The Impact of mHealth-Based Continuous Care on Disease Knowledge, Treatment Compliance, and Serum Uric Acid Levels in Chinese Patients With Gout: Randomized Controlled Trial.

Background: In patients with gout, suboptimal management refers to a lack of disease knowledge, low treatment compliance, and inadequate control of serum uric acid (SUA) levels. Several studies have shown that continuous care is recommended for disease management in patients with gout. However, in China, the continuous care model commonly used for patients with gout requires significant labor and time costs, and its efficiency and coverage remain low. Mobile health (mHealth) may be able to address these issues. Objective: This study aimed to explore the impact of mHealth-based continuous care on improving gout knowledge and treatment compliance and reducing SUA levels. Methods: This study was a single-center, single-blind, and parallel-group randomized controlled trial. Participants were recruited at the West China Hospital of Sichuan University in Chengdu, China, between February 2021 and July 2021 and were randomly assigned to the intervention and control groups. The intervention group received continuous care via an mHealth app, which includes modules for health records, 24 weeks of gout-related health education materials, and interactive support. The control group received routine continuous care, including face-to-face health education, paper-based health education materials consistent with the content for the intervention group, and telephone consultations initiated by the patient. Follow-up was conducted at 6 months. Participants' gout knowledge levels and treatment compliance were measured at baseline and the 12th and 24th weeks, and participants' SUA levels were measured at baseline and the 24th week. The intention-to-treat principle and a generalized estimating equation model were used to test the effect of the intervention. Results: Overall, 258 potential participants underwent eligibility assessments, and 120 were recruited and randomized into the intervention (n=60, 50%) and control (n=60, 50%) groups. Of the 120 participants, 93 (77.5%) completed the 24-week study. The 2 groups had no significant differences in sociodemographic or clinical characteristics, and the baseline measurements were comparable (all P>.05). Compared with the control group, the intervention group exhibited a significant improvement in gout knowledge levels over time (ß=0.617, 95% CI 0.104-1.129; P=.02 and ß=1.300, 95% CI 0.669-1.931; P<.001 at the 12th and 24th weeks, respectively). There was no significant difference in treatment adherence between the 2 groups at the 12th week (ß=1.667, 95% CI -3.283 to 6.617; P=.51), while a statistical difference was observed at the 24th week (ß=6.287, 95% CI 1.357-11.216; P=.01). At the 24th week, SUA levels in both the intervention and control groups were below baseline, but there was no significant difference in SUA changes between the 2 groups (P=.43). Conclusions: Continuous care based on the mHealth app improved knowledge levels and treatment compliance among patients with gout. We suggest incorporating this intervention modality into standard continuous care for patients with gout.

Long-term clinical outcomes in early rheumatoid arthritis that was treated-to-target in the BeSt and IMPROVED studies.

OBJECTIVES: To assess disease outcomes after 20 and 12 years of patients with rheumatoid (RA) or undifferentiated arthritis (UA), treated-to-target in the BeSt and IMPROVED trials. METHODS: In BeSt (inclusion 2000-2002, duration 10 years), 508 patients with early RA were randomized to: 1. sequential monotherapy, 2. step-up combination therapy, 3. initial csDMARD combination therapy, 4. initial bDMARD/csDMARD combination therapy. The treatment target was low disease activity (DAS ≤ 2.4).In IMPROVED (inclusion 2007-2010, duration 5 years), 610 patients with early RA/UA started MTX with prednisone bridging. The treatment target was remission (DAS < 1.6). Patients not in early remission were randomized to 1. csDMARD combination therapy or 2. bDMARD/csDMARD combination therapy.Between 2019-2022, these patients were invited for long-term follow-up. RESULTS: One-hundred-fifty-three ex-Best and 282 ex-IMPROVED patients participated in the follow-up study after median 12 and 20 years since study start.In ex-BeSt and ex-IMPROVED patients the rate of low disease activity was 91%, and 68% were in DAS remission. Median SHS was 14.0 in ex-BeSt (IQR 6.0-32.5; progression since end BeSt 6.0, IQR 2.0-12.5) and 8 in ex-IMPROVED participants (IQR 3-16; progression since end IMPROVED 4, IQR 2-9). Mean HAQ was 0.8 ± 0.6 in ex-BeSt (change since end BeSt: 0.3 ± 0.5) and 0.6 ± 0.6 in ex-IMPROVED participants (change since end IMPROVED: 0.06 ± 0.5). CONCLUSION: At 12/20 years after treatment start, the majority of RA and UA patients who had been treated to target low DAS or DAS remission were in DAS remission and had limited functional disability. Radiographic damage progression was mild although not completely suppressed.

Evaluation of a hybrid telehealth care pathway for patients with axial spondyloarthritis including self-sampling at home: results of a longitudinal proof-of-concept mixed-methods study (TeleSpactive).

Patients with axial spondyloarthritis (axSpA) require close monitoring to achieve the goal of sustained disease remission. Telehealth can facilitate continuous care while relieving scarce healthcare resources. In a mixed-methods proof-of-concept study, we investigated a hybrid telehealth care axSpA pathway in patients with stable disease over 6 months. Patients used a medical app to document disease activity (BASDAI and PtGA bi-weekly, flare questionnaire weekly). To enable a remote ASDAS-CRP (TELE-ASDAS-CRP), patients used a capillary self-sampling device at home. Monitoring results were discussed and a decision was reached via shared decision-making whether a pre-planned 3-month on-site appointment (T3) was necessary. Ten patients completed the study, and eight patients also completed additional telephone interviews. Questionnaire adherence was high; BASDAI (82.3%), flares (74.8%) and all patients successfully completed the TELE-ASDAS-CRP for the T3 evaluation. At T3, 9/10 patients were in remission or low disease activity and all patients declined the offer of an optional T3 on-site appointment. Patient acceptance of all study components was high with a net promoter score (NPS) of +50% (mean NPS 8.8 ± 1.5) for self-sampling, +70% (mean NPS 9.0 ± 1.6) for the electronic questionnaires and +90% for the T3 teleconsultation (mean NPS 9.7 ± 0.6). In interviews, patients reported benefits such as a better overview of their condition, ease of use of telehealth tools, greater autonomy, and, most importantly, travel time savings. To our knowledge, this is the first study to investigate a hybrid approach to follow-up axSpA patients including self-sampling. The positive results observed in this scalable proof-of-concept study warrant a larger confirmatory study.

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age.

Objectives: To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Methods: Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. Results: LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. Conclusions: It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.

Comparing Achievement of National Psoriasis Foundation Treatment Targets among Patients with Plaque Psoriasis Treated with Ixekizumab versus Other Biologics in Clinical and Real-World Studies.

INTRODUCTION: The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week 12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This post hoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. METHODS: Outcomes were evaluated at week 12 for patients with moderate-to-severe plaque psoriasis from four head-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher's exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). RESULTS: Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week 12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week 12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week 12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week 12 versus brodalumab (BROD). CONCLUSION: Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week 12 compared with those treated with other biologics. TRIAL REGISTRATION: UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207).

First validation of the childhood lupus low disease activity state (cLLDAS) definition in a real-life longitudinal cSLE cohort.

OBJECTIVES: To validate the childhood lupus low disease activity state (cLLDAS) definition in cSLE by describing differences in time to reach first adult LLDAS (aLLDAS) versus cLLDAS. Secondly, to analyse positive and negative predictors for maintaining cLLDAS for at least 50% of follow-up time (cLLDAS-50) and for the occurrence of damage. METHODS: Prospective longitudinal data from a cSLE cohort were analysed. Used definitions were: aLLDAS according to Franklyn, cLLDAS by cSLE treat-to-target (T2T) Task Force, disease activity score by SLEDAI -2 K and damage by SLICC damage index. RESULTS: Fifty cSLE patients were studied, with a median follow-up of 3.1 years. Each patient reached aLLDAS and cLLDAS at least once. Mean time to reach first aLLDAS/cLLDAS was 8.2/9.0 months, respectively. For 22/42 patients the mean steroid-dose related delay to reach first cLLDAS was 6.2 months. 58% of patients were able to maintain cLLDAS-50. Time to first cLLDAS (OR 0.8, p = 0.013) and higher number of flares (OR 0.374, p = 0.03) were negative predictors to maintain cLLDAS-50. Damage occurred in 34% of patients (23.5% steroid-related), in 64.7% within one year after diagnosis. African/Afro-Caribbean ethnicity, neuropsychiatric involvement and ever use of a biologic were significant predictors for damage. CONCLUSION: Time to reach cLLDAS in cSLE differs from time to (a)LLDAS, which validates the new cLLDAS definition. Attaining cLLDAS-50 was difficult in real-life. This cohort shows the high risk for early damage in cSLE. T2T with earlier focus on steroid-tapering and starting steroid-sparing drugs seems important to prevent (steroid-related) damage in cSLE.

Upadacitinib in Crohn's disease.

INTRODUCTION: The small molecule and oral selective and reversible Janus kinase (JAK) inhibitor upadacitinib has been approved for the treatment of moderate to severe active Crohn's disease (CD) in adult patients since April 2023 by EMA/FDA. AREAS COVERED: The approval is based on the two induction studies a maintenance study showing that upadacitinib induction and maintenance therapy was superior to placebo. The approval of upadacitinib in CD expands the therapeutic armamentarium for the management of inflammatory bowel diseases (IBD). Upadacitinib is the first and only JAK inhibitor approved in patients with CD and provides a novel mechanism of action and the first advanced oral treatment option for patients with CD. Upadacitinib is approved for the treatment of other immunologically mediated disorders, including ulcerative colitis, rheumatoid arthritis, psoriasis arthritis, axial spondylarthritis, ankylosing spondylitis, and atopic dermatitis. Treatment of atopic dermatitis has been approved from the age of 12 years. EXPERT OPINION: Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn's disease. Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD.

Shifting from the treat-to-target to the early highly effective treatment approach in patients with multiple sclerosis - real-world evidence from Germany.

Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective: To assess the adoption of the early highly effective treatment (EHT) compared to the treat-to-target treatment approach with the option of escalating treatment efficacy over time in Germany based on real-world evidence data. Design: Patient-level pharmacy dispensing data from the Permea platform were analysed from 2020 to 2022. Methods: In total, 29,529 therapy beginners (>18 years) were included to analyse shifts in treatment approaches over time and switching behaviour. Medication classification adhered to the German Society of Neurology guidelines and designated fumarates, glatiramer acetate, teriflunomide and interferons as low-efficacy category 1 medications; cladribine and S1P-modulators as medium-efficacy category 2 medications; and alemtuzumab, natalizumab, ocrelizumab, ofatumumab and rituximab (off-label) as high-efficacy category 3 medications. Results: Our results show that 70.0% of patients redeemed their first prescription for category 1 medication, 16.3% for category 2 and 13.7% for category 3 medications. The proportion of prescriptions filled shifted from 2020 to 2022 with a decrease of 14.7% for category 1 drugs and an increase of 12.5% for category 3 drugs. 93.2% of patients stayed on their initially prescribed medication category. 3.2% of category 1 and 3.7% of category 2 therapy beginners escalated to category 3 medication. 3.4% of category 3 medication users de-escalated their treatment to category 1 or category 2. Conclusion: While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by German guidelines, MS providers increasingly adopt the EHT approach.

Association between P1NP value and increases in bone mineral density in patients with postmenopausal osteoporosis treated with romosozumab.

OBJECTIVES: The present study aimed to investigate the effectiveness of treatment with romosozumab for one year and association between bone turnover markers and changes in bone mineral density (BMD) in patients with postmenopausal osteoporosis (PMO). METHODS: Participants were 53 treatment-naïve PMO patients. Correlations of percent changes (Δ) in lumbar (L) and total hip (TH) BMD 12 months after initiating romosozumab with baseline demographic factors and parameters of N-terminal propeptide of type 1 collagen (P1NP) and tartrate-resistant acid phosphatase (TRACP)-5b at baseline and months 1, 3 and 6 were assessed. Multiple regression analysis was performed on factors significantly correlated with ΔL-BMD and ΔTH-BMD at month 12. RESULTS: ΔL-BMD and ΔTH-BMD at month 12 were 17.5% and 8.1%, respectively. Multiple regression analysis revealed that a high P1NP value at month 3 predicted large increases in L-BMD and TH-BMD at month 12. High total amount of P1NP values from baseline to month 6 was associated with large increases in L-BMD and TH-BMD at month 12, and was most strongly correlated with the P1NP value at month 3. CONCLUSIONS: A high P1NP value at month 3 predicted large increases in both L-BMD and TH-BMD at month 12 in PMO patients treated with romosozumab.

Treat to target in Crohn's disease: A practical guide for clinicians.

A treat-to-target (T2T) approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II guidelines specify short, intermediate, and long-term treatment goals, documenting specific treatment targets to be achieved at each of these timepoints. Scheduled appraisal of Crohn's disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified. Consensus treatment targets in Crohn's disease comprise combination clinical and patient-reported outcome remission, in conjunction with biomarker normalisation and endoscopic healing. Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing, clinicians must consider that this may not always be appropriate, acceptable, or achievable in all patients. This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets. The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques, particularly intestinal ultrasound, holds great promise; as do emerging treatment targets such as transmural healing. Two randomised clinical trials, namely, CALM and STARDUST, have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn's disease. Findings from these studies reflect that patient subgroups and Crohn's disease characteristics likely to benefit most from a T2T approach, remain to be clarified. Moreover, outside of clinical trials, data pertaining to the real-world effectiveness of a T2T approach remains scare, highlighting the need for pragmatic real-world studies. Despite the obvious promise of a T2T approach, a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake. This highlights the need to describe strategies, processes, and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice. Hence, this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn's disease.

IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

A prospective survey on therapeutic inertia in psoriatic arthritis (OPTI'PsA).

OBJECTIVES: Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA). METHODS: Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases ('oligoarthritis', 'enthesitis', 'polyarthritis', 'neoplastic history', 'cardiovascular risk') requiring treatment OPTImization, and two 'control' cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment-according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA. RESULTS: One hundred and one rheumatologists completed this OPTI'PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were 'oligoarthritis' and 'enthesitis' with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty ('polyarthritis in relapse', 'neoplastic history' and 'cardiovascular risk') generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment. CONCLUSION: The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia.

Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review.

OBJECTIVES: To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA. METHODS: A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators. RESULTS: Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each). CONCLUSIONS: This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.

Harmonizing Medicine and Surgery in the Pursuit of Boolean Remission: A Rheumatological Magnum Opus.

Rheumatic diseases encompass a diverse group of musculoskeletal conditions that often lead to inflammation, pain, and significant limitations in patients' lives. While traditional treatment approaches have primarily centered on medications to control symptoms, recent developments have introduced the concept of Boolean remission. Boolean remission offers a comprehensive evaluation of disease activity by considering clinical, biochemical, and patient-reported outcomes. This narrative review explores the multifaceted landscape of Boolean remission in the context of rheumatic diseases, with a focus on rheumatoid arthritis (RA), as it remains a substantial clinical challenge. The review outlines the definition, criteria, historical context, and development of Boolean remission, shedding light on its emergence as a more patient-centered and stringent treatment goal. The role of pharmacological interventions, including immunomodulators and biologics, in achieving Boolean remission is discussed, emphasizing the significance of treatment protocols that encompass regular monitoring, medication adjustment, shared decision-making, and patient education. Surgical interventions, such as joint replacements and synovectomies, complement medication-based strategies when joint damage becomes severe, with adherence to surgical protocols ensuring sustained Boolean remission. The integration of medicine and surgery through integrated care models and interdisciplinary teams is examined as a critical aspect of optimizing patient outcomes. Boolean remission's broader impact on healthcare policies and clinical trial endpoints is explored, underscoring its growing significance in rheumatic disease management. The review concludes by looking toward the future, where emerging technologies, biomarkers, and personalized medicine approaches hold promise in refining Boolean remission criteria and making it a more attainable and impactful treatment goal. Policy implications suggest the integration of Boolean remission into healthcare quality metrics, incentivizing healthcare providers to prioritize this rigorous standard of care. Boolean remission represents a pivotal shift in the holistic and patient-centered management of rheumatic diseases, offering hope for improved patient outcomes and enhanced quality of life in this challenging clinical landscape.

Impact of serological activity on flare following clinically inactive disease and remission in childhood-onset systemic lupus erythematosus.

OBJECTIVES: To assess the association between serological activity (SA) and clinical inactivity in SLE and to investigate whether SA predicts flare after clinically inactive disease (CID) and remission. METHODS: Longitudinal data of children from 3 paediatric rheumatology referral centres were retrospectively reviewed. CID was defined as clinical SLEDAI = 0 in patients with a prednisolone dose < 15 mg/day. A modified DORIS remission on treatment criteria was used to determine remission. RESULTS: Of the 124 patients included, 89.5% displayed SA at onset. Through follow-up, the rate of SA decreased to 43.3% at first CID and 12.1% at remission. Among patients with CID, 24 (20.7%) experienced a moderate to severe flare before the attainment ofremission. While previous proliferative lupus nephritis (OR : 10.2, p: 0.01) and autoimmune haemolytic anaemia (OR : 6.4, p: 0.02) were significantly associated with an increased odds of flare after CID, SA at CID was not associated with flare. In contrast, 21 (19.6%) patients experienced a flare in a median of 18 months after remission. Hypocomplementemia (OR : 9.8, p: 0.02) and a daily hydroxychloroquine dose < 5 mg/kg (OR : 5.8, p: 0.02) at remission significantly increased the odds of flare. CONCLUSION: SA increases the odds of flare at remission but not at CID. Suboptimal dosing of hydroxychloroquine should be avoided, especially in children with SA in remission to lower the risk of flares.

Artritis reumatoide / Rheumatoid arthritis

La artritis reumatoide (AR) es una enfermedad inflamatoria crónica multisistémica de etiología desconocida y de naturaleza autoinmune que afecta predominantemente a las articulaciones periféricas de forma simétrica. Aunque se ha avanzado mucho en la comprensión de su fisiopatología, su etiología sigue siendo desconocida. El factor de necrosis tumoral (TNF)-α y la interleucina (IL)-6, juegan un papel importante en la patogénesis y la perpetuación de la inflamación en la AR. La presencia de anticuerpos antipéptidos citrulinados ayuda en el diagnóstico en pacientes con poliartritis indiferenciadas y se relaciona con una evolución más agresiva de la AR. La evolución natural de la AR causa deformidad articular y discapacidad, además de una reducción de la esperanza de vida, por aumento del riesgo cardiovascular, afectación pulmonar, infecciones, iatrogenia o tumores. El diagnóstico precoz y la utilización de fármacos dirigidos que buscan la remisión temprana han mejorado sustancialmente el pronóstico de la AR (AU)

Rheumatoid arthritis (RA) is a chronic inflammatory multisystemic disease of unknown etiology and autoimmune nature that predominantly affects peripheral joints in a symmetrical fashion. Although much progress has been made in understanding the pathophysiology of RA, its etiology remains unknown. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 play the important roles in the pathogenesis and maintenance of inflammation in RA. The presence of anti-citrullinated peptide antibodies aids in the diagnosis in patients with undifferentiated polyarthritis and is associated with a more aggressive RA. The natural history of RA causes joint deformity and disability, as well as reduced life expectancy, both due to increased cardiovascular risk, pulmonary involvement, infections, iatrogenesis or tumors. Early diagnosis and the use of targeted drugs to induce early remission have improved the RA prognosis (AU)

Treat-to-Target and Regular Surveillance of Inflammatory Bowel Disease Are Associated with Low Incidence and Early-Stage Detection of Malignancies: A Retrospective Cohort Study.

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), increase the risk of malignancies, particularly colorectal cancer (CRC). We aimed to assess the incidence of malignancies in IBD patients managed using a treat-to-target approach and recommended surveillance. We retrospectively searched the electronic databases of two tertiary IBD centers in Milan from 2010 to 2019 for new diagnoses of malignancy in patients with pre-existing IBD. A total of 5239 patients with a follow-up of 19,820 years were included. In total, 71 malignancies were diagnosed in 70 patients (38 CD, 32 UC) with a mean age of 52.9 years, of whom 64% were former or active smokers. The annual incidence of all malignancies was 358 per 100,000 patient years (95% CI 275-444), and the standardized incidence rate (SIR) was 0.93 (95% CI 0.73-1.16). Gastrointestinal cancers were the most frequent (n = 17, 23.9%), in particular, CRC (n = 9), with an incidence of 45 per 100,000 (95% CI 15-74) and an SIR of 1.18 (95% CI 0.54-2.09). CRC occurred mainly in UC patients (6/8), while small bowel cancer was seen in CD patients (5/9). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers. No significant difference in incidence was found between CD or UC. Death occurred in nine patients (11%) and was due to cancer in eight of these cases, two of which were IBD-related. Most malignancies included in the surveillance were diagnosed at early (I-II) stages (20 vs. 4, p < 0.05). In patients with IBD, treat-to-target and strict surveillance were associated with a low incidence of cancer, similar to that of the general population, and the detection of malignancies at an early stage.

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.

Kidney involvement in systemic lupus erythematosus: From the patient assessment to a tailored treatment.

In the last few years, several studies have provided new evidence for the diagnosis, management, and follow-up of patients with lupus nephritis. Evidence showing dissociation between clinical and histological findings has prompted reevaluation of the role of the kidney biopsy as a tool for diagnosis and follow-up. In therapeutics, four immunosuppressive schemes now have supporting evidence for use as initial therapy. Current challenges include individualized selection of the best immunosuppressive regimen, an unmet need for non-invasive biomarkers of disease activity to inform treatment responses and guide subsequent therapy, holistic patient management in this complex, multisystem disease, and ultimately the development of more targeted therapies directed at specific effector pathways driving glomerular inflammation and damage in order to improve treatment response. In this communication, we review the diagnostic and therapeutic approach to lupus nephritis, as well as evaluation of response to therapy and disease control.