Patients improve, patterns persist: longitudinal stability of RA joint involvement patterns

OBJECTIVE: Rheumatoid arthritis is a heterogeneous disease. Data-driven approaches, from synovial histology to joint involvement patterns (JIPs), have sought to define clinically meaningful subgroups. Whether these subgroups represent stable phenotypes or transient disease states remains unclear. We aimed to develop a novel analytical method to measure longitudinal stability of these subsets. METHODS: We analyzed two randomized controlled trials, NORD-STAR (NOrdic Rheumatic Diseases Strategy Trials And Registries; n=630), BeSt (Behandel-Strategieën, n=445) and one real-world cohort (Reumazorg Zuidwest Nederland (RZWN), n=252), all treated with DMARDs under a treat-to-target strategy. Patients were assigned to previously defined JIP-subgroups based on shared clinical features. Disease progression was then tracked over one year along the two principal axes of JIP variation: overall severity (oligoarticular vs. polyarticular) and anatomical distribution (hand vs. foot). Longitudinal stability was assessed by measuring how phenotypically similar each patient remained to others sharing their initial joint pattern, quanitified using silhouette-like scores. RESULTS: Effective treatment led to convergence toward mild disease. Nevertheless, patients sharing similar baseline JIPs maintained clustering together over time significantly more than expected by chance in BeSt (P=0.018-0.038), NORD-STAR (P=0.004-0.017), and RZWN (P<0.001), except for JIP-poly in BeSt and JIP-oligo in NORD-STAR. When stratifying by anatomical region, we found that improvement in foot involvement lagged behind hand involvement across trials. CONCLUSION: Patients with similar baseline joint involvement patterns maintain phenotypic similarity over time, suggesting JIP subgroups reflect distinct, stable phenotypes rather than transient disease states. Our tool is available to study the longitudinal stability of any subset.

Authors

Institutions

Publication Details

Journal
Arthritis Care & Research
Published
2026-10-05
DOI
https://doi.org/10.1002/acr.80174
Primary Topic
Rheumatoid Arthritis Research and Therapies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Patients improve, patterns persist: longitudinal stability of RA joint involvement patterns

Espen Andre Haavardsholm, Marcel J. T. Reinders, Ronald van Vollenhoven, Gerður Gröndal et al.
Arthritis Care & Research
Rheumatoid Arthritis Research and Therapies
article

Patients improve, patterns persist: longitudinal stability of RA joint involvement patterns

Espen Andre Haavardsholm, Marcel J. T. Reinders, Ronald van Vollenhoven, Gerður Gröndal, Rachel Knevel, Kim Hørslev Petersen, Erik B. van den Akker, Yasuo Nagafuchi, Kristina Lend, Till Uhlig, Dan Nordström, Björn Guðbjörnsson, Herman Kasper Glas, Merete Lund Hetland, Michael Twahier Nurmohamed, Tjardo Daniël Maarseveen, Mikkel Østergaard, Jon Lampa, Anna Rudin, Sytske Anne Bergstra, Marte Schrumpf Heiberg, Josien Veris-van Dieren, Tuulikki Sokka‐Isler, Tom Huizinga, Seyam Alemyar
article en

Abstract

OBJECTIVE: Rheumatoid arthritis is a heterogeneous disease. Data-driven approaches, from synovial histology to joint involvement patterns (JIPs), have sought to define clinically meaningful subgroups. Whether these subgroups represent stable phenotypes or transient disease states remains unclear. We aimed to develop a novel analytical method to measure longitudinal stability of these subsets. METHODS: We analyzed two randomized controlled trials, NORD-STAR (NOrdic Rheumatic Diseases Strategy Trials And Registries; n=630), BeSt (Behandel-Strategieën, n=445) and one real-world cohort (Reumazorg Zuidwest Nederland (RZWN), n=252), all treated with DMARDs under a treat-to-target strategy. Patients were assigned to previously defined JIP-subgroups based on shared clinical features. Disease progression was then tracked over one year along the two principal axes of JIP variation: overall severity (oligoarticular vs. polyarticular) and anatomical distribution (hand vs. foot). Longitudinal stability was assessed by measuring how phenotypically similar each patient remained to others sharing their initial joint pattern, quanitified using silhouette-like scores. RESULTS: Effective treatment led to convergence toward mild disease. Nevertheless, patients sharing similar baseline JIPs maintained clustering together over time significantly more than expected by chance in BeSt (P=0.018-0.038), NORD-STAR (P=0.004-0.017), and RZWN (P<0.001), except for JIP-poly in BeSt and JIP-oligo in NORD-STAR. When stratifying by anatomical region, we found that improvement in foot involvement lagged behind hand involvement across trials. CONCLUSION: Patients with similar baseline joint involvement patterns maintain phenotypic similarity over time, suggesting JIP subgroups reflect distinct, stable phenotypes rather than transient disease states. Our tool is available to study the longitudinal stability of any subset.

Arthritis Care & Research
University of Copenhagen (DK), Karolinska University Hospital (SE), University of Helsinki (FI), Jichi Medical University (JP), University of Iceland (IS), University of Eastern Finland (FI), University of Southern Denmark (DK), University of Oslo (NO), Leiden University Medical Center (NL), Helsinki University Hospital (FI), Sahlgrenska University Hospital (SE), Glostrup Hospital (DK), Karolinska Institutet (SE), Reade (NL), Amphia Ziekenhuis (NL), National University Hospital of Iceland (IS), Region of Southern Denmark (DK), Diakonhjemmet Hospital (NO), Central Finland Health Care District (FI), Sygehus Sønderjylland (DK), Amsterdam University Medical Centers (NL), Newcastle University (GB), University of Gothenburg (SE), University of Amsterdam (NL), Delft University of Technology (NL)
Openalex Percentile: Top 11%
Rheumatoid Arthritis Research and Therapies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.