OBJECTIVE:Identifying patient characteristics that predict treatment response in psoriatic arthritis (PsA) may help optimize treat-to-target strategies. We aimed to explore overall and sex-specific predictors of secukinumab (SEC) effectiveness in European patients with PsA treated in routine care. METHODS:We analyzed data from 14 registries in the European Spondyloarthritis (EuroSpA) Research Collaboration. Patients aged ≥ 18 years at diagnosis, initiating SEC treatment from January 2015 to January 2021, were included. Multiple imputation was used for missing covariates at treatment start (baseline) and Disease Activity Index for Psoriatic Arthritis based on 28 joints (DAPSA28) at 6 months. Overall and sex-stratified analyses were performed by logistic and Cox regressions to identify baseline predictors of the following treatment outcomes: (1) DAPSA28 low disease activity (LDA; DAPSA28 ≤ 14) at 6 months, (2) DAPSA28 moderate response at 6 months, and (3) SEC discontinuation within 12 months. RESULTS:In total, 2790 patients (43% male) were included. Median age was 43 years (IQR 34-52), and SEC was the first-line biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in 665 patients (24%). Positive predictors for both DAPSA28 LDA and DAPSA28 moderate response were male sex, fewer previous b/tsDMARDs, C-reactive protein (CRP) > 10 mg/L, and lower Health Assessment Questionnaire (HAQ) score. Absence of psoriasis, higher patient fatigue, and tender joint counts predicted SEC discontinuation within 12 months. For some outcomes, sex-specific predictors were fewer previous b/tsDMARDs and CRP > 10 mg/L among male patients and lower patient fatigue score among female patients. CONCLUSION:We identified overall and sex-specific predictors of SEC effectiveness in European patients with PsA. Our findings may support personalized treatment decisions.

Aims:This study aimed to describe the prevalence and characteristics (sources, motivations, perceived health risks, accessibility) of medical use and misuse of addictive prescription drugs (APDs), and the prevalence of poor mental wellbeing and self-harm among adolescents in Estonia. In addition, this study examined associations between APD use status (non-use, medical use, misuse) and mental health indicators (mental wellbeing, self-harm). Methods:Data came from the nationally representative 2024 European School Survey Project on Alcohol and Other Drugs (ESPAD) survey of 15-16-year-olds in Estonia (n = 2,019). Respondents were classified as non-users, medical users, or misusers based on lifetime APD use. Motivations, sources, perceived health risks, accessibility, mental wellbeing, and self-harm were assessed. Multivariable logistic regression examined associations between APD use status and mental health indicators. Results:Overall, 27.8% of adolescents reported APD medical use and 18.3% misuse, with higher prevalence among girls. Sedatives and sleeping pills were the most commonly medically used and misused APDs. Most misused APDs were obtained from home, and self-treatment motives predominated. Poor mental wellbeing (44.4%) and self-harm (17.6%) were most prevalent among misusers. APD misuse (. non-use) was associated with poor mental wellbeing, self-harm and female gender; misuse (vs. medical use) with self-harm; and APD medical use (vs. non-use) with self-harm and female gender. The strongest association was found between APD misuse (vs. non-use) and self-harm (adjusted odds ratio = 2.78). Conclusions:APD medical use and misuse are common among Estonian adolescents. APD misuse co-occurred with poor mental wellbeing and self-harm, highlighting the importance of integrating APD misuse prevention into broader adolescent mental health and substance use strategies.

Objectives To investigate associations between cardiometabolic comorbidities and clinical characteristics, prescription patterns and retention of first biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) in patients with psoriatic arthritis (PsA).Methods Patients with PsA initiating a first b/tsDMARD treatment in 2015 or later were identified in eight European rheumatology registries. Patients with information on five cardiometabolic comorbidities (obesity, dyslipidaemia, diabetes, hypertension, ischaemic heart disease) at treatment start (baseline) were included. All analyses were conducted according to patients’ comorbidity burden (count: 0/1/≥2) and status (presence/absence of each comorbidity). Patient characteristics and prescription patterns were described. Twelve-month treatment retention rates were estimated and compared using Kaplan-Meier plots, log-rank tests and multivariable Cox regression analyses.Results Among 5299 patients, 36% had at least one cardiometabolic comorbidity. Patients with comorbidity were older, had higher disease activity and more disability. Regardless of comorbidity, most patients were prescribed a tumour necrosis factor inhibitor (76%). The use of interleukin-17 inhibitors increased with comorbidity burden (0/1/≥2 comorbidities: 13%/18%/19%), whereas Janus kinase inhibitor use declined (2.3%/1.6%/0.8%). Retention rates were marginally lower with higher comorbidity burden (80%/76%/78%) (log-rank, p=0.036) and obesity (absent 79% vs present 77%) (log-rank, p=0.04). The risk of treatment withdrawal was only marginally higher in patients with higher comorbidity burden (one comorbidity: HR 1.19; 95% CI 1.02 to 1.40; ≥2 comorbidities: HR 1.18; 0.98 to 1.42).Conclusion Patients with cardiometabolic comorbidities had higher disease activity at treatment initiation of the first b/tsDMARD. Prescription patterns varied with comorbidity burden. Cardiometabolic comorbidity burden, especially obesity, was associated with marginally lower treatment retention.

OBJECTIVES:To explore the association between national socioeconomic indicators, and (i) 6/12/24-month retention of biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), and (ii) disease activity at treatment start, in patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA). METHODS:Longitudinal data from 13 European countries, including 38,911 patients with spondyloarthritis (17,296 PsA and 21,615 axSpA) initiating b/tsDMARDs in 2015-2021, were collected by the European Spondyloarthritis Research Collaboration Network. Kaplan-Meier, mixed-effects Cox regression, linear regression, and mixed models were used for comparisons across countries with low/medium/high national socioeconomic indicators (gross domestic product [GDP], Human Development Index [HDI], gross national income, current health expenditure, out-of-pocket expenditure), stratified by disease/b/tsDMARD number/sex. RESULTS:Drug retention was significantly lower in both men and women with PsA/axSpA from countries with high vs medium/low GDP per capita after 6/12/24 months' treatment with 1st/≥2nd b/tsDMARD (log rank P < .001). For all socioeconomic indicators, higher wealth was associated with earlier discontinuation of 1st b/tsDMARD both in PsA and axSpA men and women. The strength of associations varied across indicators, treatment lines, and sex. The strongest associations between socioeconomic measures and b/tsDMARD retention were seen with GDP per capita and HDI, and most prominently in women with axSpA. At the country level, most disease activity measures at the start of 1st/≥2nd b/tsDMARD were significantly worse with lower GDP, particularly for PsA. CONCLUSIONS:Treatment retention varies with countries' socioeconomic status. Clinicians and health policy makers should be aware of later discontinuation/switching of b/tsDMARDs and a tendency to higher country-level disease activity at b/tsDMARD initiation in lower-income countries.

Background Studies on national policies for biologics are warranted. Objectives To map and compare national healthcare set-ups for prescription, start, switch, tapering, and discontinuation of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with psoriatic arthritis and axial spondyloarthritis across Europe, and assess the healthcare set-ups in relation to countries’ socio-economic status. Methods An electronic survey was developed to collect and compare information on national healthcare systems. The relationship between the cumulative score of biologic/targeted synthetic DMARD regulations, socioeconomic indices, and biologic originator costs were assessed by linear regression. Results National healthcare set-ups differed considerably across the 15 countries, with significantly fewer regulations with increasing socioeconomic status measured by GDP/current health expenditure/human development index, and with increasing biologic originator costs. In most countries, the biologic/targeted synthetic DMARD prescribing doctor was required to adhere to country and/or hospital recommendations, and about a third of countries had a national/regional tender process. Prescription regulations for biologic/targeted synthetic DMARDs, including pre-treatment and disease activity requirements, varied substantially. Approximately a third of countries had criteria for discontinuation and tapering, whereas only few had for switching. Notably, two countries disallowed biologic/targeted synthetic DMARD retrials, and one imposed limit on the maximum number of biologic/targeted synthetic DMARDs permitted. Conclusion The findings highlight substantial variability in healthcare set-ups for biologic/targeted synthetic DMARD use in psoriatic arthritis and axial spondyloarthritis across Europe and their association with socioeconomic status and drug costs. These insights provide a basis for rheumatology societies, policymakers, and stakeholders to evaluate and potentially optimize healthcare policies.

Objective: To provide the first nationwide description of biologic and targeted synthetic DMARD (b/tsDMARD) use among Estonian patients with rheumatoid arthritis (RA), focusing on treatment effectiveness, persistence, and reasons for discontinuation across sequential lines of therapy. Methods: Data were obtained from the Estonian Biologic Therapy Registry covering years 2006–2022. All adult RA patients (ICD-10 M05.8, M06.0) who had received at least one dose of a b/tsDMARD were included. Effectiveness at 6 months was evaluated using DAS28-CRP as a continuous measure (ΔDAS28) and categorical response definitions: remission (DAS28 ≤2.6), low disease activity (LDA ≤3.2), and EULAR response criteria. Treatment persistence was analyzed using Kaplan–Meier estimates, and reasons for discontinuation were categorized systematically. Results: A total of 1,074 patients were analysed (78% female, mean age 53.7 years, 86% sero-positive). Mean baseline DAS28-CRP was 5.3. The mean 6-month reduction in DAS28-CRP during first-line therapy was ~2.3 points. Remission was achieved in ~20% of patients in lines 1–3 and ~15% in later lines, while LDA occurred in 7–10% across lines 1–4. Drug survival was comparable between treatment lines: 60% of patients remained on therapy at 2 years, and the median time to discontinuation for first-line therapy was 1.66 years. Most patients initiated therapy with a TNF inhibitor and many continued within the same class before switching to IL-6 inhibitors, rituximab, or JAK inhibitors. The main reasons for discontinuation were loss or lack of efficacy (~50%) and adverse events (27.5%), predominantly allergic reactions and infections. Conclusions: In real-world Estonian RA practice, biologic and targeted therapies were effective across multiple treatment lines, with the greatest improvement observed during first-line therapy and sustained clinical benefit in later lines. Treatment persistence remained stable despite multiple switches, and the distribution of discontinuation causes mirrored other European registries. These findings support the continued value of sequential b/tsDMARD therapy in achieving disease control among patients with difficult-to-treat RA.

OBJECTIVES:The Disease Activity index for Psoriatic Arthritis (DAPSA) was developed to assess disease activity in patients with psoriatic arthritis (PsA). A modified version, DAPSA28, uses 28 joints instead of 66/68. This study evaluated key psychometric properties of DAPSA and DAPSA28. METHODS:Data from 1865 patients with PsA in the European Spondyloarthritis (EuroSpA) Research Collaboration Network, having DAPSA and DAPSA28 scores at baseline and follow-up, were analysed. Tests included assessment of internal construct validity by scree plots, confirmatory factor analysis (CFA) and structural equation modelling (SEM), supplemented by tests of differential item functioning (DIF) and evaluation of internal consistency reliability by Cronbach's α (CA). A subset of 625 patients was used for most analyses, except descriptive statistics, correlation matrix and CA. RESULTS:One-dimensional CFA models for DAPSA and DAPSA28 showed acceptable model fit at baseline (root mean square error of approximation, RMSEA: 0.020, 0.034). However, model fit at 6 months follow-up was poor (RMSEA: 0.057, 0.063). SEM combining baseline and follow-up data could not identify an acceptable model fit. DIF was found for sex and country. CA indicated acceptable internal consistency (DAPSA: 0.65; DAPSA28: 0.63). Heterogeneity across countries was observed. CONCLUSIONS:Overall, the model fit was acceptable across model fit statistics, supporting internal construct validity, but some evidence of misfit at country level was disclosed. Our findings support acceptable internal consistency reliability, but DIF was found for sex and country. Based on mixed results of model fit and DIF, further investigation of these and other PsA disease activity measures is warranted.

What does this mean for patients?People with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) often have many other health issues. These issues may affect their arthritis treatment, but we do not know how. To study this, we first need to know what data there are. Are these health issues being recorded in the clinics? This might be in local or national registries. We also need to know if different registries record data in similar ways. If they do, researchers can gather more information on the same health issues from many registries. We surveyed 17 registries in Europe to determine this. We asked if, and how, they record data on 58 health issues. We found that heart disease, gut disease, infections, psoriasis and uveitis are regularly recorded. Many registries used similar methods to record data. Our findings can help to pave the way for future research, leading to better treatment strategies for people with PsA and axSpA.

Background: In comparative effectiveness research, treatment retention - i.e., the time from treatment start to treatment discontinuation - is an important indicator of treatment effectiveness for chronic illnesses. There is no agreement on the event that defines discontinuation. Commonly used are “last dose received”, “decision to discontinue”, or “first dose missed”, as well as mixtures of these in multi-source studies. For drugs administered less frequently than once daily as is the case for many disease-modifying anti-rheumatic drugs (DMARDs) used for the treatment of spondyloarthritis, retention as determined by these events can vary considerably. Our goal was to quantify the impact of the different definitions of discontinuation on conclusions drawn from treatment comparisons and to recommend a standardised definition. Methods: We utilised model-based simulations and real-world data from spondyloarthritis patients treated with tumour necrosis factor (TNF) inhibitors, DMARDs with a wide range of dosing intervals, in Europe. We compared the estimation of the hazard ratio of discontinuation between treatments with varying differences in dosing intervals for the different definitions of discontinuation. To accommodate interval-censored events we used linear transformation models. Results: The simulation revealed increasing differences in the estimated treatment hazard ratio based on time to “last dose received” or “first dose missed” compared to “decision to discontinue” with increasing differences in the dosing interval (up to 55 days). These differences were, however, small and further diminished with mixed events. No bias was observed when the time to “decision to discontinue” was analysed as interval-censored between the times to “last dose received” and “first dose missed” instead of as exactly observed. No clinically meaningful differences in estimated hazard ratios between TNF inhibitors with different dosing intervals (56 versus 7 days) were observed in the real-world data. Conclusions: The impact of the different treatment discontinuation definitions on comparative retention were found to be negligible. Nonetheless, we recommend to define retention as the time from treatment start to the decision to discontinue treatment. Is the timing of the decision unknown, retention can be analysed as interval-censored between the last dose received and the first dose missed using transformation models. Trial registration: Not applicable.

Objectives This study aimed to (1) to describe trends of tranquilliser and sedative (TS) misuse in Estonia during 2003–2019 and (2) to analyse the associations between TS misuse and explanatory factors (perceived access to TS, medical use of TS, family-related, friends-related, school-related factors, risk behaviour and leisure time physical activity).Design A cross-sectional study.Setting Data were collected from the European School Survey Project on Alcohol and Other Drugs (ESPAD) from 2003 to 2019 in Estonia.Participants Estonian schoolchildren aged 15–16 years old (n=11 328), 48.6% were boys.Outcome measures Prevalence, crude and adjusted ORs with 95% CIs for TS misuse.Results The prevalence of lifetime TS misuse significantly increased from 2003 (5.0% of boys and 12.6% of girls) to 2019 (11.3% and 17.5%, respectively) (p<0.001). Among boys, TS misuse increased significantly among those reporting medical use of TS from 21.1% to 41.4% in 2003–2019 (p=0.006). Medical use of TS multiplied the odds of misuse by 6.89 (95% CI 5.15 to 9.24) for boys and by 4.53 (95% CI 3.58 to 5.73) for girls. Perceived easy access to TS increased the odds of misuse by 6.57 (95% CI 4.13 to 10.46) times for boys and by 4.66 (95% CI 3.25 to 6.70) times for girls. Having many friends who misuse TS increased the odds of misuse by 3.27 (95% CI 2.16 to 4.95) times for boys and by 5.07 (95% CI 3.79 to 6.77) times for girls. Furthermore, higher odds of TS misuse were observed among adolescents who smoked cigarettes and engaged in less sports.Conclusions TS misuse prevalence among Estonian adolescents increased significantly from 2003 to 2019. Misuse was strongly associated with medical use, perceived easy access and friends’ TS misuse. These findings emphasise the need for targeted prevention strategies, including improving prescription practices, limiting TS access and promoting healthy behaviours and positive peer relationships among adolescents.

Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24 -month patient -reported outcomes (PRO) remission and the 24 -month retention rates. Patients and methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) <= 2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) <= 0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan -Meier plots with log -rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. Results: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24 -month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02]). Conclusion: In this large European real -world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.

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 n 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.

Background Excess all-cause mortality is a key indicator for assessing direct and indirect consequences of injection drug use and data are warranted to delineate sub-populations within people who inject drugs at higher risk of death. Our aim was to examine mortality and factors associated with mortality among people who inject drugs in Estonia.Methods Retrospective cohort study using data from people who inject drugs recruited in the community with linkage to death records. Standardized mortality ratios were used to compare the cohort mortality to the general population and potential predictors of death were examined through survival analysis (Cox regression). The cohort include a total of 1399 people who inject drugs recruited for cross-sectional surveys using respondent driven sampling between 2013 and 2018 in Estonia. A cohort with follow-up through 2019 was formed with linkage to national causes of death registry.Results Among 1399 participants with 4684 person-years of follow-up, 10% were deceased by 2019. The all-cause mortality rate in the cohort was 28.9 per 1000 person-years (95% confidence interval 25.3-35.3). Being HIV positive, injecting mainly opioids (fentanyl), living in the capital region and the main source of income other than work were associated with greater mortality risk.Conclusions While low-threshold services have been available for a long time for people who inject drugs, there is still a need to widen the availability and integration of services, particularly the integration of HIV and opioid treatment.

IntroductionObtaining epidemiological data on chronic hepatitis C virus (HCV) infection is essential to monitor progress towards the hepatitis C elimination targets.AimWe aimed to estimate the prevalence of chronic HCV and the seroprevalence of HCV in the adult general population in Estonia.MethodsThis cross-sectional study, conducted between 12 July and 6 December 2022, included anonymised residual sera collected prospectively from patients 18 years and older visiting a general practitioner in all counties of Estonia. Specimens were considered HCV-seropositive if they tested positive for HCV antibodies by enzyme-linked immunoassay, confirmed by line-immunoblot assay. Chronic HCV infection was determined by positive RT-qPCR.ResultsWe tested a total of 4,217 specimens. The estimated HCV seroprevalence and prevalence of chronic HCV infection were 1.8% (95% CI: 1.4-2.2) and 0.8% (95% CI: 0.5-1.1), respectively, with ca 8,100 persons estimated to have chronic HCV infection in the general adult population of Estonia. No statistically significant differences in the prevalence of chronic HCV infection were observed between sexes, counties or age groups, with the highest prevalence rates observed in men (sex ratio: 1.7), Ida-Virumaa County (1.8%; 95% CI: 0.8-3.6) and the age group 40-49 years (1.7%; 95% CI: 0.9-2.9).ConclusionThis study found an overall low prevalence of chronic HCV infection in Estonia. Continued efforts should be made for the targeted screening, diagnosis and treatment of individuals with chronic HCV infection to achieve hepatitis elimination targets.

Objectives: In axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating secukinumab, we aimed to assess retention rates and proportions of patients achieving remission and low disease activity (LDA), according to disease activity measures and patient-reported outcomes at 24 and 48 months.Patients and methods: Data on patients with axSpA and PsA who initiated secukinumab treatment were pooled from 13 European registries. Analyses were performed overall and stratified according to the number of previous biologic/targeted synthetic Disease-Modifying Antirheumatic Drugs (b/tsDMARDs, 0/1/≥ 2). Kaplan-Meier plots and Cox regression analyses were performed to assess and compare secukinumab retention rates. Comparisons of remission and LDA rates were performed by logistic regression analyses.Results: The overall 24-/48-month secukinumab retention rates were 61%/51% in 767 axSpA patients, and 64%/49% in 975 PsA patients, respectively. Compared to b/tsDMARD naïve patients, a higher risk of withdrawal from secukinumab was found for those with ≥ 2 prior b/tsDMARDs in axSpA and PsA, and 1 prior b/tsDMARD in axSpA. Generally, remission and LDA rates were numerically higher in b/tsDMARD naïve patients. After adjustment for confounders, statistically significantly higher remission and LDA rates were found for b/tsDMARD naïve patients compared to patients with ≥ 2 prior b/tsDMARDs at 24 months in axSpA and PsA.Conclusion: This large European real-world study demonstrates that 4-year secukinumab retention rates were approximately 50% in both axSpA and PsA. b/tsDMARD naïve patients had higher retention, remission and LDA rates than patients with prior b/tsDMARD exposure.