OBJECTIVES:To assess the prevalence of anti-aminoacyl tRNA synthetase antibodies (anti-ARS) in a large cohort of untreated early rheumatoid arthritis (RA) patients compared to healthy controls. METHODS:The baseline serum samples of patients with early RA (n = 332) included in the multicentre CareRA trial, a completed interventional trial in untreated early RA, and healthy controls (n = 72) were screened for anti-ARS antibodies with a commercial dot immunoassay (DIA). Radiolabelled protein immunoprecipitation (IP) was performed to confirm the presence of suspected anti-ARS antibodies, in addition to HEp-2 indirect immunofluorescence and a commercial line immunoassay (LIA). RESULTS:Anti-ARS antibodies (anti-PL12 n = 2, anti-OJ n = 1) were detected in 0.9% of early RA patients using a DIA, of which one anti-PL12-positive sample was also positive on LIA. Presence of these anti-ARS antibodies could, however, not be confirmed by protein immunoprecipitation. No anti-ARS antibodies were detected in the healthy control group. CONCLUSION:We report that the presence of anti-ARS antibodies cannot be confirmed by IP in a multicentre cohort of untreated early RA patients. Anti-ARS autoantibodies should not routinely be evaluated in patients with early RA. Sensitivity and specificity issues with DIA and LIA for anti-ARS should be considered in the interpretation of anti-ARS testing.

OBJECTIVE:This study aims to evaluate whether the 10-item Patient-Reported Outcomes Measurement Information System Scale v1.2-Global Health (PROMIS-GH) is useful to assess global mental health (GMH) and global physical health (GPH) in individuals with musculoskeletal disorders. METHODS:PROMIS-GH was administered to 4,295 individuals (mean ± SD age 56 ± 14 years, 70% female, chronic musculoskeletal pain [n = 1,142], rheumatoid arthritis [n = 1,987], hip/knee osteoarthritis [n = 418], and undergoing physiotherapy [n = 947]). We investigated the legitimacy of calculating a GMH and a GPH subscale score (confirmatory factor analyses) and of converting raw ordinal subscale scores to interval scores (checking item response theory [IRT] assumptions [unidimensionality, local independence, and monotonicity] and graded response model fit), the ability of the subscales to discriminate different levels of health (items' discrimination parameters α) to cover the relevant range of GMH and GPH (range of difficulty parameters β) and their precision (item- and subscale-level information), and to compare demographic and clinical subgroups (differential item functioning [DIF]). RESULTS:It is legitimate to calculate a GMH and a GPH subscale score (comparative fit index = 0.98/0.97, Tucker-Lewis index = 0.97/0.95, root mean square error of approximation = 0.15/0.19, and standardized root mean square residual = 0.05/0.07) and to convert raw scores to interval scores (IRT assumptions met and adequate model fit). Discrimination (items' α ≥ 2), coverage (lowest β ≤ -2) and precision (reliability ≥ 0.70 for large portions of the health domain) were adequate for all items, except item Global10, underscoring that they can distinguish individuals with different levels of GMH and GPH with precision. The subscales can be used to compare demographic and clinical subgroups (no DIF). CONCLUSION:PROMIS-GH can be used to measure GMH and GPH in individuals with musculoskeletal disorders. Replacement or improvement of the Global10 item could be considered.

Rituximab is known as an efficacious drug for the treatment of Rheumatoid Arthritis (RA). The original administration schedule consisted of two infusions of 1000 mg with a 2-week interval. We aimed to explore the long-term effectiveness of rituximab in daily clinical practice in patients with RA. Data of patients with RA treated with rituximab in a tertiary university hospital (2006–2019) were retrospectively collected from rituximab initiation until December 1st 2019 or rituximab discontinuation, whichever came first. Rituximab retreatment was based on a treat-to-target-approach guided by a 28-joint disease activity score (DAS28) ≥ 3.2, as dictated by national reimbursement criteria. Rituximab retention rate was investigated using a Kaplan-Meier survival curve. We collected data of 104 patients (59

OBJECTIVES:The aim of this work was to determine whether smartphone applications could support the self-management of RA and to investigate engagement and potential negative psychological effects with app-use. METHODS:App-based Education and GOal-setting in RA (AEGORA) was a multicentre randomized controlled trial with 2:1:1 allocation to usual care or two versions of an app-based self-management intervention for RA. The 16-week programme involved patient education, goal-setting and remote monitoring of the Rheumatoid Arthritis Impact of Disease (RAID) instrument, either weekly or monthly depending on randomization. The primary end point was improvement in the Arthritis Self-Efficacy Scale (ASES) after 16 weeks. Secondary endpoints included non-inferiority regarding the Pain Catastrophizing Scale (PCS) and superiority regarding patient-reported physical activity, sleep quality and RAID. App engagement and RAID scores were analysed descriptively. RESULTS:Overall, 122 patients were included: mean (s.d.) disease duration 12 (9) years, age 58 (11), 68% female, DAS28-CRP 2.4 (0.9). The intervention did not improve the ASES score over usual care (β 0.44, P = 0.87). Non-inferiority was established for the PCS (β -0.95 [95% CI -3.30, +1.40] favouring the intervention). Other predefined outcomes did not differ. App retention steadily declined to 43% by 16 weeks. Although the RAID remained stable over time overall, 35% of app users reported ≥1 episode of clinically relevant worsening over 16 weeks. CONCLUSION:This app-based self-management intervention was not superior to usual care regarding self-efficacy improvement. However, remote symptom monitoring provided valuable insight and did not increase pain catastrophizing, alleviating concerns regarding the psychological impact of remote monitoring with apps. TRIAL REGISTRATION NUMBER:clinicaltrials.gov, NCT05888181.

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.

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.

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.

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. 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. 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. CTIS 2023–506638-59–01 (registration date: 07 September 2023), ClinicalTrials.gov NCT06003283 (registration date: 17 August 2023).

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: We aimed to assess whether patient-physician discordance regarding disease activity affects treat-to-target (T2T) implementation and clinical outcomes in 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 generalized linear mixed models and multilevel mediation analysis, we studied the association between time-varying DS, T2T implementation and the odds of remission (Simplified Disease Activity Index <= 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.

ObjectiveTo discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.MethodsTwo RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies’ potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.ResultsWe identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.ConclusionWe identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.

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.

Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test–retest reliability were evaluated with Crohnbach’s alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12 months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test–retest reliability (Cronbach’s alpha 0.96; ICC 0.96 [95 https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE , EudraCT number 2012–004,631-22.

Background A treat-to-target (T2T) approach improves outcomes of rheumatoid arthritis (RA). However, T2T is applied in only two-thirds of real-world visits, while patient satisfaction, engagement and treatment success improve when patients and rheumatologists agree over T2T goals [1]. Consequently, discordance between patients' and rheumatologists' views on disease activity might hamper T2T implementation, impairing outcomes. Objectives To assess if patient-physician discordance in disease activity assessment affects the likelihood of T2T being applied, and how this influences remission. Methods This was a post-hoc analysis of the 2-year pragmatic randomized trial Care in early RA (CareRA), which compared several DMARD regimens with/without bridging glucocorticoids, in treatment-naïve patients with early RA. The trial was guided by T2T: during the first year, the protocol mandated specific DMARD adaptations in case of DAS28-CRP >3.2, with documentation of reasons for non-adherence. From week 52 onwards, treatment was at the rheumatologists' discretion.For each patient, we quantified T2T implementation as the proportion of study visits where DMARD treatment was adapted when DAS28-CRP was >3.2. Patient-physician discordance was defined by the discordance score (DS)[2], a weighted difference between patient-reported and clinical/laboratory outcomes, ranging from -1 to 1 with values >0 implying relatively more patient-perceived disease impact. First, we examined the longitudinal association between the DS and T2T implementation with a generalized linear mixed model (GLMM) adjusted for age, sex, autoantibodies, treatment, Rheumatic Disease Comorbidity Index and number of previous DMARDs. Additionally, we studied the association between time-varying DS, T2T implementation and the odds of remission (SDAI ≤3.3) at year 2, using a multilevel mediation model clustered within individual patients. All study visits until year 2 or drop-out were considered, with no imputation of missing treatment information. Other missingness was handled with multiple imputation. Results In all, 379 patients were included in CareRA, 322 of whom completed the trial. Over 2 years, 3129 follow-up visits with available treatment information took place. On 445 (14%) of these visits, DAS28-CRP was >3.2, and DMARD treatment was adapted in 217/445 (49%) of such cases. T2T use declined over time and was consistently lower during the second trial year, where treatment was no longer protocolized, with T2T implementation ranging from 52-66% in year 1 and from 17-38% in year 2.The mean DS was higher on visits where T2T was not applied (0.33 [SD 0.17]) than on T2T visits (0.18 [SD 0.17], p <0.001). In the GLMM, higher DS was associated with a lower probability of T2T being applied (OR 0.62 [95% CI 0.55-0.69] for 0.1 increase on DS, p <0.001). In multilevel mediation analysis, higher DS over time was associated with decreased odds of remission at year 2, and this effect was partly mediated by lower T2T implementation (Figure 1). Conclusion Patient-physician discordance in disease activity assessment was associated with a decreased probability of achieving remission. This association was partly explained by rheumatologists appearing less likely to apply a T2T strategy when their assessment of disease activity differed from the patient's. These findings highlight the importance of an open dialogue between physicians and patients about their evaluation of disease activity before applying this as a target for treatment modification. References [1]Taylor et al. RMD Open, 2022, 8:e002658.[2]Pazmino et al. Rheumatology (Oxford), 2022, 62(1):108-115. Acknowledgements MD has received a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek (FWO) (grant number 1S85521N). CareRA was supported by a grant from the Flemish Government Agency for Innovation by Science and Technology (IWT) and by grants from the Fund for Scientific Research in Rheumatology (FWRO) and the Academic Foundation of Leuven. Disclosure of Interests None Declared.Figure 1Mediation analysis of the association between discordance score over time, T2T implementation and the probability of remission at year 2.Reported are the standardized regression coefficients with indicators of significance (*** p < 0.001).T2T = treat-to-target, SDAI = Simple Disease Activity Index

OBJECTIVE:Fatigue is common in rheumatoid arthritis (RA). We aimed to explore its longitudinal course, predictors and association with disease activity in early RA. METHODS:Data came from the 2-year treat-to-target trial CareRA (Care in early RA) and its 3-year extension. Fatigue was measured on Visual Analogue Scale, Multidimensional Fatigue Inventory and Short Form-36 (SF-36) vitality. Longitudinal fatigue trajectories were identified with multivariate growth mixture modelling. Early predictors of fatigue and the association of fatigue and its trajectories with disease activity and clinical/psychosocial outcomes were studied with linear mixed models and multilevel mediation. RESULTS:We included 356 and 244 patients in the 2-year and 5-year analyses, respectively. Four fatigue trajectories were identified: rapid, gradual, transient improvement and early deterioration, including 10%, 14%, 56% and 20% of patients. Worse pain, mental health and emotional functioning were seen in the early deterioration group. Higher pain, patient global assessment (PGA) and disability (Health Assessment Questionnaire), lower SF-36 mental components, and fewer swollen joints at baseline predicted higher fatigue over 5 years, while early disease remission strongly improved 5-year fatigue. The association between Simple Disease Activity Index and fatigue was mediated by PGA, pain, mental health and sleep quality. CONCLUSIONS:Although fatigue evolves dynamically over time in early RA, most patients do not achieve sustained fatigue improvement despite intensive disease-modifying antirheumatic drug therapy. Higher 5-year fatigue levels were seen in patients with more perceived disease impact and fewer swollen joints at baseline. Conversely, early inflammatory disease control strongly improved long-term fatigue, pointing towards an early window of opportunity to prevent persistent fatigue.

Objective To unravel disease impact in early RA by separately quantifying patient-reported (PRF), clinical (CF) and laboratory (LF) factors. We propose a new indicator, the discordance score (DS), for early identification and prediction of patient's unmet needs and of future achievement of sustained remission (SR) and RA-related quality of life (QoL). Methods Factor-scores obtained by factor analysis in the CareRA trial, allowed to compute DS, reflecting the difference between PRF and the mean of CF and LF. Improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time points per factor-score were calculated and compared between patients achieving/not achieving sustained (week 16-104) remission (DAS28CRP < 2.6) with ANOVA. Logistic and linear regressions were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16. Results PRF, CF and LF scores improved rapidly within 8 weeks. PRF improved 57%, CF 90% and LF 27%, in those achieving SR, compared with 32% (PRF: P = 0.13), 77% (CF: P < 0.001) and 9% (LF: P = 0.36) in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF, respectively, compared with 33.2, 10.1 and 7.2 in participants not achieving SR (P < 0.001 for all). Early discordance was associated with later factor scores, QoL and self-efficacy. Conclusions All factor scores improved rapidly, especially in patients achieving sustained remission. Patient-reported burden improved less. Discordance scores could help predicting the need for additional non-pharmacological interventions to achieve sustained remission and decrease disease impact.

ObjectiveThis study investigated how psychosocial aspects of disease affect the probability of achieving sustained remission in early rheumatoid arthritis (RA) and explored the directionality of this relationship.MethodsData were analyzed from the randomized controlled Care in Early RA trial. Sustained remission was defined as a continued Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) of <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF‐36) health survey, Revised Illness Perception Questionnaire (IPQ‐R), and the Utrecht Coping List. These psychosocial variables were studied at baseline and at week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox proportional hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28‐CRP was explored with cross‐lagged panel models (CLPMs).ResultsSustained DAS28‐CRP remission was associated with higher SF‐36 scores and less passive coping at baseline and with higher SF‐36 scores and more positive IPQ‐R outcomes at week 16. Among patients in DAS28‐CRP remission at week 16 (n = 287), 2 subgroups were identified: a low psychosocial burden group (n = 231 of 287) and a high psychosocial burden group (n = 56 of 287). The low psychosocial burden group retained remission longer (hazard ratio 0.51 [0.35–0.73]). In the CLPM, temporal relationships between psychosocial well‐being and DAS28‐CRP were complex, bidirectional, and disease‐phase dependent.ConclusionSuboptimal psychosocial well‐being and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, 1 in 5 patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.

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