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Poly-Refractory Rheumatoid Arthritis

Feb 08, 2024 5:22 pm

Refractory of difficult to treat (D2T-RA) rheumatoid arthritis (RA) comprises a minority of patients that can be categorized by clinical and imaging parameters to formulate a better therapeutic approach. 

A cross-sectional study of 1,591 RA treated with b/tsDMARDs were categorized as either D2T-RA  (by EULAR criteria) or further subclassified as poly-refractory if they experienced inefficacy/toxicity to at least one drug of all classes.  A subset of these underwent joint evaluation by ultrasound (US) for the presence of synovitis. 

Patients either had persistent inflammatory refractory RA (PIRRA) or noninflammatory refractory RA (NIRRA), based on objective ultrasound (US) synovitis. The purpose of the study was to find distinct clinical phenotypes Correlating with either D2T-RA or poly-refractory RA.

From a total of 1469 RA patients, 247 (16.8%) had D2T-RA; but only 40 (2.7%) had failed all 4 drug classes and were poly-refractory RA.

When compared to D2T-RA, poly-refractory RA patients were more likely to have:

  • Higher DAS28-CRP (5.4 vs 5.02, P < 0.05)
  • Higher CRP levels (13 vs 5 mg/l, P < 0.01)
  • History of smoking (ever) (20% vs 4%, P < 0.01) (OR 5.1; P = 0.002).

Only 107/247 patients with D2T-RA had a US evaluation:

  • 57% were PIRRA
  • 43% were  NIRRA.

NIRRA patients had higher BMI (30 vs 26, P < 0.001), more fibromyalgia (15% vs 3%, P < 0.05), lower swollen joint count (: 2 vs 5, P < 0.001), and lower CRP levels (5 vs 10, P < 0.01).

Poly-refractory RA patients make only 2.7% of all RA patients and were more likely to have been smokers.

Among D2T-RA, 60% may still have inflammatory activity and 40% will be non-inflammatory and less likely to respond to innovative strategies or additional b/tsDMARDs.


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The author has no conflicts of interest to disclose related to this subject