Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial

Mikkel Østergaard; Ronald F van Vollenhoven; Anna Rudin; Merete Lund Hetland; Marte Schrumpf Heiberg; Dan C Nordström; Michael T Nurmohamed; Bjorn Gudbjornsson; Lykke Midtbøll Ørnbjerg; Pernille Bøyesen; Kristina Lend; Kim Hørslev-Petersen; Till Uhlig; Tuulikki Sokka; Gerdur Grondal; Simon Krabbe; Joakim Lindqvist; Inger Gjertsson; Daniel Glinatsi; Meliha Crnkic Kapetanovic; Anna-Birgitte Aga; Francesca Faustini; Pinja Parmanne; Tove Lorenzen; Cagnotto Giovanni; Johan Back; Oliver Hendricks; Daisy Vedder; Tuomas Rannio; Emma Grenholm; Maud Kristine Ljoså; Eli Brodin; Hanne Lindegaard; Annika Söderbergh; Milad Rizk; Alf Kastbom; Per Larsson; Line Uhrenholt; Søren Andreas Just; David J Stevens; Trine Bay Laurbjerg; Gunnstein Bakland; Inge Christoffer Olsen; Espen A Haavardsholm; Jon Lampa; NORD-STAR study group

doi:10.1136/ard-2023-224116

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial

Mikkel Østergaard^*, Ronald F van Vollenhoven, Anna Rudin, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Bjorn Gudbjornsson, Lykke Midtbøll Ørnbjerg, Pernille Bøyesen, Kristina Lend, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka, Gerdur Grondal, Simon Krabbe, Joakim Lindqvist, Inger Gjertsson, Daniel Glinatsi, Meliha Crnkic KapetanovicAnna-Birgitte Aga, Francesca Faustini, Pinja Parmanne, Tove Lorenzen, Cagnotto Giovanni, Johan Back, Oliver Hendricks, Daisy Vedder, Tuomas Rannio, Emma Grenholm, Maud Kristine Ljoså, Eli Brodin, Hanne Lindegaard, Annika Söderbergh, Milad Rizk, Alf Kastbom, Per Larsson, Line Uhrenholt, Søren Andreas Just, David J Stevens, Trine Bay Laurbjerg, Gunnstein Bakland, Inge Christoffer Olsen, Espen A Haavardsholm, Jon Lampa, NORD-STAR study group

^*Corresponding author for this work

6 Citations (Scopus)

Abstract

BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.

METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025).

RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%.

CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.

TRIAL REGISTRATION NUMBER: NCT01491815.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	82
Issue number	10
Pages (from-to)	1286-1295
Number of pages	10
ISSN	0003-4967
DOIs	https://doi.org/10.1136/ard-2023-224116
Publication status	Published - Oct 2023

Keywords

Abatacept
Biological Therapy
Certolizumab pegol
Methotrexate
Rheumatoid Arthritis
Abatacept/therapeutic use
Humans
Treatment Outcome
Certolizumab Pegol/therapeutic use
Antirheumatic Agents/adverse effects
Arthritis, Rheumatoid/diagnostic imaging
Drug Therapy, Combination
Methotrexate/therapeutic use

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Østergaard, M., van Vollenhoven, R. F., Rudin, A., Hetland, M. L., Heiberg, M. S., Nordström, D. C., Nurmohamed, M. T., Gudbjornsson, B., Ørnbjerg, L. M., Bøyesen, P., Lend, K., Hørslev-Petersen, K., Uhlig, T., Sokka, T., Grondal, G., Krabbe, S., Lindqvist, J., Gjertsson, I., Glinatsi, D., ... NORD-STAR study group (2023). Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Annals of the Rheumatic Diseases, 82(10), 1286-1295. https://doi.org/10.1136/ard-2023-224116

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. / Østergaard, Mikkel; van Vollenhoven, Ronald F; Rudin, Anna et al.
In: Annals of the Rheumatic Diseases, Vol. 82, No. 10, 10.2023, p. 1286-1295.

Research output: Contribution to journal › Journal article › Research › peer-review

Østergaard, M, van Vollenhoven, RF, Rudin, A, Hetland, ML, Heiberg, MS, Nordström, DC, Nurmohamed, MT, Gudbjornsson, B, Ørnbjerg, LM, Bøyesen, P, Lend, K, Hørslev-Petersen, K, Uhlig, T, Sokka, T, Grondal, G, Krabbe, S, Lindqvist, J, Gjertsson, I, Glinatsi, D, Kapetanovic, MC, Aga, A-B, Faustini, F, Parmanne, P, Lorenzen, T, Giovanni, C, Back, J, Hendricks, O, Vedder, D, Rannio, T, Grenholm, E, Ljoså, MK, Brodin, E, Lindegaard, H, Söderbergh, A, Rizk, M, Kastbom, A, Larsson, P, Uhrenholt, L, Just, SA, Stevens, DJ, Bay Laurbjerg, T, Bakland, G, Olsen, IC, Haavardsholm, EA, Lampa, J & NORD-STAR study group 2023, 'Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial', Annals of the Rheumatic Diseases, vol. 82, no. 10, pp. 1286-1295. https://doi.org/10.1136/ard-2023-224116

Østergaard M, van Vollenhoven RF, Rudin A, Hetland ML, Heiberg MS, Nordström DC et al. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial. Annals of the Rheumatic Diseases. 2023 Oct;82(10):1286-1295. doi: 10.1136/ard-2023-224116

@article{497cf5754b8643319ff7621a9b900935,

title = "Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial",

abstract = "BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-na{\"i}ve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025).RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%.CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.TRIAL REGISTRATION NUMBER: NCT01491815.",

keywords = "Abatacept, Biological Therapy, Certolizumab pegol, Methotrexate, Rheumatoid Arthritis, Abatacept/therapeutic use, Humans, Treatment Outcome, Certolizumab Pegol/therapeutic use, Antirheumatic Agents/adverse effects, Arthritis, Rheumatoid/diagnostic imaging, Drug Therapy, Combination, Methotrexate/therapeutic use",

author = "Mikkel {\O}stergaard and {van Vollenhoven}, {Ronald F} and Anna Rudin and Hetland, {Merete Lund} and Heiberg, {Marte Schrumpf} and Nordstr{\"o}m, {Dan C} and Nurmohamed, {Michael T} and Bjorn Gudbjornsson and {\O}rnbjerg, {Lykke Midtb{\o}ll} and Pernille B{\o}yesen and Kristina Lend and Kim H{\o}rslev-Petersen and Till Uhlig and Tuulikki Sokka and Gerdur Grondal and Simon Krabbe and Joakim Lindqvist and Inger Gjertsson and Daniel Glinatsi and Kapetanovic, {Meliha Crnkic} and Anna-Birgitte Aga and Francesca Faustini and Pinja Parmanne and Tove Lorenzen and Cagnotto Giovanni and Johan Back and Oliver Hendricks and Daisy Vedder and Tuomas Rannio and Emma Grenholm and Ljos{\aa}, {Maud Kristine} and Eli Brodin and Hanne Lindegaard and Annika S{\"o}derbergh and Milad Rizk and Alf Kastbom and Per Larsson and Line Uhrenholt and Just, {S{\o}ren Andreas} and Stevens, {David J} and {Bay Laurbjerg}, Trine and Gunnstein Bakland and Olsen, {Inge Christoffer} and Haavardsholm, {Espen A} and Jon Lampa and {NORD-STAR study group}",

note = "COPECARE {\textcopyright} Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2023",

month = oct,

doi = "10.1136/ard-2023-224116",

language = "English",

volume = "82",

pages = "1286--1295",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "10",

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TY - JOUR

T1 - Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis

T2 - 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial

AU - Østergaard, Mikkel

AU - van Vollenhoven, Ronald F

AU - Rudin, Anna

AU - Hetland, Merete Lund

AU - Heiberg, Marte Schrumpf

AU - Nordström, Dan C

AU - Nurmohamed, Michael T

AU - Gudbjornsson, Bjorn

AU - Ørnbjerg, Lykke Midtbøll

AU - Bøyesen, Pernille

AU - Lend, Kristina

AU - Hørslev-Petersen, Kim

AU - Uhlig, Till

AU - Sokka, Tuulikki

AU - Grondal, Gerdur

AU - Krabbe, Simon

AU - Lindqvist, Joakim

AU - Gjertsson, Inger

AU - Glinatsi, Daniel

AU - Kapetanovic, Meliha Crnkic

AU - Aga, Anna-Birgitte

AU - Faustini, Francesca

AU - Parmanne, Pinja

AU - Lorenzen, Tove

AU - Giovanni, Cagnotto

AU - Back, Johan

AU - Hendricks, Oliver

AU - Vedder, Daisy

AU - Rannio, Tuomas

AU - Grenholm, Emma

AU - Ljoså, Maud Kristine

AU - Brodin, Eli

AU - Lindegaard, Hanne

AU - Söderbergh, Annika

AU - Rizk, Milad

AU - Kastbom, Alf

AU - Larsson, Per

AU - Uhrenholt, Line

AU - Just, Søren Andreas

AU - Stevens, David J

AU - Bay Laurbjerg, Trine

AU - Bakland, Gunnstein

AU - Olsen, Inge Christoffer

AU - Haavardsholm, Espen A

AU - Lampa, Jon

AU - NORD-STAR study group

PY - 2023/10

Y1 - 2023/10

N2 - BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025).RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%.CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.TRIAL REGISTRATION NUMBER: NCT01491815.

AB - BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025).RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%.CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.TRIAL REGISTRATION NUMBER: NCT01491815.

KW - Abatacept

KW - Biological Therapy

KW - Certolizumab pegol

KW - Methotrexate

KW - Rheumatoid Arthritis

KW - Abatacept/therapeutic use

KW - Humans

KW - Treatment Outcome

KW - Certolizumab Pegol/therapeutic use

KW - Antirheumatic Agents/adverse effects

KW - Arthritis, Rheumatoid/diagnostic imaging

KW - Drug Therapy, Combination

KW - Methotrexate/therapeutic use

UR - http://www.scopus.com/inward/record.url?scp=85165210988&partnerID=8YFLogxK

U2 - 10.1136/ard-2023-224116

DO - 10.1136/ard-2023-224116

M3 - Journal article

C2 - 37423647

SN - 0003-4967

VL - 82

SP - 1286

EP - 1295

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 10

ER -

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial

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