Continued treatment with secukinumab is associated with high retention or regain of response

M. Augustin; D. Thaci; K. Eyerich; A. Pinter; M. Radtke; F. Lauffer; U. Mrowietz; S. Gerdes; D. Pariser; M. Lebwohl; C. Sieder; N. Melzer; K. Reich

doi:10.1111/bjd.17991

Continued treatment with secukinumab is associated with high retention or regain of response

M. Augustin^*, D. Thaci, K. Eyerich, A. Pinter, M. Radtke, F. Lauffer, U. Mrowietz, S. Gerdes, D. Pariser, M. Lebwohl, C. Sieder, N. Melzer, K. Reich

^*Corresponding author for this work

11 Citations (Scopus)

Abstract

Background: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. Objectives: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. Methods: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) (‘excellent’), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 (‘good’) and < PASI 75 (‘insufficient’). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in ‘insufficient’ response. All comparisons are descriptive. Results: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. Conclusions: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic?. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add?. To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.

Original language	English
Journal	British Journal of Dermatology
Volume	182
Issue number	1
Pages (from-to)	67-75
Number of pages	9
ISSN	0007-0963
DOIs	https://doi.org/10.1111/bjd.17991
Publication status	Published - 01.01.2020

Funding

This analysis was funded by Novartis Pharma GmbH, Nuremberg, Germany and conducted by Winicker Norimed, Nuremberg, Germany. The authors thank Evelyn Altemeyer of Novartis Ireland Ltd for providing medical writing support/ editorial support, which was funded by Novartis Pharma GmbH, Nuremberg, Germany in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/ gpp3). Conflicts of interest: M.A. has served as consultant to or paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Cel-gene, Centocor, Eli Lilly, GSK, Janssen-Cilag, LEO, Medac, Merck, MSD, Novartis, Pfizer, UCB and Xenoport. D.T. has received research support/principal investigator (clinical trials) from AbbVie, Almiral, Amgen, Astellas, Biogen-Idec, Boehringer Ingelheim, Celgene, Dignity, Elli-Lilly, Forward Pharma, Glaxo-Smith-Kline, LEO, Janssen-Cilag, Maruho, MSD, Mit-subishi Pharma, Novartis, Pfizer, Roche and Sandoz, has acted as a consultant for AbbVie, Biogen-Idec, Celgene, Dignity, Maruho, Mitsubishi, Novartis, Pfizer, and Xenoport, has received honoraria from AbbVie, Biogen-Idec, Celgene,Jans-sen, LEO, Pfizer, Roche-Possay, Novartis and Mundipharma and has participated in scientific advisory boards for AbbVie, Amgen, Biogen-Idec, Celgene, Eli Lilly, GSK, Pfizer, Novartis, Janssen, Mundipharma and Sandoz. K.E. has received advisory board and speaker′s fees from AbbVie, Almirall, Berlin Che-mie, Celgene, LEO, Hexal, Janssen, Novartis and Lilly and research support from Novartis, Celgene, Galapagos, Mor-phosys and LEO. A.P. is a speaker for AbbVie, Allmirall-Hermal, Amgen, Biogen Idec, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Medac, Novartis, Pfizer and UCB Pharma, an advisor for AbbVie, Allmirall-Hermal, Amgen, Cel-gene, Eli Lilly, Janssen, LEO Pharma and Novartis and has participated in clinical trials funded by AbbVie, Allmirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Schering-Plough and UCB Pharma. M.R. has been invited for lectures by/received research funding from/was advisor for/conducted clinical studies and health services research for Abbott/AbbVie, Almirall, Amgen, Astellas, Biogen, Biologix, Bo€hringer, Cel-gene, Galderma, Hexal, Janssen-Cilag, La Roche Posay, LEO, Lilly Pharma, Medac, Merck, MSD, Mundipharma, Novartis, Pfizer, Sandoz, Sanofi and Takeda Pharmaceutical. F.L. received consultancy fees, speaker’s honoraria or travel support from: Novartis, Lilly, Sanofi, AbbVie, Janssen and Actelion. U.M. has acted as an investigator and/or consultant for Abbott/AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Dr Reddy’s, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, MSD, Miltenyi Biotech, Novartis, VBL and Xenoport. S.G. has been an advisor and/or received speakers’ honoraria and/or received grants and/or participated in clinical trials of the following companies: Abbott/AbbVie, Almirall-Hermal, Amgen, Baxalta, Bayer Health Care, Biogen Idec, Bioskin, Boehringer Ingelheim, Cel-gene, Centocor, Dermira, Eli Lilly, Foamix, Forward Pharma, Galderma, Hexal AG, Isotechnika, Janssen-Cilag, LEO Pharma, Medac, Merck Serono, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Polichem SA, Regeneron Pharmaceutical, Sandoz Biophar-maceuticals, Sanofi-Aventis, Schering-Plough, Takeda, Teva, UCB Pharma, VBL therapeutics and Wyeth Pharma. D.P. has served as consultant and/or principal investigator for Abbott Laboratories, Amgen, Asana Biosciences, Bickel Biotechnology, Biofrontera AG, Celgene Corporation, Dermavant Sciences, Dermira, DUSA Pharmaceuticals, Inc., Eli Lilly, LEO Pharma, Merck & Co., Novartis, Novo Nordisk, Ortho Dermatologics, Peplin, Pfizer, Photocure ASA, Promius Pharmaceuticals, Regeneron, Sanofi, Stiefel, TheraVida and Valeant Pharmaceuticals International. M.L. is an employee of Mount Sinai and receives research funds from: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Janssen/Johnson & Johnson, LEO Pharmaceutucals, Medimmune/Astra Zeneca, Novartis, Pfizer, Sciderm, Valeant, and ViDac and is also a consultant for Allergan, Aqua, Promius and LEO Pharma. C.S. and N.M. are employees of Novartis Pharma GmbH, Nuremberg, Germany. K.R. has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Cen-tocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO, Lilly, Medac, Merck Sharp & Dohme Corp., Novartis, Ocean Pharma, Pfizer, Regeneron, Sanofi, Takeda, UCB Pharma and Xenoport

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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10.1111/bjd.17991

Cite this

@article{9e848c16ff554b7495ff1b2551baab0e,

title = "Continued treatment with secukinumab is associated with high retention or regain of response",

abstract = "Background: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. Objectives: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. Methods: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90\% improvement in the Psoriasis Area and Severity Index (PASI 90) ({\textquoteleft}excellent{\textquoteright}), ≥ 75\% improvement in PASI (PASI 75) and < PASI 90 ({\textquoteleft}good{\textquoteright}) and < PASI 75 ({\textquoteleft}insufficient{\textquoteright}). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in {\textquoteleft}insufficient{\textquoteright} response. All comparisons are descriptive. Results: At 52 weeks, in CLEAR, 90·2\% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7\% (261/336) showed stable efficacy without any reduction of response [74·3\% (252/339) and 59·9\% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5\% (273/327) and 66·4\% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3\% (190/326) and 42·6\% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50\% (8/16) of patients in CLEAR and 26\% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. Conclusions: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic?. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add?. To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.",

author = "M. Augustin and D. Thaci and K. Eyerich and A. Pinter and M. Radtke and F. Lauffer and U. Mrowietz and S. Gerdes and D. Pariser and M. Lebwohl and C. Sieder and N. Melzer and K. Reich",

year = "2020",

month = jan,

day = "1",

doi = "10.1111/bjd.17991",

language = "English",

volume = "182",

pages = "67--75",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Oxford University Press",

number = "1",

}

TY - JOUR

T1 - Continued treatment with secukinumab is associated with high retention or regain of response

AU - Augustin, M.

AU - Thaci, D.

AU - Eyerich, K.

AU - Pinter, A.

AU - Radtke, M.

AU - Lauffer, F.

AU - Mrowietz, U.

AU - Gerdes, S.

AU - Pariser, D.

AU - Lebwohl, M.

AU - Sieder, C.

AU - Melzer, N.

AU - Reich, K.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. Objectives: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. Methods: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) (‘excellent’), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 (‘good’) and < PASI 75 (‘insufficient’). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in ‘insufficient’ response. All comparisons are descriptive. Results: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. Conclusions: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic?. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add?. To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.

AB - Background: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows sustained efficacy in moderate-to-severe psoriasis. Objectives: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. Methods: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) (‘excellent’), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 (‘good’) and < PASI 75 (‘insufficient’). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in ‘insufficient’ response. All comparisons are descriptive. Results: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. Conclusions: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic?. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, shows significant and sustained efficacy in the treatment of moderate-to-severe psoriasis. Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add?. To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories. Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon. Patient factors such as body weight may affect the likelihood of loss of efficacy.

UR - https://www.scopus.com/pages/publications/85069821395

U2 - 10.1111/bjd.17991

DO - 10.1111/bjd.17991

M3 - Journal articles

C2 - 30972746

AN - SCOPUS:85069821395

SN - 0007-0963

VL - 182

SP - 67

EP - 75

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 1

ER -

Continued treatment with secukinumab is associated with high retention or regain of response

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