Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial

Astrid M. van Huizen; Gayle E. van der Kraaij; Celine I. Busard; Wouter Ouwerkerk; Juul M.P.A. van den Reek; Stef P. Menting; Errol P. Prens; Theo Rispens; Annick de Vries; Elke M.G.J. de Jong; Jo Lambert; Martijn B.A. van Doorn; Phyllis I. Spuls

doi:10.1111/jdv.19089

Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial

Astrid M. van Huizen^*
, Gayle E. van der Kraaij
, Celine I. Busard
, Wouter Ouwerkerk
, Juul M.P.A. van den Reek
, Stef P. Menting
, Errol P. Prens
, Theo Rispens
, Annick de Vries
, Elke M.G.J. de Jong
, Jo Lambert
, Martijn B.A. van Doorn
, Phyllis I. Spuls

^*Corresponding author for this work

Dermatology

University of Amsterdam
Amsterdam UMC
National Heart Centre Singapore
Radboud University Medical Center
Sanquin Blood Supply Foundation
Ghent University Hospital
Onze Lieve Vrouwe Gasthuis
Center for Human Drug Research

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

202 Downloads (Pure)

Abstract

Background: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. Objectives: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. Methods: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. Results: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. Conclusions: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.

Original language	English
Pages (from-to)	1815-1824
Number of pages	10
Journal	Journal of the European Academy of Dermatology and Venereology
Volume	37
Issue number	9
Early online date	4 Apr 2023
DOIs	https://doi.org/10.1111/jdv.19089
Publication status	Published - Sept 2023

Bibliographical note

Funding Information:
We thank S. Atalay, M. van Burken, N. Maes, R. Soenen, L. Prens, M. Tjong Joe Wai, F.M. Vermeulen, L. van Vugt for support in data collection, G.A. Appel, M. Kooijman-Otero, N. Pouw, H.M. van der Stok for monitoring this study and B. van Montfrans, S.W. Tas, A.H. Zwinderman for participating in data safety monitoring board.

Publisher Copyright:
© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

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Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasisFinal published version, 621 KBLicence: CC BY-NC

Cite this

van Huizen, A. M., van der Kraaij, G. E., Busard, C. I., Ouwerkerk, W., van den Reek, J. M. P. A., Menting, S. P., Prens, E. P., Rispens, T., de Vries, A., de Jong, E. M. G. J., Lambert, J., van Doorn, M. B. A., & Spuls, P. I. (2023). Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial. Journal of the European Academy of Dermatology and Venereology, 37(9), 1815-1824. https://doi.org/10.1111/jdv.19089

@article{22e27fd2be814892b5a422c5e8733472,

title = "Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial",

abstract = "Background: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. Objectives: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. Methods: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. Results: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8\% vs. 41.4\%; p = 0.326, week 145: 51.6\% vs. 41.4\%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. Conclusions: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.",

author = "\{van Huizen\}, \{Astrid M.\} and \{van der Kraaij\}, \{Gayle E.\} and Busard, \{Celine I.\} and Wouter Ouwerkerk and \{van den Reek\}, \{Juul M.P.A.\} and Menting, \{Stef P.\} and Prens, \{Errol P.\} and Theo Rispens and \{de Vries\}, Annick and \{de Jong\}, \{Elke M.G.J.\} and Jo Lambert and \{van Doorn\}, \{Martijn B.A.\} and Spuls, \{Phyllis I.\}",

note = "Funding Information: We thank S. Atalay, M. van Burken, N. Maes, R. Soenen, L. Prens, M. Tjong Joe Wai, F.M. Vermeulen, L. van Vugt for support in data collection, G.A. Appel, M. Kooijman-Otero, N. Pouw, H.M. van der Stok for monitoring this study and B. van Montfrans, S.W. Tas, A.H. Zwinderman for participating in data safety monitoring board. Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley \& Sons Ltd on behalf of European Academy of Dermatology and Venereology.",

year = "2023",

month = sep,

doi = "10.1111/jdv.19089",

language = "English",

volume = "37",

pages = "1815--1824",

journal = "Journal of the European Academy of Dermatology and Venereology",

issn = "0926-9959",

publisher = "John Wiley \& Sons Inc.",

number = "9",

}

van Huizen, AM, van der Kraaij, GE, Busard, CI, Ouwerkerk, W, van den Reek, JMPA, Menting, SP, Prens, EP, Rispens, T, de Vries, A, de Jong, EMGJ, Lambert, J, van Doorn, MBA & Spuls, PI 2023, 'Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial', Journal of the European Academy of Dermatology and Venereology, vol. 37, no. 9, pp. 1815-1824. https://doi.org/10.1111/jdv.19089

Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial. / van Huizen, Astrid M.; van der Kraaij, Gayle E.; Busard, Celine I. et al.
In: Journal of the European Academy of Dermatology and Venereology, Vol. 37, No. 9, 09.2023, p. 1815-1824.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis

T2 - Three-year follow-up data of a single-blind randomized controlled trial

AU - van Huizen, Astrid M.

AU - van der Kraaij, Gayle E.

AU - Busard, Celine I.

AU - Ouwerkerk, Wouter

AU - van den Reek, Juul M.P.A.

AU - Menting, Stef P.

AU - Prens, Errol P.

AU - Rispens, Theo

AU - de Vries, Annick

AU - de Jong, Elke M.G.J.

AU - Lambert, Jo

AU - van Doorn, Martijn B.A.

AU - Spuls, Phyllis I.

N1 - Funding Information: We thank S. Atalay, M. van Burken, N. Maes, R. Soenen, L. Prens, M. Tjong Joe Wai, F.M. Vermeulen, L. van Vugt for support in data collection, G.A. Appel, M. Kooijman-Otero, N. Pouw, H.M. van der Stok for monitoring this study and B. van Montfrans, S.W. Tas, A.H. Zwinderman for participating in data safety monitoring board. Publisher Copyright: © 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

PY - 2023/9

Y1 - 2023/9

N2 - Background: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. Objectives: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. Methods: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. Results: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. Conclusions: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.

AB - Background: Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied. Objectives: To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis. Methods: We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses. Results: Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group. Conclusions: In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.

UR - https://www.scopus.com/pages/publications/85153219474

U2 - 10.1111/jdv.19089

DO - 10.1111/jdv.19089

M3 - Article

C2 - 37014287

AN - SCOPUS:85153219474

SN - 0926-9959

VL - 37

SP - 1815

EP - 1824

JO - Journal of the European Academy of Dermatology and Venereology

JF - Journal of the European Academy of Dermatology and Venereology

IS - 9

ER -

van Huizen AM, van der Kraaij GE, Busard CI, Ouwerkerk W, van den Reek JMPA, Menting SP et al. Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial. Journal of the European Academy of Dermatology and Venereology. 2023 Sept;37(9):1815-1824. Epub 2023 Apr 4. doi: 10.1111/jdv.19089

Adalimumab combined with methotrexate versus adalimumab monotherapy in psoriasis: Three-year follow-up data of a single-blind randomized controlled trial

Abstract

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