Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe.

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations.

Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study.

OBJECTIVES: To identify a therapeutic target interval for certolizumab pegol drug levels and examine the influence of anti-drug antibodies in patients with inflammatory joint diseases. METHODS: Certolizumab pegol and anti-drug antibody levels were measured in serum samples collected after 3 months of certolizumab pegol treatment in 268 patients with inflammatory joint diseases (116 axial spondyloarthritis, 91 rheumatoid arthritis and 61 psoriatic arthritis) in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score Clinically important improvement in axial spondyloarthritis, European League Against Rheumatism good/moderate response in rheumatoid arthritis, and improvement in 28-joint Disease Activity Score of ≥ 0.6 in PsA. Serum drug levels and anti-drug antibodies were analysed using automated in-house assays. RESULTS: Certolizumab pegol serum levels varied considerably between individuals (median (IQR) 32.9 (17.3-43.9) mg/L). Certolizumab pegol level ≥ 20 mg/L was associated with treatment response for the total inflammatory joint disease population, with odds ratio (OR) 2.3 (95% CI 1.2-4.5, P = 0.01) and OR 1.9 (95% CI 1.0-3.5, P = 0.05) after 3 and 6 months of treatment, respectively. For individual diagnoses, this association was most consistent for axial spondyloarthritis, with OR 3.4 (95% CI 1.0-11.1, P < 0.05) and OR 3.3 (95% CI 1.0-10.8, P < 0.05), respectively. Certolizumab pegol level > 40 mg/L was not associated with any additional benefit for any of the diagnoses. Anti-drug antibodies were detected in 6.1% (19/310) of samples and were associated with low certolizumab pegol levels (P < 0.01). CONCLUSIONS: Serum certolizumab pegol levels 20-40 mg/L were associated with treatment response in inflammatory joint diseases. Our study is the first to show this association in axial spondyloarthritis and psoriatic arthritis patients. The results suggest a possible benefit of therapeutic drug monitoring in patients with inflammatory joint disease on certolizumab pegol treatment. TRIAL REGISTRATION: NCT01581294, April 2012.

Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register.

OBJECTIVES: To examine cross-sectional and longitudinal relationships between fibromyalgia (FM) and rheumatoid arthritis (RA) disease activity. METHODS: 636 patients in the observational Oslo RA register (ORAR) were invited to a clinical examination in 1999. 28-tender and swollen joint counts (TJC, SJC) and 18-tender points were assessed, the RA disease activity score (DAS-28) calculated. Fibromyalgia (FM) was diagnosed according to 1990 (FM-1990) and modified 2011 (mFM-2011) ACR criteria. At the 10-year follow-up patients completed the RA Disease Activity Index (RADAI) and Routine Assessment of Patient Index Data 3 (RAPID-3). Baseline and 10-year RA disease activity were compared across presence/absence of FM. Linear regression models were constructed with 10-year RADAI and RAPID-3 as outcome. RESULTS: 502 patients participated at baseline data-collection and 10-year data was available in 236. At baseline, mean (SD) age was 59.5 (12.5) years and 87% were female. 9% and 30% had FM-1990 and mFM-2011 respectively. RA-FM patients were predominantly female with higher SJC, TJC, and DAS-28 at baseline. Baseline RA-FM predicted higher levels of RADAI and RAPID-3 at the 10-year follow-up. CONCLUSIONS: RA-FM was associated with significantly higher levels of cross-sectional and longitudinal RA disease activity. FM should be considered in patients with RA not reaching remission.

Mapping the Effect of Psoriatic Arthritis Using the International Classification of Functioning, Disability and Health.

OBJECTIVE: The effect of a disease can be categorized by a standardized reference system: the International Classification of Functioning, Disability and Health (ICF). The objective was to map the effect of psoriatic arthritis (PsA) from the patient's perspective to the ICF. METHODS: A systematic literature review was performed. Qualitative publications reporting domains of impact important for patients with PsA were identified using the following terms: ("psoriatic arthritis") AND ("quality of life" OR "impact"). Meaningful concepts were extracted from the publications, grouped into domains and linked to the ICF categories. The number of concepts linked to each ICF category and to each ICF level was calculated. The number of concepts not linkable was also calculated. RESULTS: Eleven studies (13 articles) were included in the analysis. Twenty-five domains of impact were cited, of which the ability to work/volunteer and social participation were the most cited (both by 10 studies). In total, 258 concepts were identified, of which 217 could be linked to 136 different ICF categories; 41 concepts, mostly personal factors, could not be precisely linked. The most represented ICF component was activities and participation (42.6%) rather than body structures (10.3%) or body functions (29.4%). Ten studies (90.9%) reported impairments in the ability to work/volunteer and social participation, and 7 (63.6%) reported leisure activities, family and intimacy, pain, skin problems, and body image. CONCLUSION: PsA widely affects all aspects of patients' lives, in particular aspects related to activities and participation. The ICF is a useful approach for the classification of disease effect.

The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

BACKGROUND: Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. METHODS: Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. RESULTS: Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] µmol/L vs. 0.02 [0.07] µmol/L, P = 0.42, 12 months: 0.01 [0.08] µmol/L vs. 0.01 [0.09] µmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. CONCLUSION: Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients.

Changes in arterial stiffness during continued infliximab treatment in patients with inflammatory arthropathies.

Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased risk of cardiovascular disease. TNF-α antagonists may improve vascular function in these patients and thus be beneficial with regard to cardiovascular disease. This study evaluated arterial stiffness and disease activity between two infusions with a TNF-α antagonist (infliximab) in patients with inflammatory arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic pulse wave velocity (aPWV), and disease activity were measured in 17 patients with RA, AS, or PsA who had been treated with infliximab for at least 12 months. The patients were examined immediately before their infliximab infusion and thereafter every 10th day until their next infusion scheduled at week 4-8. AIx and aPWV did not change during the period between two infliximab infusions. The patients had a temporary improvement in the general disease activity assessed on visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02) after the infusion. In the group of patients with RA, the Disease Activity Score (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did not alter aortic pulse wave velocity or augmentation index in patients with inflammatory arthropathies who were on long-term infliximab therapy. Reductions in the general disease activity and DAS28 were not reflected in alterations of aortic stiffness or augmentation index.

Identification of cutpoints for acceptable health status and important improvement in patient-reported outcomes, in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

OBJECTIVE: To identify cutpoints reflecting Patient Acceptable Symptom State (PASS) and Minimal Clinically Important Improvement (MCII) in patient-reported multi-attribute health status classification systems and health status measurements among patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). METHODS: We identified patients with RA, AS, and PsA from the Norwegian disease-modifying antirheumatic drug (DMARD) register (NOR-DMARD). The patients (n = 4225) had started with DMARD and responded to the PASS and MCII anchoring questions at the 3-month followup examination. Receiver operating characteristics (ROC) curves with 80% specificity and the 75th percentile approach were used to identify PASS and MCII cutpoints in the EuroQol-5 Dimensions (EQ-5D) and the Short-Form-6 Dimensions (SF-6D) indexes, but also in other patient-reported outcomes (joint pain and patient global visual analog scale and Modified Health Assessment Questionnaire). RESULTS: The PASS cutpoints estimated with 80% specificity were around 0.70 in EQ-5D in all diseases and around 0.65 in SF-6D. The cutpoints were around 0.65 and 0.60, respectively, when the 75th percentile approach was used. The MCII cutpoints assessed by 80% specificity varied from 0.10 to 0.19 in EQ-5D and from 0.07 to 0.10 in SF-6D. CONCLUSION: The cutpoints for PASS in EQ-5D and SF-6D indicate that PASS corresponds to a health-related quality of life that is far from perfect health. Somewhat different cutpoints were identified for both PASS and MCII with 80% specificity versus the 75th percentile method.

Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study.

The chronic inflammatory state of rheumatoid arthritis and other inflammatory arthropathies, such as ankylosing spondylitis and psoriatic arthritis, contributes to the accelerated atherosclerosis associated with these conditions. This study evaluates the effect of treatment with tumor necrosis factor (TNF)-alpha antagonists on arterial stiffness in patients with inflammatory arthropathies. A total of 60 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and clinical indication for anti-TNF-alpha therapy were included. Thirty-five patients started with anti-TNF-alpha therapy and were compared with a nontreatment group of 25 patients. Aortic stiffness (aortic pulse wave velocity), augmentation index, and disease activity were assessed at baseline and after 3 months. Aortic pulse wave velocity (mean+/-SD) was reduced in the treatment group but not in the control group (-0.50+/-0.78 m/s versus 0.05+/-0.54 m/s, respectively; P=0.002). Concomitantly, C-reactive protein and the disease activity score were reduced in the treatment group (-9.3+/-20.2 mg/L [P<0.001] and -0.74+/-0.91 [P=0.004]). Augmentation index remained unchanged in both groups (0.1+/-7.1% versus -1.0+/-5.8%, respectively; P=0.53). In a multivariate linear regression model, only treatment with TNF-alpha antagonist and change in mean arterial pressure predicted alterations in aortic pulse wave velocity. In summary, anti-TNF-alpha therapy improved aortic stiffness in patients with inflammatory arthropathies. These findings support the idea that anti-inflammatory treatment has a favorable effect on cardiovascular risk in patients with inflammatory arthropathies.