EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

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.

Effect of Belimumab on Preventing de novo Renal Lupus Flares.

Introduction: Belimumab was recently approved for treating lupus nephritis (LN), yet de novo LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative. Methods: We evaluated belimumab efficacy in preventing de novo renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis. Results: Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. Asian origin (Adjusted Hazard Ratio [HRadj]: 1.97; 95% confidence interval [CI]: 1.32-2.94; P = 0.001), positive baseline anti-double stranded DNA (anti-dsDNA) levels (HRadj: 1.32; 95% CI: 1.07-1.63; P = 0.008), and increasing mean prednisone dose during follow-up (HRadj: 1.03; 95% CI: 1.02-1.04; P < 0.001) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg monthly) yielded a nearly 3-fold lower hazard of de novo renal flare (HRadj: 0.38; 95% CI: 0.20-0.73; P = 0.004). Subcutaneous (SC) belimumab (200 mg weekly) also yielded a lower hazard (HRadj.: 0.69; 95% CI: 0.54-0.88; P = 0.003). The labeled IV dose (10 mg/kg monthly) conferred no clear protection (HRadj.: 0.74; 95% CI: 0.50-1.09; P = 0.127). Conclusion: We corroborated the substantial vulnerability of the Asian SLE population to renal affliction. Add-on low-dose IV belimumab (1 mg/kg) and SC belimumab appeared protective against renal flares in nephritis-naïve patients with SLE. The approved IV dose (10 mg/kg) yielded no clear protection.

From systemic lupus erythematosus to lupus nephritis: The evolving road to targeted therapies.

Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage.

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial.

OBJECTIVE: To characterise the safety and efficacy of anifrolumab in active lupus nephritis (LN) through year 2 of the phase II randomised, double-blind Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP)-LN trial (NCT02547922) of 2 anifrolumab dosing regimens versus placebo. METHODS: Patients received intravenous anifrolumab 900 mg for the first 3 doses followed by 300 mg anifrolumab (intensified regimen (IR)), 300 mg anifrolumab (basic regimen (BR)) or placebo every 4 weeks throughout. To continue into Year 2, patients must have achieved at least partial renal response and a glucocorticoid tapering target. RESULTS: Of 147 randomised patients, 101 completed Year 1 study treatment; of these, 75 (74%) continued into Year 2 (anifrolumab IR: n=29, BR: n=23 and placebo: n=23). During Year 2, 72% of patients reported ≥1 adverse event (AE); serious AEs were reported in 6.9%, 8.7% and 8.7% of patients (anifrolumab IR, BR and placebo, respectively); 3 patients discontinued treatment due to an AE (anifrolumab IR: n=2 and placebo: n=1) and herpes zoster was reported in 2 patients (anifrolumab IR: n=1 and BR: n=1). The study was ongoing at the start of the pandemic, but no COVID-19 cases were reported. Of the 145 patients receiving treatment, more patients on the IR attained complete renal response at Week 104 compared with those on BR or placebo (27.3% vs 18.6% and 17.8%) and simultaneously achieved sustained glucocorticoid tapering (IR: 25.0%; BR: 18.6% and placebo: 17.8%). The improvements in estimated glomerular filtration rate were numerically larger in both anifrolumab groups versus placebo. CONCLUSIONS: The safety and tolerability profile through Year 2 of TULIP-LN was generally consistent with Year 1, with promising efficacy results for the anifrolumab IR regimen. Collectively, the results support further investigation of an anifrolumab intensified dosing regimen in larger populations of patients with active proliferative LN. TRIAL REGISTRATION NUMBER: NCT02547922.

Worse long-term renal outcome of lupus nephritis patients of African descent living in Europe.

INTRODUCTION: Prognosis of lupus nephritis (LN) among patients of African descent living in Europe has been understudied. METHODS: In a retrospective study performed in two European university hospitals, we compared the prognosis of LN in patients of African descent or Caucasians. Remission was defined as a urine protein to creatinine (uP/C) ratio<0.5 g/g and a serum creatinine value<120% of baseline. Renal relapse was defined as the reappearance of a uP/C>1 g/g, leading to a repeat kidney biopsy and/or immunosuppressive treatment change. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate≤60 mL/min/1.73 m2. Adherence was retrospectively assessed through medical files and/or hydroxychloroquine level measurements. RESULTS: 52 patients of African descent and 85 Caucasian patients were included in this analysis. Class III and isolated class V LN were more common among patients of African descent. Time to first renal remission did not differ between ethnic subgroups. By contrast, patients of African descent suffered from earlier renal flares, CKD was more common and time to CKD was shorter after a flare. In a multivariate analysis, African ancestry was an independent risk factor for progression to CKD. We observed no significant difference in non-adherence to treatment between the two groups. CONCLUSION: LN patients of African descent have worse renal outcomes, mainly explained by a higher rate of renal flare.

Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study.

BACKGROUND AND OBJECTIVES: In the BLISS-LN study, belimumab improved kidney outcomes in adult patients with active lupus nephritis. This 28-week open-label extension of BLISS-LN assessed belimumab's safety and efficacy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eligible patients completing BLISS-LN received monthly intravenous belimumab 10 mg/kg plus standard therapy. End points included safety, open-label week 28 primary efficacy renal response (urine protein-creatinine ratio [UPCR] ≤0.7, eGFR no more than 20% below open-label baseline value or ≥60 ml/min per 1.73 m2, no prohibited medications) and complete renal response (UPCR <0.5, eGFR no more than 10% below open-label baseline value or ≥90 ml/min per 1.73 m2, no prohibited medications), and UPCR and eGFR by visit. Responses were also analyzed post hoc using the double-blind phase criteria. RESULTS: Of 257 enrolled patients, 255 were treated (safety population: n=123 switched from placebo-to-belimumab; n=132 remained on belimumab); 245 (97%) patients completed the study. Adverse events and serious adverse events were experienced by 62% and 4% of placebo-to-belimumab patients, respectively, and by 70% and 8% of belimumab-to-belimumab patients, respectively. One death occurred in the placebo-to-belimumab group. From open-label baseline to week 28, increases occurred in the proportions of patients achieving primary efficacy renal response (placebo-to-belimumab: from 60% to 67%; belimumab-to-belimumab: from 70% to 75%) and complete renal response (placebo-to-belimumab: from 36% to 48%; belimumab-to-belimumab: from 48% to 62%). Based on double-blind phase criteria, changes also occurred in the proportions achieving primary efficacy renal response (placebo-to-belimumab: from 54% to 53%; belimumab-to-belimumab: from 66% to 52%) and complete renal response (placebo-to-belimumab: from 34% to 35%; belimumab-to-belimumab: from 46% to 41%). The seeming decrease in response rates in the belimumab-to-belimumab groups was attributed to discontinuations/administration of glucocorticoids for non-SLE reasons as opposed to nephritis. Median UPCR and eGFR values were similar at open-label baseline and week 28. CONCLUSIONS: No new safety signals were identified, and efficacy was generally maintained throughout the open-label phase. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: BLISS-LN, NCT01639339.

Controversies in Systemic Lupus Erythematosus 2021: Changing the Paradigm in the Management of Lupus Nephritis.

ABSTRACT: Lupus nephritis (LN) affects about a third of patients with systemic lupus erythematosus. Although the use of conventional therapy has significantly improved the prognosis of LN, the response to treatment remains suboptimal, with high rates of relapse and the occurrence of end-stage kidney disease. The implementation of new diagnostic and treatment strategies aimed at improving these outcomes represents a necessary paradigm shift in the management of LN.Herein, we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the virtual congress of the Pan American League of Associations for Rheumatology (PANLAR) and which was organized by the PANLAR Lupus Study Group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on August 15, 2021.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

New Treatment Options in Lupus Nephritis.

The aim of this study is to report major recent progresses in the treatment of lupus nephritis (LN). Results of controlled randomized trials are discussed in view of the unmet needs in the field. Current treatments of LN are not satisfactory, with a disappointing proportion of 20-30% of patients achieving complete renal response within 6-12 months, and 5-20% developing end-stage kidney disease within ten years. Two drugs (belimumab and voclosporin) have been officially registered by the medical agencies as add on treatment of LN, a first-in-history success after decades of use of non-registered drugs and trial failures. Other targeted therapies (obinutuzumab and anifrolumab) are currently tested in Phase III trials, after interesting results in Phase II studies. Unanswered questions related to the use of these new drugs are discussed. Recent trials have opened new avenues for the treatment of LN which will hopefully reduce the rate of chronic kidney disease.

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis.

OBJECTIVE: To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. METHODS: This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), intensified regimen (IR, 900 mg ×3, 300 mg thereafter) or placebo, alongside standard therapy (oral glucocorticoids, mycophenolate mofetil). The primary endpoint was change in baseline 24-hour urine protein-creatinine ratio (UPCR) at week (W) 52 for combined anifrolumab versus placebo groups. The secondary endpoint was complete renal response (CRR) at W52. Exploratory endpoints included more stringent CRR definitions and sustained glucocorticoid reductions (≤7.5 mg/day, W24-52). Safety was analysed descriptively. RESULTS: Patients received anifrolumab BR (n=45), IR (n=51), or placebo (n=49). At W52, 24-hour UPCR improved by 69% and 70% for combined anifrolumab and placebo groups, respectively (geometric mean ratio=1.03; 95% CI 0.62 to 1.71; p=0.905). Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which provided suboptimal exposure. Numerically more patients treated with anifrolumab IR vs placebo attained CRR (45.5% vs 31.1%), CRR with UPCR ≤0.5 mg/mg (40.9% vs 26.7%), CRR with inactive urinary sediment (40.9% vs 13.3%) and sustained glucocorticoid reductions (55.6% vs 33.3%). Incidence of herpes zoster was higher with combined anifrolumab vs placebo (16.7% vs 8.2%). Incidence of serious adverse events was similar across groups. CONCLUSION: Although the primary endpoint was not met, anifrolumab IR was associated with numerical improvements over placebo across endpoints, including CRR, in patients with active lupus nephritis. TRIAL REGISTRATION NUMBER: NCT02547922.

Treat-to-Target in Lupus Nephritis. What is the Role of the Repeat Kidney Biopsy?

Kidney involvement, termed lupus nephritis (LN), develops in 35-60% of patients with systemic lupus erythematosus, often early during the disease course. When not treated promptly and efficiently, LN may lead to rapid and severe loss of kidney function, being the reason why it is considered one of the most severe lupus manifestations. Despite improved pharmacotherapy, 5-20% of LN patients develop end-stage kidney disease within ten years from the LN diagnosis. While the principal ground of LN therapy is prevention of renal function worsening, resembling a race against nephron loss, consensual agreement upon outcome measures and clinically meaningful short- and long-term targets of LN therapy have yet to be determined. Literature points to the importance of inclusion of tissue-based approaches in the determination of those targets, and evidence accumulates regarding the importance of per-protocol repeat kidney biopsies in the evaluation of the initial phase of therapy and prediction of long-term renal prognosis. The latter leads to the hypothesis that the information gleaned from repeat biopsies may contribute to optimised therapeutic decision making, and, therefore, increased probability to attain complete renal response in the short term, and a more favourable renal prognosis within a longer prospect. The multinational project ReBioLup was recently designed to serve as a key contributor to form evidence about the role of per-protocol repeat biopsies in a randomised fashion and aspires to unify the global LN community towards improved kidney and patient survival.

From sequential to combination and personalised therapy in lupus nephritis: moving towards a paradigm shift?

The current treatment paradigm in lupus nephritis consists of an initial phase aimed at inducing remission and a subsequent remission maintenance phase. With this so-called sequential treatment approach, complete renal response is achieved in a disappointing proportion of 20-30% of the patients within 6-12 months, and 5-20% develop end-stage kidney disease within 10 years. Treat-to-target approaches are detained owing to uncertainty as to whether the target should be determined based on clinical, histopathological, or immunopathological features. Until reliable non-invasive biomarkers exist, tissue-based evaluation remains the gold standard, necessitating repeat kidney biopsies for treatment evaluation and therapeutic decision-making. In this viewpoint, we discuss the pros and cons of voclosporin and belimumab as add-on agents to standard therapy, the first drugs to be licenced for lupus nephritis after recent successful randomised phase III clinical trials. We also discuss the prospect of obinutuzumab and anifrolumab, also on top of standard immunosuppression, currently tested in phase III trials after initial auspicious signals. Undoubtably, the treatment landscape in lupus nephritis is changing, with combination treatment regimens challenging the sequential concept. Meanwhile, the enrichment of the treatment armamentarium shifts the need from lack of therapies to the challenge of how to select the right treatment for the right patient. This has to be addressed in biomarker surveys along with tissue-level mapping of inflammatory phenotypes, which will ultimately lead to person-centred therapeutic approaches. After many years of trial failures, we may now anticipate a heartening future for patients with lupus nephritis.

2021 DORIS definition of remission in SLE: final recommendations from an international task force.

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.

High p16INK4a, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis.

OBJECTIVES: Because a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome. METHODS: We enumerated the number of cells positive for p16INK4a protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN. We tested for an association of p16INK4a with renal fibrosis, CD8+ T cell infiltration, systemic disease and renal function at baseline and at 5 years. RESULTS: The presence of p16INK4a-positive cells was significantly associated with lower estimated glomerular filtration rate at baseline and 5 years post-treatment, independently of patient demographics and systemic disease parameters. It was also associated with higher baseline renal fibrosis and CD8+ T cell infiltration. Interestingly, we observed marked spatial co-distribution of glomerular p16INK4a-positive cells with CD8+ T cells. CONCLUSION: We demonstrate, for the first time, that LN biopsies characterised by renal impairment display increased p16INK4a-positive cells, associated with higher fibrosis and CD8+ T cell infiltration. Cellular senescence may represent a kidney-intrinsic disease mechanism and potentially, a novel therapeutic target in LN.

Absence of renal remission portends poor long-term kidney outcome in lupus nephritis.

BACKGROUND: The very long-term consequences of absence of remission in lupus nephritis (LN) remain understudied. METHODS: In this retrospective analysis, we studied a selected cohort of 128 patients with biopsy-proven class III, IV or V incident LN followed for a median period of 134 months (minimum 25). Remission was defined as a urine protein to creatinine (uP:C) ratio <0.5 g/g and a serum creatinine value <120% of baseline. Renal relapse was defined as the reappearance of a uP:C >1 g/g, leading to a repeat kidney biopsy and treatment change. Poor long-term renal outcome was defined as the presence of chronic kidney disease (CKD). RESULTS: Twenty per cent of patients never achieved renal remission. Their baseline characteristics did not differ from those who did. Absence of renal remission was associated with a threefold higher risk of CKD (48% vs 16%) and a 10-fold higher risk of end-stage renal disease (20% vs 2%). Patients achieving early remission had significantly higher estimated glomerular filtration rate (eGFR) at last follow-up compared with late remitters. Accordingly, patients with CKD at last follow-up had statistically longer time to remission. Among patients who achieved remission, 32% relapsed, with a negative impact on renal outcome, that is, lower eGFR values and higher proportion of CKD (33% vs 8%). CONCLUSION: Early remission should be achieved to better preserve long-term renal function.

Incidence, prevalence and long-term progression of Goh algorithm rated interstitial lung disease in systemic sclerosis in two independent cohorts in flanders: A retrospective cohort study.

OBJECTIVES: The epidemiology of interstitial lung disease (ILD) in systemic sclerosis (SSc) in Belgium is unknown. In literature, its prevalence varies between 19% and 52% in limited/diffuse cutaneous SSc (LcSSc/DcSSc). However, its prevalence in "early" SSc (pre-clinically overt SSc without [yet] skin involvement), nor its incidence rate in SSc (LcSSc/DcSSc/"early" SSc) has ever been described. Against this background, we aimed to determine the prevalence/incidence (rate) and progression of ILD in SSc. METHODS: 12-year follow-up data of consecutive SSc patients, included in two Flemish cohorts (University Hospitals Ghent and Leuven), were retrospectively analysed. ILD was classified according to the simplified Goh algorithm. Progression of ILD was defined as a relative decline of FVC ≥10%, a combined relative decline of FVC 5-10% and DLCO ≥15%, or as an increase in HRCT extent. RESULTS: 722 patients (60% LcSSc/ 20% DcSSc/ 20% "early" SSc, median (IQR) follow-up 39 [12-80] months) had baseline HRCT. 243 were rated to have ILD at baseline and 39 during follow-up (prevalence of 34%/ incidence rate of 20.3/1000PY, 95%CI:14.5-27.8). Amongst those with baseline ILD, 60% had lung functional progression at five years of follow-up. In the "early" SSc subgroup, eight patients were rated to have ILD at baseline and three during follow-up (prevalence of 6%/ incidence rate of 5.8/1000 PY, 95%CI:1.2-17.0). CONCLUSION: Both LcSSc and DcSSc patients should be monitored for ILD evolution. The low prevalence and incidence of ILD in the "early" SSc subgroup may instruct future decisions on the construction of uniform patient follow-up pathways in "early" SSc.

Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients.

BACKGROUND: Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. METHODS: A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2-4). RESULTS: The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). CONCLUSION: We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.