Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials

Yasuo Nagafuchi; Tjardo D Maarseveen; Kristina Lend; Anna Rudin; Bjorn Gudbjornsson; Dan Nordström; Espen A Haavardsholm; Gerdur Gröndal; Jon Lampa; Kim Hørslev Petersen; Marte Schrumpf Heiberg; Merete Hetland; Mike Nurmohamed; Mikkel Østergaard; Ronald van Vollenhoven; Till Uhlig; Tuulikki Sokka-Isler; Erik B van den Akker; Tom W J Huizinga; Sytske Anne Bergstra; Rachel Knevel

doi:10.1016/j.ard.2026.02.005

Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials

Yasuo Nagafuchi^*, Tjardo D Maarseveen, Kristina Lend, Anna Rudin, Bjorn Gudbjornsson, Dan Nordström, Espen A Haavardsholm, Gerdur Gröndal, Jon Lampa, Kim Hørslev Petersen, Marte Schrumpf Heiberg, Merete Hetland, Mike Nurmohamed, Mikkel Østergaard, Ronald van Vollenhoven, Till Uhlig, Tuulikki Sokka-Isler, Erik B van den Akker, Tom W J Huizinga, Sytske Anne BergstraRachel Knevel

^*Corresponding author af dette arbejde

Afdeling for Rygkirurgi, Led- og Bindevævssygdomme HOC

Abstract

OBJECTIVES: To investigate the association between joint involvement pattern (JIP) subgroups and treatment responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs), and to compare the impact of JIP subgroups with other clinical parameters in treatment-naïve patients with early rheumatoid arthritis (RA).

METHODS: An individual patient data meta-analysis was conducted using 2 randomised controlled trials, NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) and Behandel-Strategieën (BeSt), including 1250 treatment-naïve patients with early RA. JIP subgroup assignment was based on 4 previously identified subgroups defined by baseline clinical characteristics, primarily joint involvement in the 66/68 joint scheme. Treatment outcomes were measured using the longitudinal Clinical Disease Activity Index (CDAI) and other disease activity indices through week 48. Associations of the JIP subgroups and other clinical predictors were evaluated using a mixed-model analysis.

RESULTS: Patients with a hand-dominant JIP (JIP-Hand) showed significantly better CDAI scores after treatment (Beta for CDAI = -1.4 [95% CI, -2.3 to -0.55]; p = .0016), whereas those with a polyarthritis pattern (JIP-Poly) exhibited worse outcomes (Beta = 0.95 [95% CI, 0.064-1.8]; p = .035). Female sex was also associated with worse CDAI scores (Beta = 1.2 [95% CI, 0.40-2.0]; p = .0031), whereas anticitrullinated protein antibodies did not show a significant association (Beta = 0.19 [95% CI, -0.69 to 1.1]; p = .67). When compared across groups, csDMARDs and combined bDMARDs were similarly effective in the respective JIP subgroups (interaction p > .10).

CONCLUSIONS: In early RA, csDMARD and bDMARD treatments resulted in the greatest improvement in disease activity in JIP-Hand and the least improvement in JIP-Poly.

Originalsprog	Engelsk
Tidsskrift	Annals of the Rheumatic Diseases
ISSN	0003-4967
DOI	https://doi.org/10.1016/j.ard.2026.02.005
Status	E-pub ahead of print - 7 mar. 2026

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10.1016/j.ard.2026.02.005Licens: CC BY

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Citationsformater

Nagafuchi, Y., Maarseveen, T. D., Lend, K., Rudin, A., Gudbjornsson, B., Nordström, D., Haavardsholm, E. A., Gröndal, G., Lampa, J., Petersen, K. H., Heiberg, M. S., Hetland, M., Nurmohamed, M., Østergaard, M., van Vollenhoven, R., Uhlig, T., Sokka-Isler, T., van den Akker, E. B., Huizinga, T. W. J., ... Knevel, R. (2026). Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials. Annals of the Rheumatic Diseases. Advance online publication. https://doi.org/10.1016/j.ard.2026.02.005

Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials. / Nagafuchi, Yasuo; Maarseveen, Tjardo D; Lend, Kristina et al.
I: Annals of the Rheumatic Diseases, 07.03.2026.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Nagafuchi, Y, Maarseveen, TD, Lend, K, Rudin, A, Gudbjornsson, B, Nordström, D, Haavardsholm, EA, Gröndal, G, Lampa, J, Petersen, KH, Heiberg, MS, Hetland, M, Nurmohamed, M, Østergaard, M, van Vollenhoven, R, Uhlig, T, Sokka-Isler, T, van den Akker, EB, Huizinga, TWJ, Bergstra, SA & Knevel, R 2026, 'Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials', Annals of the Rheumatic Diseases. https://doi.org/10.1016/j.ard.2026.02.005

Nagafuchi Y, Maarseveen TD, Lend K, Rudin A, Gudbjornsson B, Nordström D et al. Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials. Annals of the Rheumatic Diseases. 2026 mar. 7. Epub 2026 mar. 7. doi: 10.1016/j.ard.2026.02.005

@article{7b9415fbb7da4a7ca867de52f15c1147,

title = "Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials",

abstract = "OBJECTIVES: To investigate the association between joint involvement pattern (JIP) subgroups and treatment responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs), and to compare the impact of JIP subgroups with other clinical parameters in treatment-na{\"i}ve patients with early rheumatoid arthritis (RA).METHODS: An individual patient data meta-analysis was conducted using 2 randomised controlled trials, NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) and Behandel-Strategie{\"e}n (BeSt), including 1250 treatment-na{\"i}ve patients with early RA. JIP subgroup assignment was based on 4 previously identified subgroups defined by baseline clinical characteristics, primarily joint involvement in the 66/68 joint scheme. Treatment outcomes were measured using the longitudinal Clinical Disease Activity Index (CDAI) and other disease activity indices through week 48. Associations of the JIP subgroups and other clinical predictors were evaluated using a mixed-model analysis.RESULTS: Patients with a hand-dominant JIP (JIP-Hand) showed significantly better CDAI scores after treatment (Beta for CDAI = -1.4 [95\% CI, -2.3 to -0.55]; p = .0016), whereas those with a polyarthritis pattern (JIP-Poly) exhibited worse outcomes (Beta = 0.95 [95\% CI, 0.064-1.8]; p = .035). Female sex was also associated with worse CDAI scores (Beta = 1.2 [95\% CI, 0.40-2.0]; p = .0031), whereas anticitrullinated protein antibodies did not show a significant association (Beta = 0.19 [95\% CI, -0.69 to 1.1]; p = .67). When compared across groups, csDMARDs and combined bDMARDs were similarly effective in the respective JIP subgroups (interaction p > .10).CONCLUSIONS: In early RA, csDMARD and bDMARD treatments resulted in the greatest improvement in disease activity in JIP-Hand and the least improvement in JIP-Poly.",

author = "Yasuo Nagafuchi and Maarseveen, \{Tjardo D\} and Kristina Lend and Anna Rudin and Bjorn Gudbjornsson and Dan Nordstr{\"o}m and Haavardsholm, \{Espen A\} and Gerdur Gr{\"o}ndal and Jon Lampa and Petersen, \{Kim H{\o}rslev\} and Heiberg, \{Marte Schrumpf\} and Merete Hetland and Mike Nurmohamed and Mikkel {\O}stergaard and \{van Vollenhoven\}, Ronald and Till Uhlig and Tuulikki Sokka-Isler and \{van den Akker\}, \{Erik B\} and Huizinga, \{Tom W J\} and Bergstra, \{Sytske Anne\} and Rachel Knevel",

year = "2026",

month = mar,

day = "7",

doi = "10.1016/j.ard.2026.02.005",

language = "English",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis

T2 - a combined analysis of NORD-STAR and BeSt trials

AU - Nagafuchi, Yasuo

AU - Maarseveen, Tjardo D

AU - Lend, Kristina

AU - Rudin, Anna

AU - Gudbjornsson, Bjorn

AU - Nordström, Dan

AU - Haavardsholm, Espen A

AU - Gröndal, Gerdur

AU - Lampa, Jon

AU - Petersen, Kim Hørslev

AU - Heiberg, Marte Schrumpf

AU - Hetland, Merete

AU - Nurmohamed, Mike

AU - Østergaard, Mikkel

AU - van Vollenhoven, Ronald

AU - Uhlig, Till

AU - Sokka-Isler, Tuulikki

AU - van den Akker, Erik B

AU - Huizinga, Tom W J

AU - Bergstra, Sytske Anne

AU - Knevel, Rachel

PY - 2026/3/7

Y1 - 2026/3/7

N2 - OBJECTIVES: To investigate the association between joint involvement pattern (JIP) subgroups and treatment responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs), and to compare the impact of JIP subgroups with other clinical parameters in treatment-naïve patients with early rheumatoid arthritis (RA).METHODS: An individual patient data meta-analysis was conducted using 2 randomised controlled trials, NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) and Behandel-Strategieën (BeSt), including 1250 treatment-naïve patients with early RA. JIP subgroup assignment was based on 4 previously identified subgroups defined by baseline clinical characteristics, primarily joint involvement in the 66/68 joint scheme. Treatment outcomes were measured using the longitudinal Clinical Disease Activity Index (CDAI) and other disease activity indices through week 48. Associations of the JIP subgroups and other clinical predictors were evaluated using a mixed-model analysis.RESULTS: Patients with a hand-dominant JIP (JIP-Hand) showed significantly better CDAI scores after treatment (Beta for CDAI = -1.4 [95% CI, -2.3 to -0.55]; p = .0016), whereas those with a polyarthritis pattern (JIP-Poly) exhibited worse outcomes (Beta = 0.95 [95% CI, 0.064-1.8]; p = .035). Female sex was also associated with worse CDAI scores (Beta = 1.2 [95% CI, 0.40-2.0]; p = .0031), whereas anticitrullinated protein antibodies did not show a significant association (Beta = 0.19 [95% CI, -0.69 to 1.1]; p = .67). When compared across groups, csDMARDs and combined bDMARDs were similarly effective in the respective JIP subgroups (interaction p > .10).CONCLUSIONS: In early RA, csDMARD and bDMARD treatments resulted in the greatest improvement in disease activity in JIP-Hand and the least improvement in JIP-Poly.

AB - OBJECTIVES: To investigate the association between joint involvement pattern (JIP) subgroups and treatment responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs), and to compare the impact of JIP subgroups with other clinical parameters in treatment-naïve patients with early rheumatoid arthritis (RA).METHODS: An individual patient data meta-analysis was conducted using 2 randomised controlled trials, NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) and Behandel-Strategieën (BeSt), including 1250 treatment-naïve patients with early RA. JIP subgroup assignment was based on 4 previously identified subgroups defined by baseline clinical characteristics, primarily joint involvement in the 66/68 joint scheme. Treatment outcomes were measured using the longitudinal Clinical Disease Activity Index (CDAI) and other disease activity indices through week 48. Associations of the JIP subgroups and other clinical predictors were evaluated using a mixed-model analysis.RESULTS: Patients with a hand-dominant JIP (JIP-Hand) showed significantly better CDAI scores after treatment (Beta for CDAI = -1.4 [95% CI, -2.3 to -0.55]; p = .0016), whereas those with a polyarthritis pattern (JIP-Poly) exhibited worse outcomes (Beta = 0.95 [95% CI, 0.064-1.8]; p = .035). Female sex was also associated with worse CDAI scores (Beta = 1.2 [95% CI, 0.40-2.0]; p = .0031), whereas anticitrullinated protein antibodies did not show a significant association (Beta = 0.19 [95% CI, -0.69 to 1.1]; p = .67). When compared across groups, csDMARDs and combined bDMARDs were similarly effective in the respective JIP subgroups (interaction p > .10).CONCLUSIONS: In early RA, csDMARD and bDMARD treatments resulted in the greatest improvement in disease activity in JIP-Hand and the least improvement in JIP-Poly.

U2 - 10.1016/j.ard.2026.02.005

DO - 10.1016/j.ard.2026.02.005

M3 - Journal article

C2 - 41796486

SN - 0003-4967

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

ER -