- MeSH
- Spondylitis, Ankylosing drug therapy therapy MeSH
- Immunoglobulin G administration & dosage pharmacology therapeutic use MeSH
- Humans MeSH
- Evidence-Based Medicine MeSH
- Arthritis, Psoriatic drug therapy therapy MeSH
- Receptors, Tumor Necrosis Factor administration & dosage therapeutic use MeSH
- Arthritis, Rheumatoid drug therapy therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
- About
- Enbrel
Cílem této studie bylo identifikovat buněčnou populaci, kterou by bylo možné využít k předpovědi reakce na anti-TNF terapii. Celkem bylo analyzováno 46 pacientů, jimž byly podávány anti-TNF preparáty: 23 pacientů s juvenilní idiopatickou artritidou (11– Enbrel, 11– Remicade a 1– Humira), 16 pacientů s ankylozující spondylitidou (8 – Enbrel, 8 – Remicade), 5 pacientů s revmatoidní artritidou (všichni Enbrel) a 2 pacienti s psoriatickou artritidou (oba Enbrel) a dále 19 kontrol. U 11 pacientů s juvenilní idiopatickou artritidou a 3 pacientů s ankylozující spondylitidou byly k dispozici klinické parametry před začátkem biologické léčby a 3 měsíce po začátku (hladina CRP, rychlost sedimentace, DAS28, BASDAI, VAS skóre, počet citlivých a oteklých kloubů). K imunofenotypizaci mononukleárních buněk periferní krve pacientů a kontrol byla použita polychromatická průtoková cytometrie. Identifikovali jsme dvě skupiny pacientů, odpovídající na léčbu a rezistentní na léčbu, které se významně lišily frekvencí CD19+CD20-CD27highCD38+ CD138+ plazmatických buněk (odpovídající pacienti: 1,3-10,3 %; medián 7,04±1,05; 95 %CI 4,06–9,03 vs. rezistentní pacienti 17,3–37,3; medián 27,75±9,18; 95%CI 18,12–37,38; p=0,0007). U všech pacientů reagujících na léčbu byly všechny klinické parametry statisticky významně sníženy. Frekvence CD19+CD20- CD27highCD38+CD138+ plazmatických buněk byly u pacientů odpovídajících na léčbu nejméně 13x nižší než u rezistentních pacientů a tato populace by tak mohla představovat biologický marker predikující úspěšnost anti-TNF terapie.
The aim of the study was to identify cell population which could be used as a marker predicting response to anti-TNF therapy. A total of 46 patients was analyzed, out of them: 23 patients with juvenile idiopatic arthritis (11 – Enbrel, 11– Remicade and 1– Humira), 16 patients with ankylosing spondylitis (8 – Enbrel, 8 – Remicade), 5 patients with rheumatoid arthritis (all Enbrel) and 2 patients with psoriatic arthritis (both Enbrel) and 19 controls. Clinical parameters (CRP, ESR, DAS28, BASDAI, VAS score, number of tender and swollen joints) from 11 patients with juvenile idiopatic arthritis and 3 with ankylosing spondylitis were available before and 3 months after onset of the therapy. Immunophenotyping of peripheral blood of patients and controls was performed using polychromatic flow cytometry. A population of CD19+CD20-CD27highCD38+CD138+ plasma cells was identified which significantly differed in the frequencies between responding and resistent patients (responders: 1.3–10.3%; median 7.04±1.05; 95%CI 4.06–9.03 vs. non-responders 17.3–37.3; median 27.75±9.18; 95%CI 18.12–37.38; p=0.0007). All responders showed statistically significant improvement of clinical parameters. The frequency of CD19+CD20-CD27highCD38+ CD138+ plasma cell population was found to be in responders at least 13-fold reduced in comparison to non-responders and this population might represent biological marker predicting the outcome of anti-TNF therapy.
- Keywords
- Humira, Remicade, Enbrel,
- MeSH
- Biomarkers MeSH
- C-Reactive Protein analysis MeSH
- Antigens, CD blood MeSH
- Research Support as Topic MeSH
- Immunophenotyping methods MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Predictive Value of Tests MeSH
- Arthritis, Rheumatoid drug therapy blood MeSH
- Tumor Necrosis Factor-alpha antagonists & inhibitors MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
Neúčinnost „chorobu modifikujících“ farmak u části pacientů se zánětlivými artropatiemi a nepřesvědčivé výsledky studií sledujících radiologickou progresi urychlily snahu o vývoj nových, účinnějších farmak s cílem ovlivnit nejen klinickou aktivitu, ale i radiologickou progresi. Vývoj těchto nových farmak vychází ze znalostí klíčové role T- a B-lymfocytů a cytokinů produkovaných aktivovanými imunokompetentními buňkami v patogenezi zánětlivých artropatií. Mezi nejvýznamnější cytokiny patří faktor nekrotizující tumory (TNF?- „tumor necrosis factor ?“), interleukin-1 (IL-1) a interleukin-6 (IL-6). Tyto poznatky vedly k vývoji látek, specificky zaměřených na inhibici těchto buněk resp. jejich cytokinů, v prvé řadě TNF?. Léčba těmito farmaky se ukázala být vysoce účinnou u revmatoidní artritidy rezistentní na léčbu standardními „chorobu modifikujícími farmaky“ a to při sledování prakticky všech dostupných parametrů. Následovaly podobně dobré zkušenosti jsou i s léčbou spondylartritid, zejména psoriatické artritidy a ankylozující spondylitidy. V současné době jsou k dispozici 3 látky inhibující TNF?: infliximab (REMICADE), etanercept (ENBREL) a adalimumab (HUMIRA). Další výzkum na tomto poli vedl k vývoji farmak ovlivňujících aktivaci T-buněk na úrovni tzv. kostimulačních molekul (tzv. imunomodulátory, např. abatacept). Jiný přístup k „biologické léčbě“ představuje snaha ovlivnit aktivaci B-buněk, které rovněž hrají roli v genezi revmatoidní artritidy (rituximab).
The ineffectiveness of „disease-modifying“ drugs in a proportion of patients with inflammatory arthropathies and inconclusive results of studies investigating radiological progression have accelerated the efforts to develop new, more effective pharmaceuticals with an aim to affect not only clinical activity but also radiological progression. The development of these new pharmaceuticals is based on the knowledge of the key roles of T and B lymphocytes and cytokines produced by activated immunocompetent cells in the pathogenesis of inflammatory arthropathies. The most significant cytokines include tumor necrosis factor alpha (TNF?), interleukin-1 (IL-1), and interleukin-6 (IL-6). This knowledge has led to the development of substances specifically designed to inhibit these cells and/or their cytokines, primarily TNF?. Treatment with these pharmaceuticals has proved highly effective in rheumatoid arthritis resistant to treatment with standard „disease-modifying“ drugs in virtually all available parameters followed. Similarly positive experience has been gained with the treatment of spondylarthritides, particularly psoriatic arthritis and ankylosing spondylitis. Currently, three substances inhibiting TNF? are available: infliximab (REMICADE), etanercept (ENBREL), and adalimumab (HUMIRA). Further research in this field has led to the development of pharmaceuticals affecting T cell activation at the level of so-called costimulatory molecules (so-called immunomodulators such as abatacept). Another approach to „biological therapy“ is represented by an effort to affect activation of B cells that also play a role in the genesis of rheumatoid arthritis (rituximab).
- Keywords
- Fc-fusion protein, Remicade, Enbrel, Humira, Orencia,
- MeSH
- Abatacept MeSH
- Adalimumab MeSH
- Antirheumatic Agents pharmacology MeSH
- Biological Therapy methods trends MeSH
- Denosumab MeSH
- Etanercept MeSH
- Immunoglobulin G MeSH
- Immunoconjugates MeSH
- Infliximab MeSH
- Humans MeSH
- RANK Ligand MeSH
- Inflammation Mediators MeSH
- Antibodies, Monoclonal MeSH
- Receptors, Tumor Necrosis Factor MeSH
- Recombinant Fusion Proteins MeSH
- Rheumatic Diseases drug therapy MeSH
- Tumor Necrosis Factor-alpha drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Keywords
- Enbrel,
- MeSH
- beta-Thalassemia drug therapy complications therapy MeSH
- Etanercept MeSH
- Immunoglobulin E therapeutic use MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Psoriasis drug therapy complications therapy MeSH
- Tumor Necrosis Factor Decoy Receptors therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
BACKGROUND: EGALITY was a phase III confirmatory efficacy and safety study conducted in patients with plaque-type psoriasis as a part of totality of evidence gathered during the development of GP2015, an etanercept biosimilar. OBJECTIVE: To demonstrate equivalent efficacy and comparable safety and immunogenicity of GP2015 and the etanercept originator product (ETN, Enbrel® ) and evaluate effects of repeated switching between GP2015 and ETN. Results for efficacy, safety and immunogenicity during treatment period (TP) 2 (TP2) are presented pooling the two continued treatment arms (pooled continued) versus the two treatment arms with repeated switches (pooled switched). METHODS: Patients (n = 531) were randomized 1:1 to self-administer GP2015 or ETN twice-weekly subcutaneously during TP1. Patients with a ≥50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were re-randomized for TP2 to continue the same treatment at once-weekly dosing or to undergo three consecutive treatment switches between GP2015 and ETN until week 30. Patients continued the last-assigned treatment during TP2, until week 52. RESULTS: Mean (standard deviation [SD]) PASI scores at baseline were similar in patients who underwent multiple switches compared to those with continued treatments during TP2. During TP2, PASI 50, PASI 75 and PASI 90 response rates, percent change from baseline in PASI scores and all other efficacy parameters were similar between the pooled switched and pooled continued treatment groups at all time points. The incidence of treatment-emergent adverse events including injection site reactions was comparable between the pooled switched (36.7%) and pooled continued (34.9%) groups. None of the patients in either treatment group were positive for binding anti-drug antibodies in TP2. CONCLUSION: Treatment efficacy, safety and immunogenicity were similar between the pooled continued and pooled switched treatments during TP2, indicating that there are no effects in the short term on clinical data of multiple switches between GP2015 and ETN.
- MeSH
- Biosimilar Pharmaceuticals administration & dosage adverse effects therapeutic use MeSH
- Chronic Disease MeSH
- Dermatologic Agents administration & dosage adverse effects immunology therapeutic use MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Etanercept administration & dosage adverse effects analogs & derivatives therapeutic use MeSH
- Injections, Subcutaneous MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies immunology MeSH
- Psoriasis drug therapy immunology MeSH
- Drug Administration Schedule MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- MeSH
- Etanercept * MeSH
- Immunoglobulin G * MeSH
- Humans MeSH
- Arthritis, Rheumatoid drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
- Comment MeSH
- MeSH
- Biosimilar Pharmaceuticals * economics MeSH
- Etanercept economics MeSH
- Humans MeSH
- Arthritis, Rheumatoid drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
BACKGROUND: GP2015 is a proposed etanercept biosimilar. OBJECTIVES: To demonstrate equivalent efficacy, and comparable safety and immunogenicity of GP2015 and the etanercept originator (ETN, Enbrel® ) in patients with moderate-to-severe chronic plaque-type psoriasis. METHODS: In total, 531 eligible patients were randomized 1 : 1 to self-administer GP2015 or ETN twice weekly subcutaneously. Patients with ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were rerandomized to continue the same treatment on a once-weekly dosing schedule or to undergo a sequence of three treatment switches between GP2015 and ETN until week 30. Thereafter, patients continued treatment with the product they had been assigned to last, up to week 52. RESULTS: The difference in PASI 75 (75% improvement from baseline PASI score) response rates at week 12 between GP2015 and ETN (primary end point) was -2·3%. The 95% confidence interval (-9·85 to 5·30) was well contained within the prespecified margin range of -18 to 18. The incidence of treatment-emergent adverse events up to week 52 was comparable between continued GP2015 (59·8%) and ETN (57·3%); switching treatments revealed comparable safety profiles. Antidrug antibodies, all non-neutralizing, were limited to five patients on ETN during treatment period 1, and one patient in the switched ETN group, who had been treated with GP2015 for 12 weeks at the time of the finding. CONCLUSIONS: The EGALITY study demonstrated equivalent efficacy and comparable safety and immunogenicity of GP2015 and ETN. The study results provide the final clinical confirmation of biosimilarity and contribute to the totality of the evidence proposing that GP2015 is an etanercept biosimilar.
- MeSH
- Biosimilar Pharmaceuticals administration & dosage adverse effects pharmacokinetics MeSH
- Chronic Disease MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Etanercept administration & dosage adverse effects pharmacokinetics MeSH
- Injections, Subcutaneous MeSH
- Humans MeSH
- Drug Substitution MeSH
- Antibodies, Neutralizing metabolism MeSH
- Psoriasis drug therapy MeSH
- Drug Administration Schedule MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
