Exploring disease-related and treatment-related issues and concerns experienced by adults with spondyloarthritis, inflammatory bowel disease and psoriasis to identify unmet needs: a qualitative clinical concept mapping study.

OBJECTIVES: Exploring patients' perspectives for significant factors of relevance in living with a chronic disease is important to discover unmet needs and challenges. The primary objective of this study was to explore disease-related and treatment-related issues and concerns experienced by adults with spondyloarthropathies (SpA) and associated diseases. As a secondary objective, we wanted to explore whether these factors were generic or disease dependent. DESIGN: We used group concept mapping (GCM), a validated qualitative method, to identify disease-related and treatment-related issues and concerns. Participants generated statements in the GCM workshops and organised them into clusters to develop concepts. Furthermore, participants rated each statement for importance from 1: 'not important at all' to 5: 'of great importance'. SETTING: Participants were recruited during routine care at the outpatient clinic at the hospitals in the period from May 2018 to July 2022. PARTICIPANTS: Eligible participants were adults ≥18 years and diagnosed with axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), psoriasis (PsO) or inflammatory bowel disease -split into Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: 52 patients participated in the 11 workshops divided into groups according to their diagnosis. They created a total of 1275 statements that generated 10 AxSpA concepts, 7 PsA concepts, 7 PsO concepts, 10 CD concepts and 11 UC concepts. The highest rated concepts within each disease group were: AxSpA, 'lack of understanding/to be heard and seen by healthcare professionals' (mean rating 4.0); PsA, 'medication (effects and side effects)' (mean rating 3.8); PsO, 'social and psychological problems, the shame' (mean rating 4.0); CD, 'positive attitudes' (mean rating 4.3) and UC; 'take responsibility and control over your life' (mean rating 4.0). CONCLUSION: People with SpA and associated diseases largely agree on which concepts describe their disease-related and treatment-related issues and concerns with a few of them being more disease-specific.

Tolerability and comparative effectiveness of TNF-, IL-17-, and IL-23(p19) inhibitors in psoriatic arthritis: A target trial emulation study.

OBJECTIVES: To compare tolerability and effectiveness of two different classes of biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs; interleukin (IL)-17- and IL-23(p19) inhibitors) relative to tumour necrosis factor inhibitors (TNFi) regarding the drug survival rates and treatment outcomes in patients with psoriatic arthritis (PsA). METHODS: We emulated a target trial on comparative effectiveness using observational data from a prospective cohort study based on the Parker Institute's PsA cohort - the PIPA cohort. All patients underwent interview and clinical examination programme at baseline and at follow-up visits at four and twelve months. The primary endpoint, drug survival, was assessed up to 12 months from baseline. We estimated hazard ratios from proportional hazards model and used propensity score adjustment in an attempt to deconfound and emulate a random treatment assignment. RESULTS: We included a total of 109 patients in the intention-to-monitor population at baseline initiating either TNFi (75 patients), IL17i (26 patients), or IL23(19)i (8 patients). Hazard ratios in the propensity adjusted model comparing IL-17i and IL-23(p19)i to TNFi were 1.36 (95% CI 0.59-3.14) and 0.56 (95% CI 0.10-3.24), respectively. TNFi and IL-17i had comparable effects regarding response rates and changes in clinical outcomes after 12 months, whereas IL-23(p19)i tended to perform better overall. CONCLUSION: No decisive differences between drugs were observed at group level regarding drug survival and clinical outcomes after 12 months. TNFi, IL-17i, and IL-23(p19)i may all be considered equally effective in the treatment of patients with PsA, advocating for investigating more in personalised treatment strategies.

Types of kindergarten and their relationship with parental and children's socio-demographic characteristics in Denmark.

In Danish outdoor kindergartens, children are spending most of the day outdoors often in forests or similar nature environments. These children are assumed to be healthier than children attending conventional kindergartens, however, factors related to choosing a specific type of kindergarten may explain the differences. To better understand this, we aimed to investigate parents reasons for choosing either outdoor or conventional kindergartens based on a mixed-method participatory Concept Mapping approach, and further if parental socio-demographics and early child characteristics differed prior to enrolling children to either type of kindergarten using a cohort register-based approach. Parents of children attending outdoor kindergartens (n = 23) weighed reasons such as "physical setting, outdoor life, and freedom of movement" high, whereas "a good first impression of the kindergarten" was an important reason for parents choosing a conventional kindergarten (n = 22). In the register-based approach, 2434 and 2643 children attended outdoor or conventional kindergartens, respectively. The parents choosing outdoor kindergartens as well as their children differed according to most investigated characteristics, including origin (maternal non-Western: 4.2% vs. 21.9%, p < .0001), educational level (maternal long education: 45.6% vs. 33.0%, p < .0001), prematurity (5.1% vs. 7.1%, p = 0.004) and sex (females: 43.5% vs. 48.6%, p = <0.0013). In conclusion, parental reasons for choosing kindergarten as well as parental socio-demographics differed substantially among kindergarten type. These differences might cause selection bias if not considering when comparing health outcomes among children attending different kinds of kindergartens.

Identifying and understanding disease burden in patients with inflammatory bowel disease.

OBJECTIVE: Physicians tend to focus on biomedical targets while little is known about issues important to patients. We aimed to identify critical concepts impacting patients with inflammatory bowel disease (IBD). DESIGN: We performed a survey of patients with IBD in biologic therapy (n=172) and used a validated qualitative method called group concept mapping (GCM) in patient workshops. The survey included 13 questions on attitudes toward symptoms and issues related to IBD. In the eight workshops, patients (n=26) generated statements later clustered into concepts identifying issues impacting a patient's life. Patients ranked the statements. RESULTS: In the survey, patients' mean age were 40 years (SD 13), 53% were women, and 38% had ulcerative colitis. They identified fatigue (57%) and stool frequency (46%) as the most critical symptoms impacting their daily lives regardless of disease activity. In the GCM workshops with Crohn's disease (n=13) (median age 42 years (IQR 39-51) and 62% were women), 335 statements divided among 10 concepts were generated, and the three most important concepts were 'Positive attitudes', 'Accept and recognition', and 'Sharing knowledge and experiences in life with Crohn's disease'. In the workshops with ulcerative colitis (n=13) (median age 43 years (IQR 36-49) and 69% were women), 408 statements divided into 11 concepts were generated; the most important concepts were 'Take responsibility and control over your life', 'Medication', and 'Everyday life with ulcerative colitis'. CONCLUSION: Focusing solely on IBD symptoms, patients identified fatigue and stool frequency to impact daily life the most. However, when investigating the disease burden in a broader perspective beyond classic IBD symptoms, patients identified concepts with focus on emotional health to be most important. TRIAL REGISTRATION: The Copenhagen University Hospital, Herlev and Gentofte approved the questionnaire and methodology (work-zone no: 18015429).

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics.

BACKGROUND: Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy. METHODS: Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue. RESULTS: Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies. CONCLUSION: Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses.

OBJECTIVE: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. METHODS: This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj ] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). RESULTS: In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. CONCLUSION: Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.

The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries.

OBJECTIVES: In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). METHODS: Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3, ≥4 or ≥5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009-2011, 2012-2013, 2014-2015, 2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. RESULTS: Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009-2015, whereof proportions treated with ≥3, ≥4 or ≥5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. CONCLUSION: In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.

Effectiveness of a Second Biologic After Failure of a Non-tumor Necrosis Factor Inhibitor As First Biologic in Rheumatoid Arthritis.

OBJECTIVE: In rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non-tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. METHODS: We identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months). RESULTS: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%). CONCLUSION: The drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

Relation Between Fatigue and ACR Response in Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitor Therapy: A Population-based Cohort Study.

OBJECTIVE: The objective of this population-based cohort study was to investigate the association between fatigue with disease activity and drug survival in patients with psoriatic arthritis (PsA) receiving their first tumor necrosis factor inhibitor (TNFi). METHODS: Data on patient characteristics, disease activity, and drug survival were obtained from the DANBIO database on all patients with PsA from 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry. RESULTS: A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measures (Disease Activity Score in 28 joints based on C-reactive protein), pain, and Health Assessment Questionnaire (HAQ) scores; tender joint counts; comorbidities (Charlson Comorbidity Index ≥ 2); and current smoking status at baseline compared to patients with lower median fatigue scores (P < 0.05). In the upper median fatigue group, fewer patients achieved American College of Rheumatology (ACR) responses and improvements in visual analog scale (VAS) fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month follow-up. CONCLUSION: Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain, and HAQ scores; more comorbidities; and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate, suggesting heterogeneity between experienced fatigue and joint inflammation.

Incentives for Danish healthcare management based on a pilot outcome-based, patient-centric management model in psoriasis and psoriatic arthritis: the non-interventional IMPROVE study.

BACKGROUND: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic diseases that affect patients' quality of life. The purpose of the present study was to develop a pilot outcome-based, patient-centric management model for PsO and PsA. METHODS: The non-interventional IMPROVE (Incentives for healthcare management based on patient-related outcomes and value) study being conducted in Denmark consists of 5 phases: 1) collecting real-world evidence to estimate treatment patterns and disease burden to the healthcare sector and patients; 2) identifying disease aspects which matter most to patients by use of concept mapping; 3) conducting interviews with healthcare professionals and patient organization involved in a typical PsO or PsA patient journey in order to determine relevant measures to quantify patient-identified outcomes; 4) developing a value-based remuneration model based on outcomes from phases 1-3; and 5) testing the outcome-based model in pre-selected hospitals in Denmark. RESULTS: Both PsO and PsA are associated with multiple co-morbidities, increased healthcare costs, and loss of earnings. Seven important 'clusters' of disease aspects were identified for both PsO and PsA, including uncertainty about disease progression and treatments, as well as inter-personal relations with healthcare providers. Hospital-based treatment was associated with high treatment costs. Although the outcome-based model could result in strategic behavior by doctors, those involved in defining the best outcome goals consider it unlikely. CONCLUSION: The new patient-centric outcome-based management model is expected to support optimal treatment and secure best possible outcomes for patients suffering from PsO or PsA. The practical implication of the present study are that the models developed are expected to increase focus on patient-centered healthcare, and help eliminate some of the inappropriate incentives that exist in activity-based remuneration systems. TRIAL REGISTRATION: Not applicable; data collected from patient registries in Denmark.

Relationship Between Fatigue and Inflammation, Disease Duration, and Chronic Pain in Psoriatic Arthritis: An Observational DANBIO Registry Study.

OBJECTIVE: Fatigue is one of the most significant symptoms, and an outcome of great importance, in patients with psoriatic arthritis (PsA), but associations between underlying components of fatigue experienced by patients in relation to the disease have been sparsely investigated. The objectives were to describe the degree of fatigue in patients with PsA, and to examine important components associated with fatigue. METHODS: We performed a cross-sectional survey including patients registered in the Danish nationwide registry DANBIO from December 2013 to June 2014. Principal component analysis (PCA) was used to identify factors associated with fatigue. RESULTS: A total of 1062 patients with PsA were included in the study. A PCA reduced co-variables into 3 components explaining 63% of fatigue in patients. The first component, contributing to 31% of fatigue, was composed of inflammatory factors including swollen and tender joints, physician's global assessment, elevated C-reactive protein (CRP), and high Pain Detect Questionnaire (PDQ) score. The second component, contributing to 17% of fatigue, consisted of increasing age and long disease duration. The third component, contributing to 15% of fatigue, consisted of high PDQ score, tender joint count, increasing age, and concomitant low CRP, suggestive of a chronic pain component consisting of central pain sensitization or structural joint damage. CONCLUSION: Fatigue in patients with PsA may be driven by clinical inflammatory factors, disease duration, and chronic pain in the absence of inflammation.

Protocol for evaluating and implementing a pragmatic value-based healthcare management model for patients with inflammatory arthritis: a Danish population-based regional cohort and qualitative implementation study.

INTRODUCTION: The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing 'value-based healthcare' defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow's healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare. AIMS: The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care. METHODS AND ANALYSIS: Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement. ETHICS AND DISSEMINATION: The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers: the Nordic example.

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data.

Impact of Comorbidities on Tumor Necrosis Factor Inhibitor Therapy in Psoriatic Arthritis: A Population-Based Cohort Study.

OBJECTIVE: The objective of this population-based cohort study was to investigate the impact of comorbidities on disease activity, treatment response, and persistence with the first-tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA). METHODS: Data on patient characteristics, disease activity, and treatment response and persistence were obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register. Kaplan-Meier plots and Cox proportional hazard regression analyses were performed. Percentages of patients achieving relevant clinical responses were calculated. RESULTS: We identified 1,750 patients eligible for analyses. Patients with higher CCI scores had higher disease activity measures at baseline and increased occurrence of depression and/or anxiety. Kaplan-Meier curves showed shorter persistence with treatment for patients with a CCI score ≥2 (log-rank P < 0.001) and for patients with depression and/or anxiety (P = 0.027) compared to patients without comorbidities. In multivariate analysis, a CCI score ≥2 was associated with reduced TNFi persistence compared with patients without comorbidities (hazard ratio 1.72 [95% confidence interval 1.26-2.37]; P = 0.001). A smaller proportion of patients with a CCI score ≥2 achieved European League Against Rheumatism (EULAR) good response (P < 0.001) and EULAR good-or-moderate response (P < 0.001) at 6 months compared with patients without comorbidities. CONCLUSION: The presence of comorbidities was associated with higher baseline disease activity, shorter TNFi persistence, and reduced clinical response rates in a cohort of Danish patients with PsA.

Work Disability in Newly Diagnosed Patients with Primary Sjögren Syndrome.

OBJECTIVE: To study longterm work disability and possible predictors in newly diagnosed patients with primary Sjögren syndrome (pSS). METHODS: Because we wanted to include only patients with full work availability potential, eligible patients were aged 18-62 years. Fifty-one patients (mean age 46 yrs, range 18-61 yrs, 50 women) diagnosed with pSS between January 2001 and December 2012 were included in the study. For each patient we randomly selected 4 reference subjects from the general population and matched for age, sex, and area of residence. We linked data to the Swedish Social Insurance Agency and calculated the proportion as well as net days of work disability in 30-day intervals from 12 months before pSS diagnosis until 24 months after . RESULTS: Work disability was increased in patients with pSS in comparison to general population comparators. At diagnosis, 26% of patients were work-disabled, while 37% and 41% were disabled at 12 and 24 months after diagnosis, respectively (p < 0.05 and p < 0.05 vs baseline). Prior work disability status at diagnosis (OR 15.4, 95% CI 2.9-81.9; p = 0.001), concomitant fibromyalgia (OR 10.5, 95% CI 2.0-56.0; p = 0.006), and each additional year of age (OR 1.1, 95% CI 1.0-1.2; p = 0.009) were found to be associated with work disability 24 months after diagnosis. CONCLUSION: Patients with pSS showed an increased work disability, in comparison with the general population, which increased significantly during the first 2 years after diagnosis. Work disability at diagnosis, concomitant fibromyalgia, and increasing age, but not anti-SSA/anti-SSB antibodies or disease activity, were associated with longterm work disability.

EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy: A prospective observational study of patients registered in the south Swedish SSATG registry.

OBJECTIVES: Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-to-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. MATERIALS AND METHODS: All RA patients registered in a regional database as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from 1st of January 2006 through 31st of December 2012, were included. Patients were followed from initiation of the first dose of bDMARD monotherapy treatment until withdrawal from treatment, loss of follow-up or 31st of December 2012. Descriptive statistics for utility (EQ-5D-3L), effectiveness, and drug survival of bDMARD monotherapy were calculated. RESULTS: During the study period, a total of 554 patients were registered in SSATG as initiating bDMARD monotherapy. Most of the patients were women (81%), with a mean age of 57 years. The average disease duration was more than 12 years, and on average the patients had previously been treated with approximately four different csDMARDs. Fifty-five percent of the patients were initiating their first bDMARD, 26% their second, and 19% their third or more. At baseline the average EQ-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months´ follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences between type of bDMARD (p = 0.49). The mean change in EQ-5D-3L ranged from 0.11 (rituximab and infliximab) to 0.42 (tocilizumab). Although the changes were numerically different, no distinct pattern favored any particular bDMARD for EQ-5D-3L (p = 0.49) or other clinical outcomes. Overall, DAS28 defined remission and low disease activity were achieved in 20% and 43% of patients, respectively. Drug survival rates were statistically significantly different between bDMARDs (p = 0.01), with the highest rates observed for rituximab, followed by etanercept. After failing first course of anti-TNF, patients switching to another mode of action had significantly higher drug survival than those switching to a second course of anti-TNF therapy (p = 0.02). CONCLUSIONS: Utility (EQ-5D-3L) increased after 6 months of all bDMARD treatments in monotherapy, indicating improvement of patients' quality of life. After failure of anti-TNF treatment in monotherapy, switching to another mode of action may be associated with better drug survival than starting a second TNF-inhibitor.

Effectiveness and drug adherence of biologic monotherapy in routine care of patients with rheumatoid arthritis: a cohort study of patients registered in the Danish biologics registry.

OBJECTIVES: To estimate the prevalence of Danish RA patients currently on biologic monotherapy and compare the effectiveness and drug adherence of biologic therapies applied as monotherapy. METHODS: All RA patients registered in the Danish biologics database (DANBIO) as receiving biologic DMARD (bDMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics for prevalence, effectiveness and drug adherence of bDMARD monotherapy were calculated. RESULTS: Of the 775 patients on bDMARD monotherapy, adalimumab (21.3%), etanercept (36.6%) and tocilizumab (15.3%) were the most prevalent biologic agents administered. At the 6-month follow-up, the overall crude clinical disease activity index remission rate in patients still on a biologic drug was 22%, the 28-joint DAS remission rate was 41% and the response rate of those with a 50% improvement in ACR criteria was 28%. At the 6-month follow-up, the drug adherence rates were similar for the different bDMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P < 0.001). The overall drug adherence (except for infliximab) was approximately 70% after 2 years. CONCLUSION: Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.

The dynamics of the pain system is intact in patients with knee osteoarthritis: An exploratory experimental study.

Background and aims Despite the high prevalence of knee osteoarthritis (OA) it remains one of the most frequent knee disorders without a cure. Pain and disability are prominent clinical features of knee OA. Knee OA pain is typically localized but can also be referred to the thigh or lower leg. Widespread hyperalgesia has been found in knee OA patients. In addition, patients with hyperalgesia in the OA knee joint show increased pain summation scores upon repetitive stimulation of the OA knee suggesting the involvement of facilitated central mechanisms in knee OA. The dynamics of the pain system (i.e., the adaptive responses to pain) has been widely studied, but mainly from experiments on healthy subjects, whereas less is known about the dynamics of the pain system in chronic pain patients, where the pain system has been activated for a long time. The aim of this study was to assess the dynamics of the nociceptive system quantitatively in knee osteoarthritis (OA) patients before and after induction of experimental knee pain. Methods Ten knee osteoarthritis (OA) patients participated in this randomized crossover trial. Each subject was tested on two days separated by 1 week. The most affected knee was exposed to experimental pain or control, in a randomized sequence, by injection of hypertonic saline into the infrapatellar fat pad and a control injection of isotonic saline. Pain areas were assessed by drawings on anatomical maps. Pressure pain thresholds (PPT) at the knee, thigh, lower leg, and arm were assessed before, during, and after the experimental pain and control conditions. Likewise, temporal summation of pressure pain on the knee, thigh and lower leg muscles was assessed. Results Experimental knee pain decreased the PPTs at the knee (P <0.01) and facilitated the temporal summation on the knee and adjacent muscles (P < 0.05). No significant difference was found at the control site (the contralateral arm) (P =0.77). Further, the experimental knee pain revealed overall higher VAS scores (facilitated temporal summation of pain) at the knee (P < 0.003) and adjacent muscles (P < 0.0001) compared with the control condition. The experimental knee pain areas were larger compared with the OA knee pain areas before the injection. Conclusions Acute experimental knee pain induced in patients with knee OA caused hyperalgesia and facilitated temporal summation of pain at the knee and surrounding muscles, illustrating that the pain system in individuals with knee OA can be affected even after many years of nociceptive input. This study indicates that the adaptability in the pain system is intact in patients with knee OA, which opens for opportunities to prevent development of centralized pain syndromes.

Intra-Articular Analgesia and Steroid Reduce Pain Sensitivity in Knee OA Patients: An Interventional Cohort Study.

Objectives. To assess the effects of intra-articular therapy on pain sensitivity in the knee and surrounding tissues in knee OA patients. Methods. Twenty-five knee OA patients with symptomatic knee OA were included in this interventional cohort study. Pressure pain thresholds (PPT) were recorded before, immediately after, and two weeks after ultrasound guided intra-articular injection of lidocaine combined with glucocorticosteroid. Computer-controlled and manual pressure algometers were used to assess PPT on the knee, vastus lateralis, tibialis anterior, and the extensor carpi radialis longus muscles (control site). Results. Significantly increased PPTs were found following intra-articular injection, at both the knee (P < 0.0001) and the surrounding muscles (P < 0.042). The treatment effects were sustained for two weeks, and at some points the effect was even greater at two weeks (P < 0.026). Albeit not statistically significant, a similar trend was observed at the control site. Conclusions. Intra-articular anesthesia, combined with glucocorticosteroid, reduced pain sensitivity in both the knee and surrounding muscles for at least two weeks.