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Abstract Background The optimal retreatment strategy with rituximab for rheumatoid arthritis (RA) remains a point of discussion. Depending on local guidelines, rituximab can either be administered at fixed intervals or when losing disease control, balancing therapeutic effectiveness with drug overexposure. However, treatment based on loss of disease control may significantly affect patients’ lives, provoking uncertainty and potentially leading to progressive joint damage. Moreover, as low-dose rituximab proved to be effective in treating RA while decreasing toxicity, drug exposure may be limited by tapering down rituximab doses guided by disease activity. Methods RITUXERA is a 104-week open-label multicentre randomised controlled superiority trial. In total, 134 patients with RA treated with rituximab will be 1:1 randomised when in need of retreatment (DAS28-CRP ≥ 3.2 with previous rituximab administration at least 24 weeks earlier) to either a treat-to-target-driven fixed dose retreatment strategy (usual care group) or fixed interval disease-activity guided dose optimisation strategy (experimental group). The usual care group will be retreated with fixed rituximab doses (1 × 1000 mg IV) in case of loss of disease control (DAS28-CRP ≥ 3.2). The experimental group will receive a 24-weekly rituximab treatment while tapering down the dose in a decreasing sequence if DAS28-CRP ≤ 3.2: 1 × 1000 mg IV (maximal dose), 1 × 500 mg IV, and 1 × 200 mg IV (minimal dose). If DAS28-CRP exceeds 3.2 at the six-monthly retreatment, patients will receive and remain on the previous effective dose. Study visits are planned every 12 weeks. Primary outcome is the comparison of longitudinal patient-reported disease impact over 104 weeks, measured with the Rheumatoid Arthritis Impact of Disease (RAID) instrument, analysed using a linear mixed model. Main secondary outcome is the comparison of longitudinal disease activity (DAS28-CRP) over 104 weeks. Discussion The RITUXERA trial aims to explore the optimal retreatment strategy with rituximab for RA in terms of long-term patient-reported disease impact, by proposing a fixed interval disease activity-guided dose optimisation strategy as compared to a treat-to-target fixed dose strategy. Trial registration CTIS 2023–506638-59–01 (registration date: 07 September 2023), ClinicalTrials.gov NCT06003283 (registration date: 17 August 2023).

Objectives DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.Methods Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.Results 739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient’s decision or ‘sponsor request’). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.Conclusion Filgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

Objectives To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.Methods CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score – C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP

Abstract Background Rheumatoid arthritis (RA) considerably impacts patients’ lives. Patients’ confidence in their ability to manage this impact, or self-efficacy, can be supported with self-management interventions. One approach is to use mobile health (mHealth) applications, which can additionally provide insight into disease impact by remotely monitoring patient-reported outcomes. However, user engagement with mHealth-apps is variable, and concerns exist that remote monitoring might make patients overly attentive to symptoms. Methods App-based Education and GOal setting in RA (AEGORA) is a multicentre, pragmatic randomised controlled trial investigating an mHealth-based self-management intervention to improve self-efficacy and remotely monitor disease impact in patients with RA. The intervention is provided via an adapted version of the application Sidekick (Sidekick Health, Reykjavik, Iceland) and consists of education, goal setting, lifestyle advice, and remote assessment of the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire. Across two centres, 120 patients will be recruited and randomised (2:1:1) to usual care or intervention group A/B (study app with weekly/monthly prompts to complete the RAID, respectively). Outcomes are assessed at baseline and after 4–6 months. The primary endpoint is a clinically important improvement (≥ 5.5/110) in the Arthritis Self-Efficacy Scale in the combined intervention group compared to usual care. Secondary endpoints are (a) non-inferiority regarding pain catastrophising, as a measure of symptom hypervigilance; (b) superiority regarding the RAID, sleep quality, and physical activity; and (c) participant engagement with the study app. Finally, the relationship between engagement, prompted frequency of RAID questionnaires, and the primary and secondary outcomes will be explored. Discussion The AEGORA trial aims to study the effectiveness of mHealth-based, multicomponent self-management support to improve self-efficacy in the context of RA, while providing potentially valuable insights into temporal disease activity dynamics and the feasibility and possible negative effects of remote symptom monitoring in this population. Trial registration Clinicaltrials.gov NCT05888181. Retrospectively registered on March 23, 2023. Study inclusion started on March 3, 2023.

Objective This post hoc analysis of the FINCH 1–3 (NCT02889796, NCT02873936 and NCT02886728) studies assessed specific effects of filgotinib on pain control and their relationship with other aspects of efficacy in patients with rheumatoid arthritis (RA).Methods Assessments included: residual pain responses of ≤10 and ≤20 mm on a 100 mm visual analogue scale (VAS); the proportion of patients who achieved VAS pain responses in addition to remission or low disease activity by Disease Activity Score-28 with C-reactive protein (DAS28-CRP) or Clinical Disease Activity Index (CDAI) criteria.Results Across studies, filgotinib reduced pain from week 2, with responses sustained throughout the studies. In FINCH 1, at week 24, 35.8%, 25.0%, 24.6% and 11.6% of patients in the filgotinib 200 mg, filgotinib 100 mg, adalimumab and placebo arms (each plus methotrexate) achieved VAS pain ≤20 mm in addition to DAS28-CRP remission; 26.3%, 17.9%, 17.2% and 7.6% achieved VAS pain ≤10 mm in addition to DAS28-CRP remission. A similar pattern was seen for CDAI remission. Time during which VAS pain was ≤10 or ≤20 mm was longest with filgotinib 200 mg and comparable between adalimumab and filgotinib 100 mg. Similar findings were reported for filgotinib in FINCH 2 and 3.Conclusion In all RA populations studied, pain improvements occurred from week 2 and were sustained over time. In FINCH 1, filgotinib 100 mg provided similar pain amelioration to adalimumab, whereas filgotinib 200 mg resulted in greater pain improvement and higher proportion of patients with residual pain ≤10 or ≤20 mm and meeting DAS28-CRP remission criteria.

Background: Several retreatment strategies exist for rituximab in rheumatoid arthritis (RA). In some countries, reimbursement criteria require a loss of disease control for rituximab retreatment. Understanding the patients’ and rheumatologists’ perceptions regarding this retreatment strategy would be informative in identifying the optimal treatment administration schedule. Objectives: This study aimed to uncover patients’ and rheumatologists’ perceptions regarding retreatment strategies of rituximab. Design: Qualitative study – semi-structured interviews Methods: Patients with RA, treated with rituximab, and rheumatologists were invited to participate in a qualitative study consisting of individual, in-depth, semi-structured interviews. Interviews were analysed according to the Qualitative Analysis Guide of Leuven. Results: A total of 16 patients and 13 rheumatologists were interviewed. Benefits (e.g. decreased risk of overtreatment, cost savings and long-lasting effectiveness of rituximab) and barriers (e.g. fluctuating disease activity, slow mode of action and increased glucocorticoid use) of on-flare retreatment were identified. To effectively treat on-flare, flares must first be identified timely. Both stakeholder groups acknowledged that patients are capable of recognizing flares. However, the patient’s ability to discriminate between inflammatory and other types of pain was perceived as difficult. Furthermore, patients and rheumatologists stressed that patients must timely seek professional help in case of a flare, followed by a swift response from the rheumatologists. Remarkably, retreatment was approached in various ways among rheumatologists, and not always adhering strictly to the on-flare reimbursement criteria. Conclusion: This study revealed that both stakeholder groups perceived the heterogeneity in recognition of and reaction to a flare as important in influencing the effectiveness of the on-flare retreatment strategy. Moreover, this study identified the benefits and barriers of treating on-flare, which could be informative for daily practice decisions.

Objectives Although eHealth tools are potentially useful for remote disease monitoring, barriers include concerns of low engagement and high attrition. We aimed to summarise evidence on patients’ engagement and attrition with eHealth tools for remotely monitoring disease activity/impact in chronic arthritis.Methods A systematic literature search was conducted for original articles and abstracts published before September 2022. Eligible studies reported quantitative measures of patients’ engagement with eHealth instruments used for remote monitoring in chronic arthritis. Engagement rates were pooled using random effects meta-analysis.Results Of 8246 references, 45 studies were included: 23 using smartphone applications, 13 evaluating wearable activity trackers, 7 using personal digital assistants, 6 including web-based platforms and 2 using short message service. Wearable-based studies mostly reported engagement as the proportion of days the tracker was worn (70% pooled across 6 studies). For other eHealth tools, engagement was mostly reported as completion rates for remote patient-reported outcomes (PROs). The pooled completion rate was 80%, although between-study heterogeneity was high (I2 93%) with significant differences between eHealth tools and frequency of PRO-collection. Engagement significantly decreased with longer study duration, but attrition varied across studies (0%–89%). Several predictors of higher engagement were reported. Data on the influence of PRO-reporting frequency were conflicting.Conclusion Generally high patient engagement was reported with eHealth tools for remote monitoring in chronic arthritis. However, we found considerable between-study heterogeneity and a relative lack of real-world data. Future studies should use standardised measures of engagement, preferably assessed in a daily practice setting.Trial registeration number The protocol was registered on PROSPERO (CRD42021267936).

Abstract Background Shifts in treatment strategies for rheumatoid arthritis (RA) have made ambulatory care more labour-intensive. These developments have prompted innovative care models, including mobile health (mHealth) applications. This study aimed to explore the perceptions of mHealth-inexperienced stakeholders concerning these applications in RA care. Methods We performed a qualitative study by focus group interviews of stakeholders including RA patients, nurses specialised in RA care and rheumatologists. The qualitative analysis guide of Leuven (QUAGOL), which is based on grounded theory principles, was used to thematically analyse the data. In addition, the Persuasive Systems Design (PSD) model was used to structure recommended app-features. Results In total, 2 focus groups with nurses (total n = 16), 2 with patients (n = 17) and 2 with rheumatologists (n = 25) took place. Six overarching themes emerged from the analysis. Efficiency of care and enabling patient empowerment were the two themes considered as expected benefits of mHealth-use in practice by the stakeholders. In contrast, 4 themes emerged as possible barriers of mHealth-use: the burden of chronic app-use, motivational aspects, target group aspects, and legal and organisational requirements. Additionally, recommendations for an ideal mHealth-app could be structured into 4 domains (Primary Task Support, Dialogue Support, Social Support and System Credibility) according to the PSD-framework. Most recommended features were related to improving ease of use (Task Support) and System Credibility. Conclusions Although mHealth-apps were expected to improve care efficiency and stimulate patient empowerment, stakeholders were concerned that mHealth-app use could reinforce negative illness behaviour. For mHealth-apps to be successful in practice, challenges according to stakeholders were avoiding long-term poor compliance, finding the target audience and tailoring a legal and organisational framework. Finally, the ideal mHealth-application should above all be trustworthy and easy to use.

Objective This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).Methods This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population.Results Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP)

Objectives To explore treatment outcomes preferred by patients with early rheumatoid arthritis (RA) and how these change throughout the early disease stage across three European countries.Methods A longitudinal, qualitative, multicentre study was conducted in Belgium, the Netherlands and Sweden. 80 patients with early RA were individually interviewed 3–9 months after treatment initiation and 51 of them participated again in either a focus group or an individual interview 12–21 months after treatment initiation. Data were first analysed by country, following the Qualitative Analysis Guide of Leuven (QUAGOL). Thereafter, a meta-synthesis, inspired by the principles of meta-ethnography and the QUAGOL, was performed, involving the local research teams.Results The meta-synthesis revealed 11 subthemes from which four main themes were identified: disease control, physical performance, self-accomplishment and well-being. ‘A normal life despite RA’ was an overarching patient-preferred outcome across countries. Belgian, Dutch and Swedish patients showed many similarities in terms of which outcomes they preferred throughout the early stage of RA. Some outcome preferences (eg, relief of fatigue and no side effects) developed differently over time across countries.Conclusions This study on patient-preferred outcomes in early RA revealed that patients essentially want to live a normal life despite RA. Our findings help to understand what really matters to patients and provide specific insights into the early stage of RA, which should be addressed by clinicians of different disciplines from the start of treatment onwards.

Abstract Background There is a remarkable lack of detailed knowledge on pain areas in axial spondyloarthritis (axSpA), and their clinical relevance is largely unknown. Pain area may reflect local disease processes, but amplification of nervous system signalling may alter this relationship. Also, gender differences in pain area may exist in axSpA, possibly confounding disease activity outcomes. Therefore, we firstly detailed pain locations in axSpA and evaluated gender differences. Secondly, we explored the relationship of regional pain definitions with clinical outcomes. Finally, we explored the role of pain area in the assessment of disease activity. Methods Body charts informed on the presence of axial, peripheral articular and non-articular pain in 170 patients (108 men, 62 women) with axSpA. Multivariate Odds Ratios (ORs) were used to compare genders. General linear models were used to explore clinical differences in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), activity limitations (Bath Ankylosing Spondylitis Functional Index [BASFI]), fear of movement (Tampa Scale for Kinesiophobia 11-item version [TSK-11]), anxiety (Hospital Anxiety and Depression Scale subscale anxiety [HADS-A]) and depression (HADS subscale depression [HADS-D]) between four subgroups classified by widespread non-articular pain (WNAP+/−) and physician global assessment of disease activity (PGDA+/−) (p

An amendment to this paper has been published and can be accessed via the original article.

Objectives To identify and characterise a subgroup of patients with early rheumatoid arthritis (RA) reporting not feeling well 1 year after treatment initiation despite achieving optimal disease control according to current treatment standards.Methods This observational study included participants of the Care in early RA trial with a rapid and sustained response (DAS28CRP

Biological treatment of rheumatoid arthritis (RA) is one of the cornerstones of current treatment strategies for the disease. Surprisingly little information exists on whether the route of administration affects patients' treatment satisfaction. It is equally unclear whether rheumatologists are able to accurately perceive their patients' appreciation. Thus, the Belgian Be-raise survey aimed to examine whether RA patient's experience of their current biological treatment coincided with the treating physician's perception.A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists providing data obtained from 550 RA patients. Patients under stable dose of biologics for at least 6 months, were enrolled consecutively and all completed questionnaires. Separate questionnaires were completed by the treating rheumatologist which evaluated their patient's perception of the route of treatment administration. This study therefore evaluates whether a treating physician perceives the satisfaction with the route of administration to the same degree as the patient.Completed questionnaires were obtained from 293 and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous (SC) route of administration, respectively. 58.4% of patients were in DAS28-CRP(3) remission. Patient satisfaction with disease control was higher (44% scored ≥ 9) than that of the treating physician (35%), regardless of the route of administration (p< 0.01). No differences were seen for the patients treated with an IV as opposed to a SC route of administration. The physician´s perception of patient's satisfaction with disease control was markedly lower for IV treated patients as opposed to SC treated patients (p< 0.001).Patients' satisfaction with biological treatment is high, but there is a considerable mismatch between patients´ and rheumatologists´ appreciation on the route of administration of biological therapy in RA. Physicians consistently consider IV biological therapy to be less satisfactory. Patient´s appreciation is largely dependent on disease control, irrespective of the route of administration. Therefore, and encouraging shared decision making, we suggest that physicians and patients discuss the route of administration of biologicals in an open way.

In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p

Abstract Background Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. Methods A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. Results Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7–12.9) in EM patients and 20.9% (95% CI 6.8–64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98–12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. Conclusions In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.

Abstract Background Rheumatoid arthritis (RA) is a heterogeneous disease with established poor prognostic factors such as seropositivity, joint damage, and high disease activity at an early, treatment-naïve stage of disease. However, few studies have examined if specific joint locations are correlated with these factors in such a population. This analysis explored the potential correlation of individual swollen and erosive joints with other disease characteristics at baseline and with remission rates in a post-hoc analysis of the Phase III randomized AGREE study. Methods Methotrexate (MTX)-naïve, erosive, RF- and/or ACPA-positive early RA patients (N = 509) were retrospectively evaluated. Baseline joint swelling was analyzed for large and small joints. Baseline erosions were analyzed for wrist, MCP1–5, IP1, PIP2–5 and MTP1–5. Remission rates were assessed after 6 months of treatment with abatacept (ABA) + MTX (N = 256) or MTX (N = 253). The following statistical tests were used: Chi-Square or Fisher’s exact test (categorical variables); Student’s t-test or Wilcoxon rank-sum test (continuous variables); continuity-corrected Chi-square test (efficacy remission endpoints). Results Baseline swelling was most frequent in wrist (91.9%) and MCP2 joint (89.1%), while baseline erosion was most frequent in MTP5 joint (43.5%). Swollen shoulder was significantly correlated (p

Anti-tumour necrosis factors (anti-TNFs) are established as first-line biological therapy for rheumatoid arthritis (RA) with over two decades of accumulated clinical experience. Anti-TNFs have well established efficacy/safety profiles along with additional benefits on various comorbidities. However, up to 40% of patients may respond inadequately to an initial anti-TNF treatment because of primary non-response, loss of response, or intolerance. Following inadequate response (IR) to anti-TNF treatment, clinicians can consider switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action, such as Janus kinase inhibitors, interleukin-6 receptor blockers, B-cell depletion agents, and co-stimulation inhibitors (swapping). While European League Against Rheumatism recommendations for pharmacotherapeutic management of RA, published in 2020, are widely regarded as helpful guides to clinical practice, they do not provide any clear recommendations on therapeutic choices following an IR to first-line anti-TNF. This suggests that both cycling and swapping treatment strategies are of equal value, but that the treating physician must take the patient’s individual characteristics into account. This article considers which patient characteristics influence clinical decision-making processes, including the reason for treatment failure, previous therapies, comorbidities, extra-articular manifestations, pregnancy, patient preference and cost-effectiveness, and what evidence is available to support decisions made by the physician.

Abstract Background Rheumatoid arthritis (RA) is associated with a 5 to 10 years reduction in life expectancy due to premature atherosclerosis. This reduction is the consequence of traditional cardiovascular risk factors (TCRF) as well as systemic inflammation. The aim of the present study was to describe the prevalence and factors associated with subclinical atherosclerosis in RA at the University Hospital of Kinshasa (UHK). Methods Patients with a diagnosis of RA based on the 2010 ACR/EULAR criteria were included in this cross-sectional study from 1 June 2014 to 31 May 2015 at the UHK. RA disease activity was measured using the DAS28-ESR. Active RA was defined by a DAS 28 > 2.6. Severe RA was defined by the presence of extra-articular manifestation, joint erosions on X-rays or HAQ ≥0.5. An assessment of subclinical atherosclerosis was performed by the measurement of the carotid intima-media thickness (cIMT) using two-dimensional ultrasonography. Subclinical atherosclerosis was defined by a cIMT ≥0.9 mm. A diagnosis of atheroma plaque was retained when the cIMT was ≥1.5 mm. The association between subclinical atherosclerosis and potential risk factors was modeled using logistic regression analysis. Results We recruited 75 patients. The average age was 51.8 ± 14.6 years, with a sex ratio F/M of 4. The prevalence of subclinical atherosclerosis was 32%. In logistic regression being a woman of ≥55 years old (aOR 10.6, 95% CI [2.087–53.82], p = 0.028), DAS28-ESR > 2.6 (aOR 3.5,95% CI [1.55–10.38], p = 0.044), severe RA (aOR 32.6,95% CI [1.761–60.37],p = 0.035), high blood pressure (aOR 22.4,95% CI [5.04–99.41], p = 0.005) and obesity (aOR 32.3, 95% CI [2.606–40.73], p = 0.026) emerged as factors associated with subclinical atherosclerosis. Conclusion Subclinical atherosclerosis is common in RA patients attending the UHK. It appears to be associated with RA disease activity and severity apart from traditional cardiovascular risk factors. These results suggest that early management of subclinical atherosclerosis targeting remaining RA disease activity and cardiovascular risk factors could slow down progression to clinical cardiovascular disease.

The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as “biobetters” or “value-added medicines,” are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.

Abstract Background The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies. Methods Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. PROs were measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the Patient Global Assessment of Disease Activity (Patient Global), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the 36-Item Short Form Health Survey (SF-36). Results At week 12, improvements in all PROs, apart from the SF-36 mental component in the add-on study, were statistically better with filgotinib than placebo; some improvements were noted as early as the first assessment time point (week 1 or week 4). Filgotinib improved HAQ-DI by 0.58–0.84 points, FACIT-Fatigue by 6.9–11.4 points, Patient Global by 25.2–35.6 mm, and Pain by 24.2–37.9 mm; scores were maintained or improved to week 24. Across all PROs, more patients achieved minimal clinically important differences and normative values with filgotinib 200 mg than placebo. Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in PROs between weeks 12 to 24. Conclusions Filgotinib as MTX add-on therapy or as monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health-related quality of life and functional status in patients with active RA. Trial registration MTX add-on study: ClinicalTrials.gov, NCT01888874. Registered on 28 June 2013. Monotherapy study: ClinicalTrials.gov, NCT01894516. Registered on 10 July 2013.

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.

IntroductionTraditionally, assessment in axial Spondyloarthritis (aSpA) includes the evaluation of the capacity to execute tasks, conceptualized as physical function. The role of physical activity, defined as movement-related energy expenditure, is largely unknown and almost exclusively studied using patient-reported outcome measures. The aims of this observational cross-sectional study are to compare physical activity between patients with aSpA and healthy controls (HC) and to evaluate the contribution of disease activity to physical activity differences between groups.MethodsForty patients with aSpA were matched by age, gender, period of data acquisition in terms of days and season to 40 HC. Physical activity was measured during five consecutive days (three weekdays and two weekend days) using ambulatory monitoring (SenseWear Armband). Self-reported disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Differences in physical activity between patients with aSpA and HC were examined with Wilcoxon signed-rank tests and a mixed linear model. Difference scores between patients and HC were correlated with disease activity.ResultsAverage weekly physical activity level (Med(IQR); HC:1.54(1.41-1.73); aSpA:1.45(1.31-1.67),MET) and energy expenditure (HC:36.40(33.43-41.01); aSpA:34.55(31.08-39.41),MET.hrs/day) were significantly lower in patients with aSpA. Analyses across intensity levels revealed no significant differences between groups for inactivity and time spent at light or moderate physical activities. In contrast, weekly averages of vigorous (HC:4.02(1.20-12.60); aSpA:0.00(0.00-1.20),min/d), very vigorous physical activities (HC0.00(0.00-1.08); aSpA:0.00(0.00-0.00),mind/d) and moderate/(very)vigorous combined (HC2.41(1.62-3.48); aSpA:1.63(1.20-2.82),hrs/d) were significantly lower in patients with aSpA. Disease activity did not interact with differences in physical activity between patients with aSpA and HC, evidenced by non-significant and very low correlations (range: -0.06-0.17) between BASDAI and HC-aSpA patients' difference scores.ConclusionsPatients with aSpA exhibit lower physical activity compared to HC and these differences are independent of self-reported disease activity. Further research on PA in patients with aSpA should be prioritized.

The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

Objectives. To assess discrepancies between perception of Belgian rheumatologists on eligibility of RA patients for anti-TNF treatment and Belgian reimbursement criteria and to compare Belgian with Dutch criteria and UK guidelines. Methods. Consecutive MTX-experienced patients with active RA were recruited from 25 private and academic rheumatology practices. Discrepancies between eligibility for anti-TNF treatment according to the rheumatologist and fulfillment of Belgian reimbursement criteria [HAQ 25%, tender joint count (TJC) and swollen joint count (SJC) 8; 1 erosion; failure of 2 DMARDs including MTX; no tuberculosis] were recorded. Reasons for failing the Belgian criteria and results of applying Dutch reimbursement criteria and UK guidelines on the dataset were analysed. Results. Of 492 patients, rheumatologists considered 135 (27.4%) as eligible, whereas Belgian criteria were fulfilled for only 34 (6.9%). Positive predictive value (PPV) of rheumatologists’ perception on eligibility for fulfillment of Belgian criteria was 22.9%, whereas negative predictive value (NPV) was 99.1%. The 104 patients (21.1%) considered eligible despite criteria not being fulfilled had significantly greater TJCs, SJCs, disease activity score (DAS28) and Rheumatoid Arthritis Disease Activity Index scores than the 385 patients (78.2%) in the no-discrepancy group. Number of swollen joints, HAQ and erosions mainly accounted for discrepancies. Of 492 patients, 263 (53.4%) qualified for Dutch criteria and 41 (8.3%) for UK guidelines. PPV of Belgian rheumatologists’ perception was 72.6% for fulfilling Dutch criteria (NPV 49.6%) and 23.4% for UK guidelines (NPV 96.7%). Conclusions. Rheumatologists consider more RA patients eligible for anti-TNF treatment than would be reimbursed according to Belgian criteria. Dutch guidelines, based on DAS28, match more closely eligibility according to Belgian rheumatologists. [ABSTRACT FROM AUTHOR]

We report a case of a woman with secondary oxalosis after jejunoileal bypass surgery for obesity, who presented with oxalate stone disease and renal insufficiency requiring dialysis. Thirty years after surgery, longstanding osteoarticular symptoms were recognized as oxalate arthritis. Eventually, she also developed oxalate vasculitis, which improved with corticoid treatment and intensification of dialysis. Work-up for kidney transplantation revealed AA amyloidosis on gastric and colonic biopsies. Since no other cause of chronic inflammation could be identified, it was concluded that the amyloidosis was secondary to oxalate arthritis and vasculitis. To our knowledge, this is the first report on this association. [ABSTRACT FROM AUTHOR]