatment landscape. EXPERT OPINION: Belantamab mafodotin offers a distinct therapeutic profile: off-the-shelf availability compared to CAR-Ts, lower infection risk than T-cell engagers, and a mechanism of action distinct from both T-cell - redirecting and standard therapies. Ocular keratopathy is a class-specific adverse event that is manageable with appropriate measures. Its relatively low incidence of life-threatening infections supports its use, particularly in frail patients. Ongoing trials suggest a feasible integration into frontline regimens to further improve clinical outcomes.
OBJECTIVE: Biologic agents have been used in colchicine-resistant familial Mediterranean fever (FMF) patients and in patients with comorbidities including juvenile idiopathic arthritis (JIA). The main aim of our study wa...OBJECTIVE: Biologic agents have been used in colchicine-resistant familial Mediterranean fever (FMF) patients and in patients with comorbidities including juvenile idiopathic arthritis (JIA). The main aim of our study was to evaluate the use of biological agents in pediatric patients with FMF and to assess the factors influencing the initiation of biological treatment. MATERIALS AND METHODS: Our study included 832 pediatric FMF patients, who were followed up at Ankara Etlik City Hospital. Demographic data, clinical and laboratory characteristics, genetic results, treatments and treatment responses of the patients were retrospectively reviewed. RESULTS: Of the patients enrolled in the study, 107 (12.9%) had received biological treatment. The reduction in attack frequency and changes in laboratory parameters including white blood cell count, absolute neutrophil count, neutrophil/lymphocyte ratio, hemoglobin, platelet count, mean platelet volume, C-reactive protein, erythrocyte sedimentation rate and serum amyloid A levels were statistically significant in patients receiving (anti-interleukin-1) treatment. CONCLUSION: The initiation of biological treatment was higher in patients with younger symptom onset, in patients with JIA comorbidity, and in patients with homozygous exon 10 or compound heterozygous exon 10 mutation. Gender, delay in diagnosis, comorbidities other than JIA, family history of FMF, amyloidosis or chronic kidney disease did not increase the initiation of biological treatment.
BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel di...BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information. RESEARCH DESIGN AND METHODS: Readability was calculated using Readable software, examining (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index, and (iv) SMOG Index and two text metrics [words/sentence, syllables/word] for 234 sources of FMT information, from four categories (abstracts/hospital information/patient-facing information/clinical trials). RESULTS: Mean readability scores of FMT information for FRE and FKGL were 22.2 ± 1.2 (SEM) (target > 60) and 14.8 ± 0.2 (target < 8), respectively, with mean words/sentence and syllables/word of 19.2 ± 0.4 and 2.0, respectively. There was no significant difference in readability between scientific abstracts and lay summaries. No information was found that had a readability of less than 7th grade (12-13 year olds). CONCLUSION: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.
INTRODUCTION: Complement inhibition has revolutionized paroxysmal nocturnal hemoglobinuria (PNH) treatment. While eculizumab, the first anti-C5 antibody, reduced intravascular hemolysis (IVH) and thrombotic risk, it requ...INTRODUCTION: Complement inhibition has revolutionized paroxysmal nocturnal hemoglobinuria (PNH) treatment. While eculizumab, the first anti-C5 antibody, reduced intravascular hemolysis (IVH) and thrombotic risk, it required fortnightly infusions and left a significant percentage of patients with persistent anemia. New terminal complement inhibitors, such as long-acting ravulizumab and subcutaneous crovalimab, have allowed for better control of IVH and demonstrated efficacy in patients with specific C5 genetic polymorphisms (crovalimab). Proximal complement inhibitors, including the small molecule pegcetacoplan (C3 inhibitor), the recently approved orally administered iptacopan (factor B inhibitor), and danicopan (factor D inhibitor, in combination with anti-C5), efficiently control C3-mediated extravascular hemolysis. However, these treatments come with an increased risk of serious breakthrough hemolysis events due to reduced half-life and increased sparing of PNH erythrocytes. AREAS COVERED: In this review, we summarize phase III trials and real-world data to support patient-tailored treatment strategies and offer practical guidance for patient profiling and optimal complement inhibitor selection. EXPERT OPINION: In this evolving landscape, treatment choice has become increasingly complex. PNH specialists must now balance multiple factors beyond efficacy alone. Disease characteristics such as previous thrombotic events or transfusion needs, as well as drug administration routes, patient preferences toward oral or parenteral administration and expected compliance, will all influence clinical decisions.
BACKGROUND: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the Tocilizumab biosimilar, BAT1806 SC (Tocilizumab biosimilar, Subcutaneous Injection), with Tocilizumab (RoActemra®) in healthy C...BACKGROUND: This study compared the pharmacokinetics (PK), safety, and immunogenicity of the Tocilizumab biosimilar, BAT1806 SC (Tocilizumab biosimilar, Subcutaneous Injection), with Tocilizumab (RoActemra®) in healthy Chinese male subjects. RESEARCH DESIGN AND METHODS: In this randomized, double-blind, parallel-group phase I clinical study, healthy Chinese male subjects (Number (N) = 300) were randomized 1:1 to receive 162 mg/0.9 mL either BAT1806 SC or Tocilizumab subcutaneously. RESULTS: The mean drug concentration-time curve trend and PK parameters were similar between BAT1806 SC and Tocilizumab. The 90% CIs (Confidence Interval), of the GMRs (Geometric Mean Ratio) of AUC (area under the curve from zero to infinity) (97.07%), and AUC (area under the curve from time 0 to the last measured) (97.18%) and C (95.72%) were all within the bioequivalence limits [80.00%-125.00%]. The TEAE was very similar between the BAT1806 SC group (89.4%) and the Tocilizumab group (91.3%). No serious adverse events such as TEAEs (Treatment-related adverse events) leading to early discontinuation or deaths were reported. The ADA (anti-drug antibodies) incidence was 67 (44.4%) and 49 (32.9%) in the BAT1806 SC group and Tocilizumab group. This study revealed that immunogenicity had no significant effect on the PK or safety of the Tocilizumab. CONCLUSION: This study demonstrated bioequivalent PK, comparable safety, and immunogenicity profiles of BAT1806 SC and Tocilizumab in healthy subjects. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05968508).
BACKGROUND: Limited real-world studies have evaluated outcomes after switching treatment from a reference product (RP) to a biosimilar product. The objective of this real-world study was to assess the outcomes of switchi...BACKGROUND: Limited real-world studies have evaluated outcomes after switching treatment from a reference product (RP) to a biosimilar product. The objective of this real-world study was to assess the outcomes of switching from RP adalimumab to biosimilar adalimumab-atto in patients with rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: This was a propensity score matched, non-inferiority study assessing adult patients with RA who switched from RP adalimumab to adalimumab-atto (Switchers) between or received RP adalimumab continuously (Non-Switchers). One-year disease worsening, serious adverse events, and patient out-of-pocket cost outcomes were evaluated. An upper limit of 5% for adalimumab-atto was set as the non-inferiority margin. RESULTS: After matching, there were 1,172 patients in each group. 24.8% and 31.0% of patients in the Switcher and Non-Switcher groups, respectively, experienced the disease worsening (non-inferiority < 0.01). The crude rates per 100 patient-years of the safety outcome and mean monthly changes in out-of-pocket costs were 5.6 (95% CI 4.2-7.5) and 7.2 (95% CI 5.2-9.2) ( = 0.21) and -$51 (±$164) and -$11 (±$152) ( < 0.01) in the Switcher and Non-Switcher groups, respectively. CONCLUSIONS: These results provide evidence that switching from RP adalimumab to biosimilar adalimumab-atto did not result in disease worsening or increased adverse events but did deliver modestly lower patient out-of-pocket costs.
INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies targeting the neuromuscular junction. MG, characterized clinically by fluctuating muscle weakness and fatigability, is traditionally...INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies targeting the neuromuscular junction. MG, characterized clinically by fluctuating muscle weakness and fatigability, is traditionally treated primarily with corticosteroids and nonspecific immunosuppressive drugs. Despite their documented efficacy in a proportion of patients, current standard-of-care treatments are associated with moderate-to-severe side effects that underline the need for new targeted therapies. Nipocalimab, a fully human monoclonal antibody, binds to the neonatal Fc receptor (FcRn) with high affinity and specificity, causing selective reduction of circulating IgG and pathogenic IgG autoantibodies. The phase 3 study Vivacity-MG3 confirmed nipocalimab as an efficacious and safe treatment providing sustained disease control in seropositive patients with generalized MG (gMG). AREAS COVERED: The efficacy and safety of nipocalimab in gMG from the phase 2 study Vivacity-MG (NCT03772587) and the phase 3 study Vivacity-MG3 (NCT04951622). EXPERT OPINION: Clinical studies have demonstrated that nipocalimab provided rapid and sustained reduction of total IgG and pathogenic IgG autoantibodies together with sustained disease control over 6 months in a broad population of seropositive patients with gMG, with an acceptable safety profile. The long-term impact of nipocalimab on the course of gMG needs to be further investigated in real-world settings.
OBJECTIVES: To assess the effectiveness and safety of Rituximab (RTX) treatment among patients diagnosed with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a systematic review...OBJECTIVES: To assess the effectiveness and safety of Rituximab (RTX) treatment among patients diagnosed with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a systematic review with meta-analysis of studies involving patients with RA-ILD who were treated with RTX. Two investigators independently conducted the research. RESULTS: Twenty studies met the criteria for data extraction for the systematic review with a good quality assessment according to an 18-criteria checklist using a modified Delphi method. The total number of patients was 14,523, including 1,619 who received RTX. Stabilization or improvement was observed in more than half of the patients in all studies. Evaluation based on pulmonary function tests (PFTs) noted disease progression in fewer than 20% of 7 out of 11 studies. Meta-analysis results revealed that, based on PFTs, the proportion of patients showing functional decline was 14.5% (95%CI, 7.6-25.8%) (95%PI, 2-69%); and according to the pulmonary high-resolution computed tomography (HRCT) evaluation, the proportion of worsening was 19.5% (95%CI, 8.1-40%) (95%PI, 1-84%). An overall acceptable safety profile was noted, with respiratory mortality ranging from 4% to 14%. CONCLUSION: Our review suggests that RTX appears to be an effective therapy in patients with RA-ILD, with a satisfactory safety profile. PROTOCOL REGISTRATION: https://www.crd.york.ac.uk/prospero identifier is CRD420251049957.
INTRODUCTION: From the 1960s and up until 2021, neoadjuvant chemotherapy has represented the standard of care for potentially resectable stage III (N2) Non-Small Cell Lung Cancer (NSCLC). However, in recent years, immuno...INTRODUCTION: From the 1960s and up until 2021, neoadjuvant chemotherapy has represented the standard of care for potentially resectable stage III (N2) Non-Small Cell Lung Cancer (NSCLC). However, in recent years, immunotherapy in the form of Immune Checkpoint Inhibitors (ICIs) has revolutionized oncology treatment strategies and several ICIs have been investigated for the neoadjuvant treatment of NSCLC, both in monotherapy and in combination with other ICIs or chemotherapy. AREAS COVERED: Therefore, this paper aims to review the currently available data supporting the role of immunotherapy in the neoadjuvant setting, as well as to discuss the challenges associated with it. We undertook a comprehensive literature search of PubMed, Embase, Cochrane Library, of abstracts and posters from annual meetings of American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and American Association for Cancer Research (AACR) up until November 2024. EXPERT OPINION: We believe that in the near future ICI plus chemotherapy combinations will represent the new recommended standard of care in the neoadjuvant/perioperative setting. We look forward to the full results coming from the ongoing randomized phase III trials, that will help us guide our choice in terms of patient selection, regimen of choice, and response assessment.
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with most of patients diagnosed at advanced stage. Thus, systemic therapy remains a cornerstone of treatment. In...INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with most of patients diagnosed at advanced stage. Thus, systemic therapy remains a cornerstone of treatment. In recent years, immunotherapy has changed therapeutic scenario, being investigated also in combination with anti-vascular endothelial growth factor (VEGF) agents. This approach has demonstrated safety and efficacy in several trials, paving the way for their investigation in earlier disease stages and in different settings. AREAS COVERED: A structured literature review was conducted using PubMed and ClinicalTrials.gov to identify published evidence supporting safety and efficacy of anti-programmed death-1/programmed death-ligand-1(PD-1/PD-L1) and anti-VEGF agents in different therapeutic settings and identifying ongoing clinical trials and key research directions. EXPERT OPINION: Combination of anti-PD-1/PD-L1 and anti-VEGF agents has demonstrated safety and efficacy as a first-line treatment for advanced HCC, supported by results from phase 3 trials. These results suggest that further investigation is warranted to optimize first-line efficacy, second-line choice, and potential application in earlier disease stages. The clinical benefit of anti-PD-1/PD-L1 and anti-VEGF agents have also opened the door to a new clinical paradigm, where transitioning from systemic therapy to locoregional therapies, resection or even liver transplantation could be a feasible treatment strategy.
INTRODUCTION: The introduction of biosimilars changed the management of biologicals in inflammatory bowel disease (IBD) since the approval of CT-P13, the first biosimilar to infliximab, by the European Medicines Agency (...INTRODUCTION: The introduction of biosimilars changed the management of biologicals in inflammatory bowel disease (IBD) since the approval of CT-P13, the first biosimilar to infliximab, by the European Medicines Agency (EMA) in September 2013 and by the U.S. Food and Drug Administration (FDA) in April 2016. Accumulating evidence in IBD suggests that biosimilar products have equivalent efficacy and safety to reference products and their use was associated with improved access and decrease in medication costs. AREAS COVERED: This review discusses the current evidence on approved biosimilars of infliximab, adalimumab and ustekinumab in IBD. Authors review data on drug sustainability, efficacy, safety, immunogenicity, non-medical switch data and interchangeability of biosimilar agents. EXPERT OPINION: The biosimilar concept seems to be successful and has led to increased use of biological/biosimilar agents in the treatment of IBD. Clinical trials with biosimilars in IBD and evidence from real world studies on infliximab and adalimumab biosimilars confirm that safety, efficacy and immunogenicity is comparable to the originator, and that switching from the originator or among biosimilars is safe. While payers are supporting mandatory biosimilar use, on the long run the price race can lead to obstacles and unaffordability of the development of new originator biological agents.
INTRODUCTION: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer mortality worldwide, with limited long-term survival despite therapeutic advances. The increasing understanding of its molecular heterog...INTRODUCTION: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer mortality worldwide, with limited long-term survival despite therapeutic advances. The increasing understanding of its molecular heterogeneity has paved the way for precision medicine approaches aiming to optimize treatment efficacy and reduce unnecessary toxicity. AREAS COVERED: This review provides an in-depth analysis of the current and emerging molecular targets in mCRC, including RAS, BRAF, HER2, and microsatellite instability. We discuss the clinical relevance of tumor sidedness, hyperselection panels, EGFR ligand expression, and rare alterations such as NTRK, RET, and ALK fusions. The review also explores the evolving role of KRAS G12C inhibitors, HER2-targeted therapies, and the application of liquid biopsy - particularly circulating tumor DNA (ctDNA) - in treatment monitoring, rechallenge strategies, and resistance detection. Literature was selected through a comprehensive review of recent clinical trials, consensus guidelines, and translational studies. EXPERT OPINION: Personalized treatment is now an attainable goal in mCRC. While promising, broader implementation of molecular-driven strategies requires overcoming challenges such as resistance mechanisms, assay standardization, and equitable access. The integration of innovative agents with real-time molecular monitoring holds the key to a more dynamic and effective management of mCRC.
INTRODUCTION: Zanidatamab is a humanized biparatopic IgG antibody that selectively inhibits HER2 signaling pathway by targeting two distinct epitopes in the extracellular domains II and IV of HER2. Zanidatamab received a...INTRODUCTION: Zanidatamab is a humanized biparatopic IgG antibody that selectively inhibits HER2 signaling pathway by targeting two distinct epitopes in the extracellular domains II and IV of HER2. Zanidatamab received accelerated approval from the United States Food and Drug Administration for the treatment of HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer (BTC) in November 2024. Additionally, zanidatamab received approval for the treatment of HER2 IHC 3+ BTC from the European Medicines Agency in June 2025, and from National Medical Products Administration of China in May 2025. AREAS COVERED: We review the currently available advanced BTC treatments from the perspective of targeted therapy, discuss the implications of HER2 as a therapeutic target in BTC, and discuss the available clinical trial data for zanidatamab for BTC treatment. We then comment on how zanidatamab can fit into the current standard of care for advanced BTC treatment, and the directions of future development strategies. EXPERT OPINION: Zanidatamab appears to be effective for controlling disease progression and maintaining a durable response in patients with previously-treated unresectable or metastatic HER2-positive BTC, with acceptable safety profiles. Based on these favorable data, further investigations using zanidatamab as an earlier line of therapy for BTC are ongoing.