Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial.

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 <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups. RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%). CONCLUSION: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104. TRIAL REGISTRATION NUMBER: NCT03649061. CTR PILOT APPROVAL BELGIUM: S59474, EudraCT number: 2017-004054-41.

Effects of implementing a vaccination tool in the electronic medical record on vaccination coverage of patients with immune-mediated inflammatory diseases: a prospective cohort study.

BACKGROUND: The rising incidence of immune-mediated inflammatory diseases (IMID) requires innovative management strategies, including effective vaccination. We aimed to assess the impact of an electronic medical record (EMR)-integrated vaccination tool on vaccination coverage among patients with inflammatory bowel diseases (IBD), rheumatological and dermatological conditions. METHODS: A prospective observational study compared vaccination coverage before (2018) and after (2021) implementing the module. Vaccination data for influenza, pneumococcus, hepatitis B and tetanus, and potential predictors were collected from 1430 IMID patients (44.9% male, median age (interquartile range [IQR]) 54 (40-66) years, 789 with IBD, 604 with rheumatological and 37 with dermatological conditions). Data were analysed using McNemar, chi-square tests and multinominal logistic regression. RESULTS: Significant increases in pneumococcus (56.6% to 73.1%, p < .001) and hepatitis B vaccination (62.2% to 75.9%, p < .001) were observed. Influenza vaccination rates increased among IBD (76.2% to 80.5%, p = .006) but remained stable overall (73.1% to 73.2%, p = 1.000). Tetanus vaccination rates decreased (71.5% to 55.0%, p < .001). The proportion of fully vaccinated patients (against influenza in the past year for patients >50 years old and/or under immunosuppressive therapy, against pneumococcus in the past 5 years for patients >65 years old and/or under immunosuppressive therapy and additionally against hepatitis B for IBD patients) rose from 41.3% to 54.8% (p < .001 all using McNemar). Factors associated with vaccinations included age, immunosuppressive therapy and education level. CONCLUSIONS: Increased vaccination coverage was measured after implementing the vaccination tool. The COVID19 pandemic and the 2018 measurement might have increased vaccination awareness. Education of patients and healthcare professionals remains crucial.

Patients' and rheumatologists' perceptions on dose reduction of rituximab in rheumatoid arthritis.

OBJECTIVE: The recommended dose of a rituximab course for the treatment of Rheumatoid Arthritis (RA) consists of two infusions of 1000 mg with a 2-week interval. Evidence is growing that a lower dose could be as effective. We aimed to investigate patients' and rheumatologists' perceptions on dose reduction of rituximab. METHODS: Patients with RA treated with rituximab, and rheumatologists were invited for a qualitative study via individual semi-structured interviews. Participants were recruited based on purposive sampling to ensure diversity. Interviews were analysed according to the principles of grounded theory and the constant comparative method. RESULTS: Sixteen patients and 13 rheumatologists were interviewed. Patients and rheumatologists perceived the benefits of rituximab dose reduction for reasons of safety and societal costs. Furthermore, available evidence for the effectiveness of lower doses was mentioned as an argument in favour, in addition to the possibility to tailor the dose based on the patients' clinical manifestations. However, patients and rheumatologists had concerns about the potential loss of effectiveness and quality of life. Moreover, some rheumatologists felt uncomfortable with dose reduction due to insufficient experience with rituximab in general. Patients and rheumatologists emphasised the importance of shared decision-making, underscoring the pivotal role of physicians in this process by explaining the reasoning behind dose reduction. CONCLUSION: Although some concerns on effectiveness were perceived, both patients and rheumatologists saw potential benefits of dose reduction in terms of safety, societal costs, and application of a personalised approach. As a result, most rheumatologists and patients showed a willingness to consider dose reduction strategies.

Definitions of rheumatoid arthritis flare and how they relate to patients' perspectives: A scoping review of qualitative and quantitative evidence.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by intermittent flares of disease activity with a significant impact on patients' lives. However, distinguishing flare from daily symptom variation may be approached differently by patients and healthcare providers, potentially hampering shared decision-making when treating RA. OBJECTIVES: To provide a comprehensive overview of RA flare definitions reported in the published literature, and to compare these with patients' perceptions of the flare concept according to qualitative evidence. METHODS: A systematic search was conducted on August 30th, 2022, and updated on September 30th, 2023, for both quantitative and qualitative studies reporting "flare" or related terms in the context of RA. We searched the following databases: Pubmed, EMBASE, Web of Science, Cochrane Library, and CINAHL. Definitions of RA flare reported in quantitative studies were summarized descriptively. In parallel, a thematic synthesis of qualitative studies was performed to outline patients' views on the concept of flare, and to compare these with the currently used definitions. RESULTS: Among 32,864 potentially eligible records, 304 studies were included, 5 of which used qualitative/mixed methods to study patients' perceptions of flare. Remarkably, 62 different definitions for RA flare were reported, with many studies reporting more than one. The most commonly used definitions (54 %) were based on disease activity indices, with DAS28-based definitions the most widely applied (84 %). For each of the disease activity indices, several different cutoffs to define flares were used. Various definitions based on physician report were applied in 24 % of cases, while patient-reported criteria represented only 15 % of the applied definitions. Thematic synthesis of the qualitative/mixed-methods studies highlighted the multidimensional impact of flares on patients' lives, resulting in five sequential overarching themes: "Living with RA: a balancing act", "Flare: a disturbance of this balance", "The biopsychosocial impact of flares", "Self-management: the first line of defense", and "Medical help: the last resort". In turn, these five themes were underpinned by a central theme of "Uncertainty and variability". CONCLUSION: We found a striking heterogeneity regarding the conceptualization and measurement of RA flare in the published literature. Although qualitative evidence highlighted the considerable impact of flares on patients' wellbeing, the majority of reported flare definitions were not based on patient report. There is a need to bridge this gap by aligning patients' and healthcare professionals' views on what distinguishes a flare from acceptable symptom variability when living with RA.

To flare or not to flare: patients' and rheumatologists' perceptions on the on-flare retreatment strategy of rituximab in rheumatoid arthritis.

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.

Patient-physician discordance impairs outcomes in early rheumatoid arthritis through less consistent treat-to-target implementation.

OBJECTIVES: We aimed to assess whether patient-physician discordance regarding disease activity affects T2T-implementation and clinical outcomes in rheumatoid arthritis (RA). METHODS: This was an analysis of the 2-year T2T-guided trial Care in early RA (CareRA). During year 1, DMARD escalations were mandated by the protocol when DAS28-CRP was >3.2. During year 2, treatment was at the rheumatologists' discretion. At each visit we assessed T2T-implementation, defined as escalating DMARDs if DAS28-CRP >3.2. Patient-physician discordance was defined by the discordance score (DS), a weighted difference between patient-reported and clinical/laboratory outcomes. Using generalised linear mixed models and multilevel mediation analysis, we studied the association between time-varying DS, T2T-implementation and the odds of remission (SDAI ≤3.3), physical functioning (HAQ-score), and radiographic progression at year 2. RESULTS: Over 2 years, 379 patients were assessed at 3129 follow-up visits. On 445 (14%) of these visits, DAS28-CRP was >3.2, and DMARDs were escalated in 217/445 (49%) of such cases. T2T-implementation declined over time and was consistently lower during the second year (year 1: 57-66%; year 2: 17-52%). Higher DS over time was negatively associated with remission and physical functioning at year 2, partly mediated by a lower proportion of T2T-adherent visits. No such association was found for radiographic progression. CONCLUSION: Even in a trial setting, T2T was applied on only around 50% of visits. T2T was less likely to be implemented with increasing patient-physician discordance regarding disease activity, which was in turn associated with less remission and worse functional outcome, but not with radiographic progression.