Background/Purpose: Rheumatoid arthritis (RA) is characterised by the presence of a progressively destructive joint inflammation. Even in times of modern therapeutics, a subgroup of patients continues to be refractory to numerous consecutive therapeutic interventions with regards to control of inflammation and joint damage.   Objective: To explore the characteristics and causes of refractory RA in 2016.  

Methods: We defined refractory RA as patients who had experienced ³3 treatment courses (with at least one biological) over a minimum of 18 months since diagnosis without reaching the treatment goal of low disease activity or remission (defined by a Simplified Disease Activity Index, SDAI, ³11). From our clinicÕs ongoing longitudinal data set we identified 64 refractory patients out of 737 RA outpatients. This is an interim report of the first 30 of these patients, who were prospectively included in our study (figure 1). Radiographic images were obtained prospectively, and were retrospectively scored by an experienced reader using the modified Sharp/van der Heijde (SvH) method. Average changes in SvH scores of ³3 per year were considered as progressive. After enrolment, we performed ultrasound examination of the hands among these refractory patients and semi-quantitatively scored them for signs of Greyscale and Power Doppler.  

Results: 15 out of 30 (50.0%) patients showed radiographic progression (figure). In this group, almost every patient (86.7%) also showed signs of ultrasound activity (Power Doppler signs grade 2 or 3). Radiographic progressive patients showed significantly fewer tender joints than patients being non-progressive (p=0.032) (table).  Of the 15 non-progressive refractory patients, 8 were diagnosed with fibromyalgia by the ACR 2010 fibromyalgia diagnostic criteria, and accordingly had failed their treatment target due to high patient global scores and tender joint counts. The remaining seven had active synovitis, which was confirmed in five patients by ultrasound. Regardless of radiographic or sonographic state, patients evaluate their state of disease activity the same (Patient Global Assessment, PGA: 57.3 vs 62.2, p=0.502; or 59.9 vs 59.1, p=0.925; respectively).

Conclusion: There a several different types of patients being referred as ÒrefractoryÓ. Whereas almost all radiographic progressing patients also show signs of active synovitis by ultrasound, most non-progressing patients do not and are mainly classified as refractory due to pain components. Here, our clinical composite indices fail.