Bimekizumab versus Secukinumab in Plaque Psoriasis.

Adult Anti-Inflammatory Agents / administration & dosage Antibodies, Monoclonal, Humanized / administration & dosage Candidiasis, Oral / etiology Double-Blind Method Drug Administration Schedule Female Humans Injections, Subcutaneous Intention to Treat Analysis Interleukin-17 / antagonists & inhibitors Male Middle Aged Psoriasis / drug therapy Severity of Illness Index

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
08 07 2021
Historique:
pubmed: 24 4 2021
medline: 21 7 2021
entrez: 23 4 2021
Statut: ppublish

Résumé

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined. In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority. A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%). In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).

Sections du résumé

BACKGROUND
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
METHODS
In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority.
RESULTS
A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%).
CONCLUSIONS
In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).

Identifiants

DOI: 10.1056/NEJMoa2102383 PMID: 33891380
pubmed: 33891380
doi: 10.1056/NEJMoa2102383
doi:

Substances chimiques

Anti-Inflammatory Agents 0
Antibodies, Monoclonal, Humanized 0
IL17F protein, human 0
Interleukin-17 0
bimekizumab 09495UIM6V
secukinumab DLG4EML025

Banques de données

ClinicalTrials.gov
['NCT03536884']

Types de publication

Clinical Trial, Phase III Comparative Study Equivalence Trial Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

142-152

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Kristian Reich (K)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Richard B Warren (RB)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Mark Lebwohl (M)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Melinda Gooderham (M)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Bruce Strober (B)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Richard G Langley (RG)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Carle Paul (C)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Dirk De Cuyper (D)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Veerle Vanvoorden (V)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Cynthia Madden (C)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Christopher Cioffi (C)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Luke Peterson (L)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

Andrew Blauvelt (A)

From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-inflammatoires › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Maladies du système stomatognathique › Maladies de la bouche › Candidose buccale › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Calendrier d'administration des médicaments › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Injections › Injections sous-cutanées › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Analyse en intention de traitement › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-17 › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Dermatoses papulosquameuses › Psoriasis › Bimekizumab versus Secukinumab in Plaque Psoriasis.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › Bimekizumab versus Secukinumab in Plaque Psoriasis.