Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

OBJECTIVES: To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. METHODS: Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. RESULTS: We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. CONCLUSION: In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.

Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study.

OBJECTIVES: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe. METHODS: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders). RESULTS: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates. CONCLUSION: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.

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.

Area of Residence and Socioeconomic Factors Reduce Access to Biologics for Rheumatoid Arthritis Patients in Romania.

INTRODUCTION: The study aimed to evaluate the influence of socioeconomic factors on rheumatoid arthritis (RA) patients' access to biologics in Romania. METHOD: Cross-sectional data were collected in January 2014 from the Romanian Registry of Rheumatic Diseases (RRRD) comprising all RA patients on biologics from 42 Romanian counties. "Territorial" access to biologics was defined by patients receiving biologics in their home county. A county was "equitable" if <25% of RA patients received biologics outside it. RESULTS: The RRRD included 4507 RA patients aged 56.7 ± 12.1 years, with a disease duration of 12.1 ± 8.3 years. Urban dwellers (67.8%) had a significantly higher prevalence of territorial biologic access than rural dwellers (83.1% compared to 74.1%; p < 0.001). Gross domestic product (GDP) in 1000 €/capita/county (odds ratio (OR) = 1.224) and number of physicians/1000 inhabitants/county (OR = 2.198) predict territorial access to biologics and also predict the number of territorially treated RA patients. Inequitable counties exhibited significantly lower socioeconomic indicators than equitable counties. CONCLUSION: In Romania, RA patients' access to biologics varies significantly between counties. Urban dwellers and patients living in counties/regions with high living standards are more likely to receive biologics locally than those living in more deprived areas.

Trends of rheumatoid arthritis monitorization in Romania.

BACKGROUND: rheumatoid arthritis (RA) is associated with the loss of overall functionality, which leads to substantial economic losses. Second line agents used in RA treatment require careful monitorization in terms of efficiency and tolerability. OBJECTIVE: trends, predictive factors and characteristics of clinical, biological and radiological RA monitorization in a cross sectional observational cohort study, conducted on over 206 patients in Romania, with a 12 months follow up (December 2007 - December 2008). METHOD: Cases were recruited from the south-west region of the country, covering a geographical area of 23 counties. Patients were invited to complete three sets of interviews (collected by post) in a consent letter, containing self reported questionnaires, at 6 months intervals: an original questionnaire (which included quantitative self reported of pain, disease activity and fatigue on visual analogue scale-VAS), Health Assessment Questionnaire-HAQ-Disability and Discomfort Scales and EUROQOL EQ-5D, validated in Romanian (obtaining a user agreement by authors of the original version). RESULTS: analysis was carried out in SPSS 10. The cohort enrolled 206 patients, with the average age of 54.90 +/- 12.67 years, 66% urban, 86.4% women, 29.1% professionally active, 48.5% graduates of primary education. The average disease duration after diagnosis of RA was of 9.40 +/- 8.87 years. The duration of the treatment reported at baseline was of 2.70 +/- 2.64 years. Most patients followed a program of monthly monitoring at a general practitioner (GP) (41.7% at baseline and 37.1% to 12 months). Visits to the rheumatologist followed a monthly regimen (32.3% at baseline and 31.7% to 12 months) or a 2 months interval (19.4% at baseline and 29.6% to 12 months, p = 0.000). Biological monitoring was quarterly (39.6% and 53.2% at 12 months; p = 0.000) or at 2 months interval (26.2% at baseline and 16.7% to 12 months, p = 0.000). X-ray monitoring lacked in over half the cases in a year of disease progression (63.3% at 6 months and 62.2% at 12 months), although it sums between 1 and 3 radiographs to one third of the cases (36.8%), CONCLUSION: generally, in our country, there is a lack of aggregation in the dispensarization algorithm of patients with RA; consequently, the decision is awarded to the human factor. Under these circumstances, some patients are over evaluated. Promoting a dispensarization guide for RA patients could induce benefits both clinically and economically. Therefore, we submit a proposal of recommendations as a guideline for clinical, biological and radiological monitoring, according to the phase and stage of RA.

Rheumatoid arthritis: travelling biological era a Romanian X-ray population.

BACKGROUND: Rheumatoid arthritis (RA) is associated with loss of overall functionality of the locomotion system and it is connected with substantial economic losses. OBJECTIVE: To describe the clinical characteristics and healthcare resource utilization characteristics and to analyze the correlations in a cross-sectional sample of 206 patients in Romania. METHOD: RA cases have been enrolled from southern and western part of the country, covering a surface of 23 counties. RESULTS: Particularly in the literature data, Romanian RA patients become work disabled at 5.65 +/- 5.99 years old after the diagnosis. At cohort level, retirement in the first year after RA diagnosis is of 22.9%. From those, 13% were treated with biologic DMARDs; those on non-biologic DMARDs were 28.6%. In oral therapy group the most prescribed drug is lefunomide (61.2%). RA has an important impact on pain, function and utility, influenced by social factors. Patients' follow up is often based on hospitalization. CONCLUSION: Currently, when the clinician may choose for one certain therapy or another, the social influence is still overwhelming at all the evaluation levels in RA patients, as well as at economic impact.