Reappraisal of the diagnostic and prognostic value of morning stiffness in arthralgia and early arthritis: results from the Groningen EARC, Leiden EARC, ESPOIR, Leiden EAC and REACH

Abstract

Introduction: Morning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).

Methods: In arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.

Results: In arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.

Conclusions: Morning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.

Figure 1

Outline of study questions. Of the 2010-RA patients in the EAC, radiographs were scored for the patients included between 1993 and 2006 (n = 636). Baseline characteristics of RA patients included before or after 2006 were not different. In ESPOIR, radiographic data was available for 659 of 677 RA patients. Here also, baseline characteristics of patients with and without radiographs were not different. EAC, Early Arthritis Clinic; ESPOIR, Evaluation et Suivi de POlyarthrites Indifférenciées Récentes; RA, rheumatoid arthritis.

Figure 2

The duration of morning stiffness per diagnosis in the Leiden EAC. The black horizontal line indicates the median duration. Number of patients per diagnosis after one year of follow-up: 2010-RA n = 1,140, SLE with peripheral arthritis n = 21, sarcoidosis n = 78, RS3PE n = 60, inflammatory arthritis n = 133, reactive arthritis n = 108, SpA/PsA with peripheral arthritis n = 287, crystal arthritis n = 119. Two data points (2010-RA n = 1 and SpA/PsA with peripheral arthritis n = 1) are outside the axis limits. EAC, Early Arthritis Clinic; PsA, psoriatic arthritis; RA, rheumatoid arthritis; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; SLE, systemic lupus erythematosus; SpA, spondyloarthritis.

Figure 3

ROC curves on morning stiffness in early arthritis patients of the EAC (A) and ESPOIR (B). The AUCs were 0.68 in the EAC and 0.64 in ESPOIR. In the EAC, the optimal cutoff point (crossing of dashed lines) reflected a sensitivity of 77% and a specificity of 52%; morning stiffness duration at this point was 27.5 minutes. When selecting the point with 80% specificity, the sensitivity was 40% and the morning stiffness duration 67.5 minutes (EAC) and a sensitivity of 33% and a morning stiffness duration 62.5 minutes (ESPOIR). AUC, area under the receiver operating characteristic curve; EAC, Early Arthritis Clinic; ESPOIR, Evaluation et Suivi de POlyarthrites Indifférenciées Récentes.