Background/Purpose: Undifferentiated arthritis (UA) is considered to be heterogenous and consists of subgroups, this notion is affirmed by differences in disease course, varying from spontaneous resolution of arthritis to RA-development. We aimed to identify homogeneous subgroups within UA based on a combination of clinical features and thereafter to relate these to the outcomes spontaneous resolution and RA-development.

Methods: We studied patients with UA, defined as not-fulfilling 1987-/2010-RA-criteria nor having an alternate diagnosis, consecutively included in the Leiden Early Arthritis Clinic between 1993-2006 and who were autoantibody-negative. Before 2006 DMARD-treatment of UA was infrequent, hence limiting possible influence of DMARD-treatment on outcomes. Latent Class Analysis was used to identify subgroups based on a combination of clinical features (e.g. symptom characteristics, physical examination, laboratory tests). Test-characteristics were used to assess the relation of the subgroups with two long-term outcomes: achieving spontaneous-resolution (defined as spontaneous resolution of arthritis without DMARD-treatment) and RA-development.

Results: 310 consecutive UA-patients were studied. Five classes were identified, location and number of swollen joints were most distinguishing. Classes were characterized by: 1) polyarthritis, often symmetric 2) oligoarthritis, frequently with (sub)acute onset, 3) wrist-monoarthritis, often with (sub)acute onset, increased BMI and without morning stiffness, 4) small-joint monoarthritis, often without increased acute phase reactants, and 5) large-joint monoarthritis, often with (sub)acute onset. Studying the classes in relation to the outcomes revealed that the majority of patients with absence of spontaneous resolution were not included in the classes characterized by monoarthritis (specificity >90%). In addition, patients who developed RA were mainly not in the monoarthritis classes (sensitivity < 7%).

Conclusion: Using a data-driven unsupervised approach, five subgroups within contemporary UA were identified in this unique historical cohort of contemporary UA-patients. These subgroups have differences in clinical outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/detangling-heterogeneity-in-contemporary-undifferentiated-arthritis-a-large-cohort-study-using-latent-class-analysis/