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OBJECTIVES: Anti-vascular endothelial growth factor (VEGF) therapy restores retinal architecture and enhances vision in diabetic macular edema (DME). Bevacizumab is an off-label anti-VEGF drug that effectively treats DME. The safety and efficacy of bevacizumab biosimilars, which are more affordable than the original medication, still need to be established. This study aimed to assess the cost-effectiveness, efficacy, and safety of biosimilars for treating patients with naïve DME across various price ranges that are accessible in the Indian market. MATERIALS AND METHODS: Two biosimilars, BevaciRelTM (Reliance Life Sciences Pvt. Ltd.) and ZyBev (Cadila Healthcare Limited), were compared to their original, Avastin (Roche Products [India] Pvt. Ltd.), in a randomized, control study. Three end-notes were used to assess safety and efficacy: persistence, improvement, and adverse events. Cost-effective analysis was carried out using a decision-tree analysis model. RESULTS: This study included 69 (59%) men and 54 (41%) women with naïve DME. The cohort had an average log MAR visual acuity of 0.87 ± 0.22, and the central retinal thickness at baseline on OCT was 398.5 ± 37.61 µm. The visual acuity showed a similar improvement, and there was a decrease in central retinal thickness as observed on OCT across the groups. The incremental cost-effectiveness ratio was 10.8. CONCLUSIONS: The biosimilars of bevacizumab are safe and efficacious in treating DME in a cost-effective manner.

Asunto(s)

Inhibidores de la Angiogénesis , Bevacizumab , Biosimilares Farmacéuticos , Análisis Costo-Beneficio , Retinopatía Diabética , Edema Macular , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/economía , Edema Macular/tratamiento farmacológico , Biosimilares Farmacéuticos/economía , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Masculino , Femenino , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/economía , Inhibidores de la Angiogénesis/economía , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Agudeza Visual , India , Adulto

RESUMEN

BACKGROUND: Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24-48). METHODS: In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. RESULTS: Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. CONCLUSION: In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. TRIAL REGISTRATION: NCT03830203 and EudraCT 2018-002202-31.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Antirreumáticos , Artritis Reumatoide , Biosimilares Farmacéuticos , Metotrexato , Humanos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Metotrexato/uso terapéutico , Metotrexato/farmacocinética , Metotrexato/administración & dosificación , Femenino , Método Doble Ciego , Persona de Mediana Edad , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Adulto , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Resultado del Tratamiento , Anciano , Índice de Severidad de la Enfermedad

RESUMEN

Purpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects. Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints. Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00-125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab. Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar. Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).

Asunto(s)

Anticuerpos Monoclonales Humanizados , Biosimilares Farmacéuticos , Voluntarios Sanos , Humanos , Masculino , Método Doble Ciego , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/administración & dosificación , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/efectos adversos , Adulto , Adulto Joven , Pueblo Asiatico , China , Persona de Mediana Edad , Equivalencia Terapéutica , Pueblos del Este de Asia

RESUMEN

This study presents a safety analysis of infusion reactions (IRs) in gastric cancer patients who switched from reference trastuzumab to its biosimilar, trastuzumab-NK, at the Saitama Cancer Center in Japan from April 2018 to March 2022. IRs were identified if patients developed symptoms such as fever, chills, infusion-related reactions, hypersensitivity, rash, pruritus, urticaria, systemic disorders, or immune system disorders on the day of administration or the following day. The incidence of IRs was 14% in the reference trastuzumab group, 33% in the trastuzumab-NK group, and 33% in the switching group. There was no significant difference in IR incidence between the reference trastuzumab and trastuzumab-NK groups (p = 0.235). Among the switching group, only one of the three patients who experienced an IR had a reaction associated with the switch. These findings suggest that the frequency of IRs in the switching group gastric cancer is comparable to the other groups, indicating that switching is a viable treatment option with appropriate management. Additionally, 37 of the 45 patients in the study were male, provides new safety information on switching in gastric cancer for male patients that has not been previously reported.

Asunto(s)

Biosimilares Farmacéuticos , Receptor ErbB-2 , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Masculino , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Femenino , Persona de Mediana Edad , Anciano , Receptor ErbB-2/metabolismo , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Adulto , Japón , Anciano de 80 o más Años , Sustitución de Medicamentos , Infusiones Intravenosas

RESUMEN

This was a Phase I, randomized, double-blinded, three-arm, single-dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU-reference] and United States [US-reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC0-last); and maximum observed serum concentration (Cmax). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC0-∞), time to reach maximum observed concentration, clearance, terminal phase half-life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. Cmax was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half-live across treatment arms. Systemic exposure of MB09 (AUC0-last and Cmax) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C-terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment-emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products.

Asunto(s)

Biosimilares Farmacéuticos , Denosumab , Voluntarios Sanos , Humanos , Denosumab/farmacocinética , Denosumab/administración & dosificación , Denosumab/efectos adversos , Masculino , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Adulto , Método Doble Ciego , Persona de Mediana Edad , Adulto Joven , Área Bajo la Curva , Conservadores de la Densidad Ósea/farmacocinética , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Equivalencia Terapéutica , Adolescente , Inyecciones Subcutáneas , Semivida

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INTRODUCTION: To evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups. RESULTS: In the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (-12.19%, 3.11%) for the difference in ORR (-4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups. CONCLUSION: Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Biosimilares Farmacéuticos , Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Método Doble Ciego , India , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/farmacocinética , Resultado del Tratamiento , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Docetaxel/uso terapéutico , Docetaxel/administración & dosificación

RESUMEN

The paper highlights the necessity for a robust regulatory framework for assessing nanomedicines and their off-patent counterparts, termed as nanosimilar, which could be considered as 'similar' to the prototype nanomedicine,based on essential criteria describing the 'similarity'. The term 'similarity' should be focused on criteria that describe nanocarriers, encompassing their physicochemical, thermodynamic, morphological, and biological properties, including surface interactions and pharmacokinetics. Nanocarriers can be regarded as advanced self-assembled excipients (ASAEs) due to their complexity and chaotic behavior and should be evaluated by using essential criteria in order for off-patent nanomedicines be termed as nanosimilars, from a regulatory perspective. Collaboration between the pharmaceutical industry, regulatory bodies, and artificial intelligence (AI) startups is pivotal for the precise characterization and approval processes for nanomedicines and nanosimilars and embracing innovative tools and terminology facilitates the development of a sustainable regulatory framework, ensuring safety and efficacy. This crucial shift toward precision R&D practices addresses the complexity inherent in nanocarriers, paving the way for therapeutic advancements with economic benefits.

Asunto(s)

Nanomedicina , Nanomedicina/legislación & jurisprudencia , Nanomedicina/métodos , Humanos , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/farmacocinética , Inteligencia Artificial , Nanopartículas , Industria Farmacéutica/legislación & jurisprudencia , Aprobación de Drogas/legislación & jurisprudencia , Portadores de Fármacos/química

RESUMEN

INTRODUCTION: Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers. METHODS: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication. RESULTS: Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX. CONCLUSIONS: Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42021289144.

Asunto(s)

Biosimilares Farmacéuticos , Sustitución de Medicamentos , Fármacos Gastrointestinales , Enfermedades Inflamatorias del Intestino , Infliximab , Humanos , Infliximab/efectos adversos , Infliximab/uso terapéutico , Infliximab/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/economía , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/administración & dosificación , Resultado del Tratamiento

RESUMEN

INTRODUCTION: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO). METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product. RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study. CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.

Asunto(s)

Inyecciones Intravítreas , Edema Macular , Ranibizumab , Oclusión de la Vena Retiniana , Jeringas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/complicaciones , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Ranibizumab/administración & dosificación , Ranibizumab/uso terapéutico , Enfermedades de la Retina/tratamiento farmacológico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/complicaciones

RESUMEN

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Asunto(s)

Adalimumab , Antirreumáticos , Biosimilares Farmacéuticos , Etanercept , Sistema de Registros , Enfermedades Reumáticas , Humanos , Femenino , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Adalimumab/uso terapéutico , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Etanercept/uso terapéutico , Etanercept/administración & dosificación , Adulto , Anciano , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/mortalidad , Estudios Prospectivos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Resultado del Tratamiento , Inyecciones Subcutáneas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , España/epidemiología

RESUMEN

BACKGROUND: This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS: Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS: Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS: QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION: Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Biosimilares Farmacéuticos , Neoplasias de la Mama , Docetaxel , Terapia Neoadyuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Docetaxel/administración & dosificación , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Método Doble Ciego , Adulto , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/uso terapéutico , Anciano , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo

RESUMEN

BACKGROUND: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the first line treatments for diffuse large B-cell lymphoma (DLBCL). Rituximab comprises most of the treatment cost for this regimen; therefore, biosimilars, such as rituximab-abbs are crucial to provide affordable care. Although rituximab-abbs was studied primarily in follicular lymphoma, the Food and Drug Administration (FDA) approved this drug for all indications of the reference product on the basis of extrapolation. Effectiveness and safety data surrounding the use of rituximab-abbs in DLBCL is lacking. OBJECTIVE: To evaluate the effectiveness and safety of rituximab-abbs and reference product rituximab as R-CHOP treatment for patients with DLBCL. PATIENTS AND METHODS: This noninferiority (NI) study compared the 2-year overall survival (OS), overall response rate (ORR), and incidence of adverse events (AEs) between rituximab-abbs and its reference product (RP) in R-CHOP among adult patients with newly diagnosed DLBCL. The study inclusion period was from 1 January 2019 to 31 December 2020. Analyses were performed on the basis of a noninferiority lower limit of 10% for OS and ORR, and an upper limit of 10% for serious AEs. RESULTS: There were 240 patients who received RP rituximab, while 295 patients received rituximab-abbs. The cohort had a mean age of 63.7±12.2 years and 43% were female. The 2-year OS was 81.0% and 79.6% (NI p < 0.01) while the ORR was 80.0% and 69.6% (NI p < 0.01), among the rituximab-abbs and rituximab groups, respectively. The incidence of infusion reaction AEs (NI p < 0.01) and noninfusion reaction AEs (NI p < 0.01) also met noninferiority. CONCLUSIONS: We demonstrated that rituximab-abbs was noninferior to rituximab in both effectiveness and safety among patients receiving R-CHOP for DLBCL in this study. Long-term follow-up would be needed to confirm these results.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma de Células B Grandes Difuso , Prednisona , Rituximab , Vincristina , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Anciano , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Vincristina/uso terapéutico , Vincristina/efectos adversos , Vincristina/administración & dosificación , Adulto , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/administración & dosificación , Resultado del Tratamiento , Anciano de 80 o más Años

RESUMEN

To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.

Asunto(s)

Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Agudeza Visual , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Masculino , Femenino , Anciano , Agudeza Visual/efectos de los fármacos , Resultado del Tratamiento , Degeneración Macular/tratamiento farmacológico , Persona de Mediana Edad , Método Doble Ciego , Anciano de 80 o más Años , Neovascularización Coroidal/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación

RESUMEN

BACKGROUND AND OBJECTIVE: Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02, a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as a trastuzumab biosimilar. The objective of this study was to evaluate the equivalence of BP02 with reference trastuzumab (RT: Herceptin®-EU) in patients with HER2-positive metastatic breast cancer. METHODS: This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75 mg/m2 on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ± 13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively. CONCLUSIONS: BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks. CLINICAL TRIAL REGISTRATION: CTRI Number: CTRI/2020/04/024456.

Asunto(s)

Biosimilares Farmacéuticos , Neoplasias de la Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Persona de Mediana Edad , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacología , Receptor ErbB-2/metabolismo , Adulto , Método Doble Ciego , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Anciano , Adulto Joven , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Adolescente , Docetaxel/uso terapéutico , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Metástasis de la Neoplasia , India , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos

RESUMEN

BACKGROUND: This study compared the pharmacokinetics (PK), immunogenicity, and safety of candidate tocilizumab biosimilar, CT-P47, administered via auto-injector (CT-P47 AI) or pre-filled syringe (CT-P47 PFS), in healthy Asian adults. RESEARCH DESIGN AND METHODS: In this phase I, multicenter, open-label study, participants were randomized 1:1 to receive a single 162 mg/0.9 mL dose of CT-P47 via AI or PFS. Primary endpoints were area under the concentration - time curve from time zero to infinity (AUC0-inf) and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK parameters, immunogenicity, and safety outcomes were also assessed. RESULTS: Of 314 participants randomized (155 CT-P47 AI; 159 CT-P47 PFS), 310 received the study drug (153 CT-P47 AI; 157 CT-P47 PFS). Primary and secondary PK results, immunogenicity and safety were similar between groups. Ninety percent CIs for the ratio of gLSMs were within the predefined equivalence margin for AUC0-inf (85.87-102.94) and Cmax (82.98-98.16). CONCLUSIONS: PK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05617183.

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Tocilizumab is a biologic medicine used to treat inflammatory diseases, such as rheumatoid arthritis. A biosimilar is a drug that is an almost identical copy of an approved original ('reference') biologic medicine; it has identical efficacy and safety to the original medicine but is typically less expensive. CT­P47 is in development as a possible tocilizumab biosimilar.Some patients prefer injections using an auto-injector (AI) rather than a pre-filled syringe (PFS), for reasons including ease of use and convenience. With an AI, medicine is delivered automatically by firmly pressing the device against the skin, whereas, with a PFS, a needle is inserted into the skin and medicine delivered by depressing the plunger. The injection of CT­P47 using a PFS has shown comparable pharmacokinetics (i.e., the uptake, metabolism and excretion of the drug by the body) and safety to tocilizumab. Therefore, if the pharmacokinetics and safety of CT­P47 administered via AI and PFS were shown to be similar, this might expand the choice of administration devices available to patients.In this study, 310 healthy adults received a single injection of CT­P47 via AI or PFS. Blood samples were taken over 43 days to analyze pharmacokinetics. The uptake, metabolism and elimination of CT­P47 by the body was similar when administered by each device, suggesting that CT­P47 can be administered by either AI or PFS.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Biosimilares Farmacéuticos , Jeringas , Humanos , Masculino , Adulto , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Femenino , Persona de Mediana Edad , Adulto Joven , Área Bajo la Curva , Autoadministración/instrumentación , Equivalencia Terapéutica

RESUMEN

PURPOSE: Wet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF). METHODS: Bevacizumab, or biosimilar ranibizumab was diluted to 5 mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100 µl eye drops): Group 1 (bevacizumab/AAF, n = 6); Group 2 (bevacizumab/PBS, n = 7) and Vehicle control (AAF, n = 1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50 µl eye drops): (ranibizumab biosimilar/AAF, n = 8). At 14.5 days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent. RESULTS: Bevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28 ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (< 0.04 ng/ml). No irritation was observed throughout the studies. CONCLUSIONS: Bevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.

Asunto(s)

Bevacizumab , Soluciones Oftálmicas , Ranibizumab , Retina , Animales , Ranibizumab/administración & dosificación , Ranibizumab/farmacocinética , Conejos , Bevacizumab/administración & dosificación , Bevacizumab/farmacocinética , Soluciones Oftálmicas/administración & dosificación , Retina/metabolismo , Retina/efectos de los fármacos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacocinética , Cuerpo Vítreo/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inyecciones Intravítreas , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/farmacocinética , Degeneración Macular Húmeda/tratamiento farmacológico

RESUMEN

OBJECTIVE: In our study, we analyzed the efficacy and safety data of patients with systemic lupus erythematosus (SLE) after switching to biosimilar rituximab (RTX). PATIENTS AND METHODS: Twenty-two patients who switched to RTX were included in the study. Efficacy data were analyzed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and safety data were analyzed using the frequency of side effects. RESULTS: The mean treatment duration of originator RTX was 35.6 ± 23.0 months, and the median treatment duration of biosimilar RTX was 17 months. The SLEDAI-2K score, approximately three months after the first dose of biosimilar RTX, was significantly lower (p = 0.027). A statistically significant difference was found between the SLEDAI-2K score assessed at the follow-up visit three months after the last dose of originator RTX and the SLEDAI-2K score obtained approximately three months after the first dose of biosimilar RTX (p = 0.011) and the calculated median SLEDAI-2K score was significantly lower than the SLEDAI-2K score assessed after administration of originator RTX. The side effect frequency that developed during the treatment of originator RTX was 15.3 per 100 patient-years. The most common side effect was infection, which was 15.3 per 100 patient-years. The most frequent infection was urinary tract infection. The side effect frequency during treatment of biosimilar RTX was 39 per 100 patient-years, and the most frequent infection was pneumonia. CONCLUSIONS: In our study, SLEDAI-2K scores demonstrated that no efficacy loss was experienced after switching to CT-P10 molecule, which is a biosimilar RTX. It was observed that switching to biosimilar RTX did not decrease treatment efficacy in the patient group diagnosed with SLE and biosimilar RTX was found to be safe.

Asunto(s)

Biosimilares Farmacéuticos , Lupus Eritematoso Sistémico , Rituximab , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/diagnóstico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Sustitución de Medicamentos , Anticuerpos Monoclonales de Origen Murino

RESUMEN

The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1ß, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals.

Asunto(s)

Biosimilares Farmacéuticos , Estudios Cruzados , Citocinas , Equivalencia Terapéutica , Trastuzumab , Humanos , Trastuzumab/farmacocinética , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/administración & dosificación , Masculino , Adulto , Citocinas/metabolismo , Citocinas/sangre , Método Doble Ciego , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Inmunomodulación/efectos de los fármacos , Adulto Joven

RESUMEN

Rituximab is a monoclonal antibody that targets CD20 antigen in B cells. For pemphigus, rituximab has been highly effective in steroid-sparing therapy for moderate to severe cases. Originator rituximab has demonstrated favorable treatment effects in patients with pemphigus, but its high cost remains a challenge. Biosimilar rituximab is expected to offer a potential solution. However, it is required for the comparative study of efficacy and safety between biosimilar and originator because all biosimilars may not be identical to the originator. In this study, we compared the treatment effects and safety of biosimilar (Truxima) and originator (MabThera) rituximab in patients with pemphigus. A final cohort of 52 patients in the MabThera group and 72 patients in the Truxima group was enrolled. Except for the intravenous immunoglobulin administration rate, there were no differences in baseline characteristics between the two groups, and for the purpose of comparing efficacy, investigations into time to complete remission, total steroid intake to complete remission, and total steroid intake for 6 months following rituximab treatment revealed no significant differences between the two groups. Truxima can be considered a relatively affordable alternative treatment option for pemphigus, offering cost-effectiveness to patients who are indicated for the treatment with MabThera.

Asunto(s)

Biosimilares Farmacéuticos , Pénfigo , Rituximab , Humanos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Pénfigo/tratamiento farmacológico , Pénfigo/inmunología , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/economía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/administración & dosificación , Inducción de Remisión/métodos , Estudios Retrospectivos

RESUMEN

OBJECTIVE: MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in healthy volunteers or in patients with psoriasis or rheumatoid arthritis (RA). This is the first study conducted under clinical practice conditions evaluating the switch from reference adalimumab to MSB11022 in patients with RA. METHODS: Retrospective and multicenter study with data from the medical records of patients with RA who switched from reference adalimumab or another biosimilar to MSB11022 and maintained this treatment for at least 6 months. Information registered comes from baseline visit, the moment of the switch, and the follow-up visits. RESULTS: Data from 86 patients were evaluated (median age 63.5 years, 75.6% female, 44.2% had erosive RA). Only 3.5% of the patients received biologic therapy prior to adalimumab. At baseline, median DAS28-CRP was 1.77 (80.2% in remission and 96.5% with low disease activity) and median CDAI was 4.00 (44.2% in remission and 90.7% with low disease activity). After a median follow-up of 8 months, median DAS28-CRP was 1.87 (86.0% in remission and 94.2% with low disease activity) and median CDAI was 4.00 (38.5% in remission and 95.3% with low disease activity). Only three patients experienced pain, swelling, and stinging at the injection site or a locally extensive hematoma in the area of administration. CONCLUSIONS: Adalimumab biosimilar MSB11022 maintained the efficacy benefits provided by previous adalimumab treatments with a safety profile in line with that already described for other biosimilars.

Asunto(s)

Adalimumab , Antirreumáticos , Artritis Reumatoide , Biosimilares Farmacéuticos , Sistema de Registros , Humanos , Adalimumab/administración & dosificación , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Femenino , Persona de Mediana Edad , Masculino , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Anciano , España , Estudios Retrospectivos , Resultado del Tratamiento , Sustitución de Medicamentos/estadística & datos numéricos , Adulto