Difficult-to-manage and treatment-refractory psoriatic arthritis in patients treated with biological and targeted synthetic DMARDs: prevalence and characteristics in 5 Nordic registries
In brief
About 2% of psoriatic arthritis patients become difficult-to-manage and 1.2% develop treatment-refractory disease despite multiple biologic
In five Nordic registries of 14,362 patients starting a biologic or targeted synthetic DMARD, 36% stopped at least two agents, yet only 2% met all criteria for difficult-to-manage disease and 1.2% were classified as treatment-refractory, with higher rates among women, those with depression, and opioid users. The findings underscore the rarity but complexity of truly refractory PsA and the need for prospective validation of EULAR definitions.
- Journal
- Annals of the rheumatic diseases (Q1)
- Published
- 4 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Louise Majormoen Nielung, Daniela Di Giuseppe, Merete Lund Hetland, Johan Askling, Dan C Nordström, Sella Aarrestad Provan, et al.
- PMID
- 42697827
- DOI
- 10.1016/j.ard.2026.08.002
Why clinicians should know about it
- Picked for Rheumatology (top studies of the week, 6 September 2026): Real‑world prevalence of difficult‑to‑manage PsA on b/tsDMARDs
Abstract
OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) recently proposed a framework for 'difficult-to-manage' (D2M) and 'treatment-refractory' disease in psoriatic arthritis (PsA). We explored real-world prevalence and characteristics of patients fulfilling registry-based components inspired by EULAR's framework among patients with PsA initiating biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD). METHODS: Cohort study from 5 Nordic biologics registries with follow-up of patients initiating first b/tsDMARD 1999 to 2020. First (step 1a), 3 cohorts were defined: discontinuation of ≥2, ≥3, or ≥4 b/tsDMARDs, respectively. Additional components were added sequentially to each cohort: (1b) b/tsDMARD-discontinuation reason (inefficacy/side effects); (1c) discontinuation of ≥2 different mechanisms of action (with 1a+1b+1c providing nuanced understanding of switching patterns); (2) problematic signs/symptoms (patient global score ≥ 30 mm); (3) persistent disease activity (tender/swollen joint count ≥1, C-reactive protein [CRP] > 10 mg/L, or Disease Activity index in PSoriatic Arthritis 28-joint counts >14). Treatment-refractory disease required primary/secondary b/tsDMARD inefficacy (not side-effects/intolerability/contraindications), and objective inflammation (tender/swollen joint count ≥ 1, or CRP > 10 mg/L). RESULTS: Among 14,362 patients, discontinuation of ≥2/≥3/≥4 b/tsDMARDs occurred in 36%/18%/10%, respectively, during a median(IQR) follow-up of 6.3 years (2.4-10.7). Applying all components (1a-3), D2M prevalences were 2%/3%/3%, respectively. Corresponding treatment-refractory prevalences were 1.2%/1.2%/0.8%, respectively. Female sex, depression, and opioid use increased with the number of b/tsDMARD discontinuations. CONCLUSIONS: In routine care, multiple b/tsDMARD discontinuations were common. Two percent were D2M, and 1.2% were treatment-refractory, both characterised by a higher prevalence of women, depression, and opioid use. Although our retrospective design did not allow testing of the EULAR definitions, our findings highlight the complexity of D2M and treatment-refractory PsA and underline the need for prospective studies.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.