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JAMA Dec 2019
Topics: Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antirheumatic Agents; Biosimilar Pharmaceuticals; Drug Costs; Heterocyclic Compounds, 3-Ring; Humans; Patents as Topic; Time Factors; United States
PubMed: 31644784
DOI: 10.1001/jama.2019.16275 -
Drugs in R&D Dec 2023Adalimumab-aqvh/CHS-1420 (YUSIMRY) (hereafter referred to as adalimumab-aqvh) was recently approved by the US Food and Drug Administration as a biosimilar for adalimumab.
BACKGROUND
Adalimumab-aqvh/CHS-1420 (YUSIMRY) (hereafter referred to as adalimumab-aqvh) was recently approved by the US Food and Drug Administration as a biosimilar for adalimumab.
OBJECTIVE
The current study was conducted to investigate the analytical similarity of adalimumab-aqvh and the reference product, adalimumab.
METHODS
The structural, functional, and stability attributes of adalimumab-aqvh and adalimumab were compared using state-of-the-art assays. The primary structure, disulfide structure, glycan profile, secondary and tertiary structures, molar mass, size variants, free thiol, charge variants, hydrophobic variants, post-translational modifications, subvisible particles, host cell proteins, and protein concentration were investigated. The functional similarity between adalimumab-aqvh and adalimumab was demonstrated by comparing fragment antigen-binding (Fab)-associated and fragment crystallizable (Fc)-associated biological activities. The stability of adalimumab-aqvh and of adalimumab was compared through forced degradation.
RESULTS
The structural attributes of adalimumab-aqvh were identical to those of adalimumab or met the similarity criteria, with a few exceptions. Adalimumab-aqvh and adalimumab exhibited comparable stability profiles and functional activities. Any observed differences in the physiochemical attributes did not impact the conclusion of similarity because they did not influence any functional activities related to the adalimumab mechanism of action.
CONCLUSION
The structural, functional, and stability data provide convincing evidence of biosimilarity between adalimumab-aqvh and the reference product, adalimumab.
Topics: Humans; Adalimumab; Biosimilar Pharmaceuticals
PubMed: 37632627
DOI: 10.1007/s40268-023-00437-3 -
Arthritis Research & Therapy Oct 2022We compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood...
OBJECTIVES
We compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood immunophenotyping to elucidate the immunological background and analyzed the impact of therapeutic drugs to verify the validity of immunological phenotypes as therapeutic targets.
METHODS
Patients were treated with guselkumab 100 mg (guselkumab group; n = 12) and adalimumab 40 mg (adalimumab group; n = 13). Arthritis disease activity, skin lesion activity, and patient-reported outcomes (PROs) were evaluated and compared between the two groups. The retention rate and adverse events were evaluated. Comprehensive phenotyping of peripheral immune cells was performed in both groups, and phenotypes were compared before and after treatment.
RESULTS
At 6 months, both groups showed significant improvement in arthritis disease activity and PROs. In the guselkumab group, skin symptoms significantly improved. The 6-month continuation rates were 91.7% (11/12) and 69.2% (9/13) in the guselkumab and adalimumab groups, respectively. Adverse events occurred in 2/12 and 5/13 patients in the guselkumab (16.7%) and adalimumab (38.5%) groups, respectively. Peripheral blood immunophenotyping showed that the proportion of activated T helper (Th) 1 cells was significantly lower in patients with PAO than in healthy controls and that the proportion of activated Th17 cells was significantly higher in patients with PAO, which significantly decreased after treatment with guselkumab.
CONCLUSION
Although guselkumab and adalimumab have comparable efficacy for PAO, their impact on immunophenotypes varies.
Topics: Humans; Adalimumab; Osteitis; Psoriasis; Immunophenotyping; Arthritis
PubMed: 36303202
DOI: 10.1186/s13075-022-02934-3 -
Nature Communications Jun 2023Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this... (Randomized Controlled Trial)
Randomized Controlled Trial
Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is -7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is -0.8 letters (95% CI, -6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.
Topics: Humans; Immunosuppressive Agents; Uveomeningoencephalitic Syndrome; Adalimumab; Cyclosporine; Biological Products
PubMed: 37355662
DOI: 10.1038/s41467-023-39483-5 -
Journal of Crohn's & Colitis Oct 2016Adalimumab is well-established therapy for adults with Crohn's disease [CD]. The aim of the study was to systematically assess the published evidence on the efficacy and... (Review)
Review
BACKGROUND AND AIM
Adalimumab is well-established therapy for adults with Crohn's disease [CD]. The aim of the study was to systematically assess the published evidence on the efficacy and safety of adalimumab for Crohn's disease in children.
METHODS
MEDLINE, EMBASE, the Cochrane Library, and abstracts from the main gastroenterological meetings in the past 5 years were systematically searched up to July 2015 for randomised controlled trials and observational studies on the efficacy and safety of adalimumab for Crohn's treatment in children and adolescents.
RESULTS
A total of 14 studies [1 randomised controlled trial, 13 case series], altogether including 664 patients [age: 1.9 to 21 years] were available for analysis. The studies differed with respect to patients' characteristics, including percentage of infliximab-naïve patients, disease duration, site of the disease, adalimumab doses, treatment duration, and follow-up period. The pooled remission rates were: 30% [n = 93/309] at 4 weeks, 54% [n = 79/145] at 3 months, 45% [n = 18/40] at 4 months, 42% [n = 146/345] at 6 months, 57% [n = 20/35] at 8 months, and 44% [n = 169/383] at 12 months. Of the total patients, 6% [n = 13/207] were classified as primary non-responders and 12% [n = 69/599] had severe adverse events reported including 2 deaths and 1 medulloblastoma. Withdrawal rate due to adverse events reported in one study was 35% [n = 64/182].
CONCLUSION
According to low-quality evidence based mainly on case series, approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile. There is still a need for high-quality evidence on effectiveness and safety of adalimumab for paediatric Crohn's disease.
Topics: Adalimumab; Adolescent; Child; Crohn Disease; Drug Administration Schedule; Humans; Immunosuppressive Agents; Induction Chemotherapy; Treatment Outcome
PubMed: 26995184
DOI: 10.1093/ecco-jcc/jjw077 -
Current Rheumatology Reports Aug 2018Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the... (Review)
Review
PURPOSE OF REVIEW
Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the evidence from bio-originator trials in rheumatoid arthritis (RA) to provide context for a critical review of biosimilar trial data.
RECENT FINDINGS
Currently, three adalimumab biosimilars are approved in Europe and/or the USA: Amgen's ABP 501 (AMJEVITA/Solymbic), Boehringer Ingelheim's BI 695501 (Cyltezo) and Samsung Bioepis's SB5 (Imraldi). All three agents met their pre-specified equivalence criteria. Subtle differences in adverse events and clinical responses between the reference and biosimilar products were noted. The introduction of adalimumab biosimilars will offer exciting opportunities in improving treatment access and increasing treatment options for RA and other licensed indications. Real-world data will further provide assurances on efficacy as well as safety.
Topics: Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Humans; Treatment Outcome
PubMed: 30094742
DOI: 10.1007/s11926-018-0769-6 -
Immunologic Research Feb 2017About a third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. Anti-adalimumab antibodies are associated with... (Review)
Review
About a third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. Anti-adalimumab antibodies are associated with reduced drug levels, loss of drug efficacy, clinical non-response and an increased risk of adverse effects. In case of suspected drug failure and in order to better define clinical efficacy, adalimumab as well as anti-adalimumab antibodies levels should be monitored. Sandwich or indirect enzyme-linked immunoassay is most commonly used for determining adalimumab, while bridging ELISA and antigen-binding test are most useful for determining anti-adalimumab antibodies. Most current assays cannot detect antibodies complexed with the adalimumab; however, methods for dissociation of the complexes using acid/temperature have been developed. The aim of this review is to report on the latest methodology for detecting adalimumab and anti-ADL antibodies, benefits of their detections in clinical practice, as well as expose problematic issues, such as different analytical sensitivity and specificity, standardization and validation. The main problem in measuring adalimumab or anti-ADL antibodies is high drug sensitivity, which can result in false-negative anti-ADL antibodies. Therefore, drug-tolerant assays have been developed. Cell-based assays, such as the reporter gene assay, are recommended for detection of functionally active adalimumab and their neutralizing anti-ADL antibodies.
Topics: Adalimumab; Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunoassay
PubMed: 27421721
DOI: 10.1007/s12026-016-8824-8 -
Expert Opinion on Drug Safety Jun 2020Childhood rheumatic diseases (CRD) are chronic inflammatory conditions, often leading to severe functional impairment and disability. They produce high direct and... (Review)
Review
INTRODUCTION
Childhood rheumatic diseases (CRD) are chronic inflammatory conditions, often leading to severe functional impairment and disability. They produce high direct and indirect costs for patients, their families and society overall. Biologic treatment, adalimumab of note, has drastically changed the disease management, significantly decreasing morbidity, over childhood, and eventually lifelong. After 12 years of pediatric experience with adalimumab, safety data resulted of great interest.
AREAS COVERED
This review summarizes published knowledge about safety of adalimumab in clinical trials and real-life setting studies. Infections and site injection reactions are considered the most frequent adverse events, but the occurrence of second autoimmune diseases as well as malignancy development are the two major concerns of the medical community and families.
EXPERT OPINION
Adalimumab has revolutionized treatment and prognosis of most of CRD, resulting in good outcomes with highly acceptable safety profile. Number and type of entered adverse events differ from clinical trials and registries, these latter mirroring clinical real life. Different temporal observations and sample cohorts mainly account of this discrepancy. Both randomized clinical trials and real-world data are complementary. Clinical trials coupled with long-term registries will help to improve the evidence-based safety for children with CRD.
Topics: Adalimumab; Animals; Antirheumatic Agents; Child; Humans; Injection Site Reaction; Randomized Controlled Trials as Topic; Registries; Rheumatic Diseases
PubMed: 32406768
DOI: 10.1080/14740338.2020.1763300 -
Gastroenterology Apr 2016
Topics: Adalimumab; Anti-Inflammatory Agents; Colitis, Ulcerative; Humans; Intestinal Mucosa; Patient Outcome Assessment; Wound Healing
PubMed: 26926449
DOI: 10.1053/j.gastro.2016.02.055 -
BioDrugs : Clinical Immunotherapeutics,... Apr 2017Adalimumab (Humira) is a tumour necrosis factor (TNF)-α inhibitor available in various countries worldwide, including the USA, Japan and those of the EU, for the... (Review)
Review
Adalimumab (Humira) is a tumour necrosis factor (TNF)-α inhibitor available in various countries worldwide, including the USA, Japan and those of the EU, for the treatment of non-infectious intermediate, posterior and panuveitis in adults. It is the first biological agent approved for this indication. In two multinational, phase III studies in adults with active and inactive disease, subcutaneous adalimumab significantly reduced the risk of treatment failure relative to placebo following the tapered withdrawal of corticosteroid therapy. Significant differences favouring adalimumab over placebo were seen for each component of treatment failure (vitreous haze, new active inflammatory lesions, anterior chamber cell grade and a worsening of best-corrected visual acuity) in patients with active disease and for the visual acuity component in patients with inactive disease. Adalimumab was also significantly more effective than placebo in improving multiple aspects of uveitic inflammation in patients with active, but not in those with inactive, disease. Adalimumab was generally well tolerated in these patient populations. Its tolerability profile was consistent with the known tolerability profile of the agent in other indications and no new safety signals were identified. Moreover, the incidence of anti-adalimumab antibodies was low. Thus, adalimumab is an effective and generally well tolerated treatment option in adults with non-infectious intermediate, posterior and panuveitis, including those who cannot be treated with corticosteroids.
Topics: Adalimumab; Anti-Inflammatory Agents, Non-Steroidal; Humans; Uveitis
PubMed: 28229433
DOI: 10.1007/s40259-017-0213-x