ObjectivesTo compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA−) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time.MethodsAll UA (n = 130), RA− (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO.ResultsRA− patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA− patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA− compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity.ConclusionRA− patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients’ lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity.Trial registrationISRCTN26791028.