Search

Objectives To compare the tolerability and effectiveness of two different classes of biological DMARDs [IL-17 and IL-23(p19) inhibitors, IL-17i and IL-23(p19)i] relative to TNF inhibitors (TNFi) regarding the drug survival rates and treatment outcomes in patients with 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 a clinical examination programme at baseline and at follow-up visits at 4 and 12 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), IL-17i (26 patients) or IL-23(19)i (8 patients). Hazard ratios in the propensity adjusted model comparing IL-17i and IL-23(p19)i with 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 personalized treatment strategies., 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.

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).

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.

Objectives: To explore the prognostic value of pre-specified comorbidities on treatment outcomes in PsA, and to compare baseline data with cutaneous psoriasis without arthritis and healthy controls (HC). Methods: Patients initiating conventional synthetic/biological disease-modifying antirheumatic drugs were enrolled in this clinical observational cohort study, and data on comorbidities, and clinical and patient-reported outcomes were retrieved at baseline and after 4 months. Pearson's chi-squared tests were performed to investigate the prognostic value of pre-specified comorbidities and achievement of ACR20, DAPSA50 and MDA. Mann-Whitney U tests were used to compare OMERACT PsA Core Outcome Set (COS) measures at baseline and follow-up for the pre-specified comorbidities. Results: A total of 100 PsA patients were included at baseline. Statistically significantly fewer patients with obesity achieved DAPSA50 compared with patients without obesity (P =0.035), and fewer patients with hypertension (P =0.034) and Charlson Comorbidity Index (CCI) ≥1 (P =0.027), respectively, achieved MDA compared with patients without these comorbidities. Patients with obesity, hypertension, widespread pain, and CCI ≥1 had significantly worse COS measures at follow-up compared with patients without these comorbidities. At baseline, patients with PsA had higher disease burden compared with patients with cutaneous psoriasis and HC, including higher pain (P <0.001) and fatigue (P <0.001) scores, and more widespread pain (P =0.002). Conclusion: Obesity, hypertension and CCI ≥1 were prognostic factors for poorer treatment outcome rates in PsA. Pain and fatigue were more frequently reported among patients with PsA compared with patients with cutaneous psoriasis and HC. Trial registration: The Danish National Committee on Health Research Ethics: H-15009080; Data Protection Agency: 2012-58-0004; ClinicalTrials.gov: NCT02572700.

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.

PURPOSE: Optic disc drusen (ODD) are calcified optic nerve head deposits. Objectives of this study were to examine the prevalence of ODD in eyes removed by enucleation and to describe related histopathological signatures of ODD and surrounding tissues.METHODS: The study was a retrospective observational case series study assessing and re-evaluating enucleated eyes in Denmark from 1980 to 2015 by microscopy. Individual ODD were described based on size, number and location (superficial and/or deep) within the optic nerve. Optic nerve heads with ODD were assessed for elevated discs, retinal nerve fibre layer (RNFL) thickness, oedematous axons and presence of localized peripapillary axonal distension (LPAD) equivalent to the peripapillary hyperreflective ovoid mass-like structures seen on optical coherence tomography.RESULTS: Microscopy of 1713 eyes revealed ODD in 31 eyes equivalent to a prevalence of 1.8%. Optic disc drusen (ODD) were seen as circular shapes of different sizes and varying number. Elevated discs were present in 15 (54%) of the cases. Thickening of the superficial RNFL was present in eyes with large deeply located ODD. For more superficial ODD of approximately same size, the RNFL was thinner. Oedematous axons were present in three eyes. Localized peripapillary axonal distension (LPAD) was seen in five eyes.CONCLUSIONS: Prevalence of ODD in this study of histopathological signatures was higher than the prevalence found in clinical studies. Our results suggest that large, deep ODD might cause crowding and herniation of axons in the optic nerve head leading to a thickened superficial nerve fibre layer, pseudopapilledema and LPAD.

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.

OBJECTIVE: To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease.METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs.RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility criteria "targeted therapy history," "minimum required disease duration," "required negative rheumatoid factor," and "required Classification Criteria for Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time-point-of-retention reporting (adaptive trials).CONCLUSION: From this exploratory meta-epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.

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 was 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 1750 patients eligible for analyses. Patients with higher CCI 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 ≥ 2 CCI (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, [1.26 to 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: 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. This article is protected by copyright. All rights reserved.

BACKGROUND AND OBJECTIVE: Qualitative methods such as semi-structured interviews and focus-groups are used to evaluate the applicability and relevance of device technologies in clinical practice, but when used alone, often lack generalizability. This study aimed to assess the face validity and feasibility of using a composite, three-step qualitative method (the Parker Model), to inform the development and implementation of ava®, an electromechanical device (e-Device) for subcutaneous self-administration of the biologic, certolizumab pegol (CZP), used to treat rheumatic diseases.METHODS: The Parker Model combines concept mapping (CM), participatory design (PD), and stakeholder evaluation (SE). CM, a structured group process, was used to identify patients' opinions and concerns regarding the e-Device. Patients used this information in iterative PD sessions to create personal e-Device prototypes in cooperation with a designer and a healthcare professional. SE was performed based on semi-structured group and individual interviews with patients and disease-management stakeholders.RESULTS: The study recruited 14 patients, two doctors, two nurses, one medical secretary, and four other public servants. Three CM workshops revealed four key considerations: technical usability, physical design, concerns, and enthusiasm. Four personalized prototypes were developed during PD sessions. SE confirmed that the identified considerations were pivotal for the implementation and adaptation of the e-Device.CONCLUSIONS: This study is the first to apply a composite, qualitative research model when introducing an e-Device for the treatment and management of rheumatic disease. Results show that input from patients and other stakeholders using the Parker Model can add value to the development and implementation of an e-Device.

BACKGROUND: The development of digital health solutions for current health care settings requires an understanding of the complexities of the health care system, organizational setting, and stakeholder groups and of the underlying interplay between stakeholders and the technology. The digital health solution was founded on the basis of an information and communication technology platform and point-of-care devices enabling home-based monitoring of disease progression and treatment outcome for patients with rheumatoid arthritis (RA).OBJECTIVE: The aim of this paper is to describe and discuss the applicability of an iterative evaluation process in guiding the development of a digital health solution as a technical and organizational entity in three different health care systems.METHODS: The formative evaluation comprised the methodologies of contextual understanding, participatory design, and feasibility studies and included patients, healthcare professionals, and hardware and software developers. In total, the evaluation involved 45 patients and 25 health care professionals at 3 clinical sites in Europe.RESULTS: The formative evaluation served as ongoing and relevant input to the development process of the digital health solution. Through initial field studies key stakeholder groups were identified and knowledge obtained about the different health care systems, the professional competencies involved in routine RA treatment, the clinics' working procedures, and the use of communication technologies. A theory-based stakeholder evaluation achieved a multifaceted picture of the ideas and assumptions held by stakeholder groups at the three clinical sites, which also represented the diversity of three different language zones and cultures. Experiences and suggestions from the patients and health care professionals were sought through participatory design processes and real-life testing and actively used for adjusting the visual, conceptual, and pract