Annals of the rheumatic diseases · 2026
Difficult-to-manage and treatment-refractory psoriatic arthritis in patients treated with biological and targeted synthetic DMARDs: prevalence and characteristics in 5 Nordic registries.
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Nielung Louise Majormoen, Giuseppe Daniela Di, Hetland Merete Lund, Askling Johan, Nordström Dan C, Provan Sella Aarrestad, Gudbjornsson Bjorn, Palsson Olafur, Delcoigne Bénédicte, Dreyer Lene Wohlfahrt, Michelsen Brigitte, Wallman Johan Karlsson, Glintborg Bente
Аннотация
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.
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.