title: 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: BACKGROUND
  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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZC, Leiden, the Netherlands. j.a.b.van_nies@lumc.nl.
authors.forename: Jessica A B
authors.initials: JA
authors.lastname: van Nies
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands. c.alves@eramusmc.nl.
authors.forename: Celina
authors.initials: C
authors.lastname: Alves
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands. a.l.s.radix-bloemen@umcg.nl.
authors.forename: Audrey L S
authors.initials: AL
authors.lastname: Radix-Bloemen
authors.affiliation: Department of Rheumatology, Nîmes University Hospital; EA 2415, Montpellier I University, 4 Rue du Professeur Robert Debré, 30029, Nîmes, France. cecilegaujouxviala@yahoo.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Gaujoux-Viala
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZC, Leiden, the Netherlands. t.w.j.huizinga@lumc.nl.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands. j.hazes@erasmusmc.nl.
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center, Antonius Deusinglaan 1, 9713 AV, Groningen, the Netherlands. e.brouwer@umcg.nl.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Department of Rheumatology, Université Pierre et Marie Curie Curie - Paris 6, GRC08, Institut Pierre Louis de d'Epidémiologie et Santé Publique, Pitie-Salpetriere Hospital, 47-83 Boulevard de l'Hôpital, 75013, Paris, France. bruno.fautrel@psl.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fautrel
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZC, Leiden, the Netherlands. a.h.m.van_der_helm@lumc.nl.
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D019540:Area Under Curve; D018771:Arthralgia / Q000175:diagnosis*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires