ABSTRACT
Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters. Clinical trial registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).
Subject(s)
Anti-Asthmatic Agents , Asthma , Biosimilar Pharmaceuticals , Omalizumab , Humans , Omalizumab/therapeutic use , Omalizumab/adverse effects , Asthma/drug therapy , Male , Female , Adult , Double-Blind Method , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/adverse effects , Middle Aged , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Treatment Outcome , Therapeutic Equivalency , Immunoglobulin E/blood , Immunoglobulin E/immunology , Young Adult , Severity of Illness IndexABSTRACT
The treatment of patients with rheumatoid arthritis (RA) has dramatically changed in the past 30 years. Currently, numerous conventional, biologic, and targeted synthetic DMARDs have been licensed and used following recommendations provided by international and national scientific societies. However, the availability of biosimilars and the increasing necessity of savings impacted on the local/national prescription of these drugs. The information provided by data sheet of every single drug is a decisive factor on the choice of a certain treatment merged with the patient's profile. Thus, our purpose was to construct a rational algorithm for the treatment strategy in RA according to costs and the product leaflet of the biologic and targeted-synthetic DMARDs currently licensed in Italy. We used the most recent available recommendations and then we performed a review of the literature considering all the factors that are known to influence drug safety/effectiveness. All these factors were considered in the context of the data sheets of currently available originators and biosimilars.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Humans , Algorithms , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/economics , Biosimilar Pharmaceuticals/adverse effects , Drug Labeling , ItalySubject(s)
Biosimilar Pharmaceuticals , Ustekinumab , Humans , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Ustekinumab/therapeutic use , Psoriasis/drug therapy , United States , Dermatologic Agents/therapeutic use , Dermatologic Agents/adverse effects , Dermatologic Agents/pharmacology , Dermatologic Agents/administration & dosage , Drug Approval , United States Food and Drug AdministrationABSTRACT
BACKGROUND: The objective of this phase III clinical randomized trial was to establish the therapeutic equivalence of biosimilar etanercept (bio-etanercept) with original etanercept (O-etanercept) for patients diagnosed with rheumatoid arthritis. METHODS: The study (NCT04079374) enrolled patients with moderate to high disease activity rheumatoid arthritis. Enrolled patients were randomized 1:1 into 2 treatment groups, 1 receiving bio-etanercept (study drug) and the other receiving O-etanercept (comparator) at a dose of 25mg twice weekly, for 24 weeks. The primary efficacy endpoint was the number of patients with an ACR20 response after 24 weeks of treatment. Safety (adverse reaction/adverse event) and immunogenicity of both drugs were evaluated. RESULTS: Among 156 patients (79 in the bio-etanercept group and 77 in the O-etanercept group) who completed 24-week treatment and 4-week follow-up, 82.3% (65 patients) and 90.9% (70 patients) achieved an ACR20 response in the bio-etanercept and O-etanercept groups, respectively. There was no significant difference between the 2 groups (Pâ =â .16). No significant differences in the occurrence of adverse reactions/adverse events were found between the 2 groups regardless of severity (Pâ =â .63 for mild, Pâ =â .43 for moderate and Pâ >â .99 for severe). The development of antibodies in the bio-etanercept group was observed in 4 (5.1%; visit 6), 4 (5.0%; visit 9), and 3 (3.8%; visit 11) patients, and in 5 (6.4%), 5 (6.5%), and 3 (4.1%) patients in the O-etanercept group. The differences between the 2 groups were not significant (Pâ >â .99). CONCLUSIONS: This study showed that bio-etanercept was equivalent to the reference formulation.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Etanercept , Humans , Etanercept/therapeutic use , Etanercept/adverse effects , Etanercept/administration & dosage , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Female , Male , Middle Aged , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage , Adult , Treatment Outcome , Aged , Therapeutic EquivalencyABSTRACT
INTRODUCTION: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha, and GP1111 (Zessly®, Sandoz) is the most recently approved infliximab biosimilar in Europe. We reviewed the approval process and key evidence for GP1111, focusing primarily on the indications of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). AREAS COVERED: This narrative review discusses preclinical, clinical, and real-world data for GP1111. EXPERT OPINION: Results from the Phase III REFLECTIONS trial in patients with moderate-to-severe active RA despite methotrexate therapy confirmed the similarity in efficacy and safety between GP1111 and reference infliximab. Switching from reference infliximab to GP1111 in REFLECTIONS had no impact on efficacy or safety. Since the European approval of GP1111 in March 2018, real-world data have also confirmed the efficacy and safety of switching from another infliximab biosimilar to GP1111 in patients with RA and IBD. In addition, budget impact analysis of various sequential targeted treatments in patients with RA found that GP1111 was cost-effective when used early after failure of conventional synthetic disease-modifying antirheumatic drugs. Therefore, 5 years' post-approval experience with GP1111 in RA and IBD, and key clinical and real-world evidence, support the safety and efficacy of continued use of GP1111 in all infliximab-approved indications.
Subject(s)
Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Infliximab , Humans , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Infliximab/therapeutic use , Infliximab/adverse effects , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Inflammatory Bowel Diseases/drug therapy , Drug Approval , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effectsABSTRACT
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.
Subject(s)
Biosimilar Pharmaceuticals , Drug Substitution , Gastrointestinal Agents , Inflammatory Bowel Diseases , Infliximab , Humans , Infliximab/adverse effects , Infliximab/therapeutic use , Infliximab/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/economics , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , Gastrointestinal Agents/adverse effects , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/administration & dosage , Treatment OutcomeABSTRACT
AVT04 (Uzpruvo®) is a biosimilar of the reference anti-interleukin (IL)-12 and IL-23 monoclonal antibody ustekinumab. It is approved in the EU for plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis and Crohn's disease as per the reference product. AVT04 has similar physicochemical characteristics to those of reference ustekinumab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate to severe chronic plaque psoriasis. AVT04 demonstrated clinical efficacy similar to that of reference ustekinumab in patients with moderate to severe chronic plaque psoriasis, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of AVT04 were similar to those of reference ustekinumab, and switching from reference ustekinumab to AVT04 had no impact on efficacy, safety or immunogenicity. The role of reference ustekinumab in the management of inflammatory diseases is well established and AVT04 provides an effective biosimilar alternative for patients requiring ustekinumab therapy.
Subject(s)
Biosimilar Pharmaceuticals , Psoriasis , Ustekinumab , Humans , Ustekinumab/therapeutic use , Ustekinumab/pharmacokinetics , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/pharmacology , Psoriasis/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal, Humanized/adverse effects , Dermatologic Agents/therapeutic use , Dermatologic Agents/pharmacokinetics , Dermatologic Agents/adverse effects , Dermatologic Agents/pharmacology , Crohn Disease/drug therapyABSTRACT
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.
Subject(s)
Biosimilar Pharmaceuticals , Lupus Erythematosus, Systemic , Rituximab , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/diagnosis , Rituximab/adverse effects , Rituximab/administration & dosage , Rituximab/therapeutic use , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/therapeutic use , Retrospective Studies , Female , Male , Adult , Middle Aged , Treatment Outcome , Drug Substitution , Antibodies, Monoclonal, Murine-DerivedABSTRACT
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.
Subject(s)
Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Visual Acuity , Humans , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Male , Female , Aged , Visual Acuity/drug effects , Treatment Outcome , Macular Degeneration/drug therapy , Middle Aged , Double-Blind Method , Aged, 80 and over , Choroidal Neovascularization/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/administration & dosageABSTRACT
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.
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.
Subject(s)
Antibodies, Monoclonal, Humanized , Biosimilar Pharmaceuticals , Syringes , Humans , Male , Adult , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Female , Middle Aged , Young Adult , Area Under Curve , Self Administration/instrumentation , Therapeutic EquivalencyABSTRACT
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.
Subject(s)
Adalimumab , Antirheumatic Agents , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Registries , Humans , Adalimumab/administration & dosage , Adalimumab/therapeutic use , Adalimumab/adverse effects , Female , Middle Aged , Male , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Aged , Spain , Retrospective Studies , Treatment Outcome , Drug Substitution/statistics & numerical data , AdultABSTRACT
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.
Subject(s)
Biosimilar Pharmaceuticals , Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/pharmacology , Receptor, ErbB-2/metabolism , Adult , Double-Blind Method , Trastuzumab/administration & dosage , Trastuzumab/therapeutic use , Trastuzumab/adverse effects , Aged , Young Adult , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Adolescent , Docetaxel/therapeutic use , Docetaxel/administration & dosage , Docetaxel/adverse effects , Neoplasm Metastasis , India , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND: For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator. METHODS: This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners. FINDINGS: There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38). INTERPRETATION: In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching. FUNDING: British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.
Subject(s)
Antirheumatic Agents , Arthritis, Juvenile , Biosimilar Pharmaceuticals , Drug Substitution , Humans , Arthritis, Juvenile/drug therapy , Male , Female , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/economics , Biosimilar Pharmaceuticals/adverse effects , Child , Adolescent , Antirheumatic Agents/therapeutic use , United Kingdom , Cohort Studies , Treatment Outcome , Child, Preschool , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Infliximab/therapeutic use , Adalimumab/therapeutic use , Etanercept/therapeutic use , Biological Products/therapeutic useABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Lymphoma, Large B-Cell, Diffuse , Prednisone , Rituximab , Vincristine , Humans , Rituximab/therapeutic use , Rituximab/adverse effects , Rituximab/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Female , Middle Aged , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Doxorubicin/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/adverse effects , Cyclophosphamide/administration & dosage , Aged , Prednisone/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , Vincristine/therapeutic use , Vincristine/adverse effects , Vincristine/administration & dosage , Adult , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/administration & dosage , Treatment Outcome , Aged, 80 and overABSTRACT
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.
Subject(s)
Biosimilar Pharmaceuticals , Pemphigus , Rituximab , Humans , Rituximab/adverse effects , Rituximab/therapeutic use , Rituximab/administration & dosage , Pemphigus/drug therapy , Pemphigus/immunology , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/administration & dosage , Biosimilar Pharmaceuticals/economics , Male , Female , Middle Aged , Adult , Treatment Outcome , Aged , Immunologic Factors/therapeutic use , Immunologic Factors/adverse effects , Immunologic Factors/administration & dosage , Remission Induction/methods , Retrospective StudiesSubject(s)
Adalimumab , Axial Spondyloarthritis , Biosimilar Pharmaceuticals , Humans , Adalimumab/therapeutic use , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Retrospective Studies , China/epidemiology , Female , Male , Treatment Outcome , Adult , Axial Spondyloarthritis/diagnosis , Axial Spondyloarthritis/immunology , Axial Spondyloarthritis/drug therapy , Antirheumatic Agents/therapeutic use , Middle Aged , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/adverse effectsABSTRACT
Importance: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars. Observations: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems. Conclusions and Relevance: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.
Subject(s)
Biosimilar Pharmaceuticals , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/economics , Biosimilar Pharmaceuticals/adverse effects , Humans , United States , Medical Oncology , Neoplasms/drug therapy , Neoplasms/psychology , Drug Costs , United States Food and Drug Administration , Drug Approval , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/economics , Antineoplastic Agents/adverse effectsABSTRACT
INTRODUCTION: Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events. AREAS COVERED: In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies. EXPERT OPINION: DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Randomized Controlled Trials as Topic , Humans , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage , Biological Products/adverse effects , Biological Products/administration & dosage , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/administration & dosage , Dose-Response Relationship, DrugABSTRACT
BACKGROUND: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). OBJECTIVE: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. RESEARCH DESIGN AND METHODS: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. RESULTS: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors. CONCLUSIONS: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.
Subject(s)
Arthritis, Psoriatic , Biological Products , Databases, Factual , Drug Substitution , Psoriasis , Humans , Arthritis, Psoriatic/drug therapy , Male , Female , Psoriasis/drug therapy , Middle Aged , Retrospective Studies , Adult , Biological Products/therapeutic use , Biological Products/adverse effects , Italy/epidemiology , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effectsABSTRACT
OBJECTIVE: VOLTAIRE-HCLF compared the relative bioavailability of citrate-free high-concentration and reference formulations of the biosimilar adalimumab-adbm (Cyltezo®), including pharmacokinetic (PK) profiles, immunogenicity, and safety profiles in healthy volunteers. METHODS: Healthy volunteers (N = 200) aged 18-55 years and with body mass index of 18.5-29.9 kg/m2 and no prior exposure to adalimumab were randomized in a 1:1 ratio to receive a single subcutaneous injection of either adalimumab-adbm 40 mg/0.4 mL (high-concentration formulation) or 40 mg/0.8 mL (reference formulation). Participants completed 13 follow-up visits over 57 days, followed by a safety follow-up period of up to 70 days. RESULTS: The main PK parameters were similar for the high-concentration and reference groups. For all primary endpoints, the geometric mean ratios and 90% confidence intervals of AUC0-1344, AUC0-∞, and Cmax for both groups were entirely within the standard 80-125% bioequivalence acceptance range at 101.88% (93.31-111.23%), 105.38% (95.06-116.81%), and 91.29% (84.38-98.76%), respectively. There were no differences in the proportion of anti-drug antibody-positive participants or in the distribution of anti-drug antibody titers between the two formulations at any time point after drug dosing. Participants who were given the high-concentration formulation of adalimumab-adbm experienced a lower incidence of adverse events and local reactions than those who were given the reference formulation. CONCLUSIONS: Overall, the high-concentration and reference adalimumab-adbm formulations had highly similar PK and immunogenicity profiles and were safe and well tolerated. CLINICAL TRIAL REGISTRATION: NCT05203289.