Gastrointestinal adverse drug reaction profile of etanercept:Real world data from patients and healthcare professionals

Objective. We aimed to describe the nature and frequency of gastrointestinal adverse drug reactions (GI-ADRs) of etanercept (ETN) using patient-reported and healthcare professional (HCP)-registered data and compared this frequency with the GI-ADR frequency of the widely used tumor necrosis factor-α inhibitor adalimumab (ADA). Methods. Reported GI-ADRs of ETN for rheumatic diseases were collected from the Dutch Biologic Monitor and DREAM registries. We described the clinical course of GI-ADRs and compared the frequency with ADA in both data sources using Fisher exact test. Results. Out of 416 patients using ETN for inflammatory rheumatic diseases in the Dutch Biologic Monitor, 25 (6%) patients reported 36 GI-ADRs. In the DREAM registries 11 GI-ADRs were registered for 9 patients (2.3%), out of 399 patients using ETN, with an incidence of 7.1 per 1000 patient-years. Most GI-ADRs consisted of diarrhea, nausea, and abdominal pain. GI-ADRs led to ETN discontinuation in 1 patient (4%) and dose adjustment in 4 (16%) in the Dutch Biologic Monitor. Eight GI-ADRs (73%) led to ETN discontinuation in the DREAM registries. The frequency of GI-ADRs of ETN did not significantly differ from GI-ADRs of ADA in both data sources (Dutch Biologic Monitor: ETN 8.7% vs ADA 5.3%, P = 0.07; DREAM: ETN 2.8% vs ADA 4.7%, P = 0.16). Conclusion. Most GI-ADRs associated with ETN concerned gastrointestinal symptoms. These ADRs may lead to dose adjustment or ETN discontinuation. The frequency of ETN-associated GI-ADRs was comparable to the frequency of ADA-associated GI-ADRs. Knowledge about these previously unknown ADRs can facilitate early recognition and improve patient communication

Uncovering the heterogeneity of disease impact in axial spondyloarthritis:bivariate trajectories of disease activity and quality of life

Objective The goal of managing axial spondyloarthritis (axSpA) is to improve and maintain patients' health-related quality of life (HRQoL), mainly through targeting towards low disease activity. Here, we aim to gain insight into the joint evolution of HRQoL and disease activity by identifying and characterising latent subgroups of patients with longstanding disease displaying similar trajectories throughout 8 years of follow-up. Methods Data from Outcome in Ankylosing Spondylitis (AS) International Study (n=161) and Groningen Leeuwarden AS cohort (n=264) were used. Biennially, HRQoL was assessed by AS Quality of Life (ASQoL) and disease activity by AS Disease Activity Score-C reactive protein (ASDAS-CRP). Bivariate trajectories of these outcomes were estimated by group-based trajectory modelling. Next, trajectories were profiled by comparing the latent groups with respect to baseline factors using analysis of variance and chi(2) test. Results Five bivariate trajectories were distinguished, in which ASQoL and ASDAS-CRP were tightly linked: (t1) low impact of disease; (t2) moderate impact; (t3) high impact with major improvement; (t4) high impact with some improvement; (t5) very high impact. Profiling revealed, for example, that (t1) was characterised by male gender and Human Leucocyte Antigen B27 positivity; (t3) by younger age, shorter symptom duration and biological intake and (t5) by the highest proportion of females. Conclusions We identified five bivariate trajectories of HRQoL and disease activity demonstrating a clear mutual relationship. The profiles revealed that both individual-related and disease-related features define the type of disease course in respect to HRQoL and disease activity in axSpA. This may provide clinicians insight into the differences among patients and help in the management of the disease

Disseminating and assessing implementation of the EULAR recommendations for patient education in inflammatory arthritis:a mixed-methods study with patients' perspectives

OBJECTIVES: To explore patients' agreement and reasons for agreement or disagreement with the EULAR recommendations for patient education (PE) for people with inflammatory arthritis (IA). METHODS: This mixed-method survey collected data using snowball sampling. The survey had been translated into 20 languages by local healthcare professionals, researchers and patient research partners. It explored the degree to which patients with IA agreed with each recommendation for PE (0=do not agree at all and 10=agree completely) and their rationale for their agreement level in free text questions. Descriptive statistics summarised participants' demographics and agreement levels. Qualitative content analysis was used to analyse the free text data. Sixteen subcategories were developed, describing the reasons for agreement or disagreement with the recommendations, which constituted the categories. RESULTS: The sample comprised 2779 participants (79% female), with a mean (SD) age 55.1 (13.1) years and disease duration 17.1 (13.3) years. Participants strongly agreed with most recommendations (median 10 (IQR: 9-10) for most recommendations). Reasons for agreement with the recommendations included the benefit of using PE to facilitate collaborative care and shared decision making, the value of flexible and tailored PE, and the value of gaining support from other patients. Reasons for disagreement included lack of resources for PE, not wanting information to be tailored by healthcare professionals and a reluctance to use telephone-based PE. CONCLUSION: The EULAR recommendations for PE have been disseminated among patients with IA. Overall, agreement levels were very high, suggesting that they reflect patients' preferences for engaging in collaborative clinical care and using PE to facilitate and supplement their own understanding of IA. Reasons for not completely agreeing with the recommendations can inform implementation strategies and education of healthcare professionals

Minimal to no transfer of certolizumab pegol into breast milk: Results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Background Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. Methods CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. Results 19 CZP-Treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-Age infants. Conclusion When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-Â-free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. Trial registration number NCT02154425; Results

Assessing acceptability and identifying barriers and facilitators to implementation of the EULAR recommendations for patient education in inflammatory arthritis: a mixed-methods study with rheumatology professionals in 23 European and Asian countries

Objectives: To disseminate and assess the level of acceptability and applicability of the EULAR recommendations for patient education among rheumatology professionals across Europe and 3 Asian countries, and identify potential barriers and facilitators to their application.Methods: A parallel convergent mixed methods research design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0 to 10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes. Results: A total of 1159 participants completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were: lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were: tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment, and inviting patients to provide feedback on patient education delivery.Conclusions: This project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools

The Use of Mobile Health Apps in Clinical Practice Remains Challenging

According to several international recommendations, disease activity should be regularly monitored with validated outcome measures in patients with axial spondyloarthritis (axSpA), and therapy should be adapted accordingly.1-3 Increasingly, healthcare providers are encouraged to also use patient-reported outcomes (PROs) for this purpose, to capture valuable data from the patient's perspective