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treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn.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.

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.

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.

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.

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.

What are the topics you care about making trials in lupus more effective? Results of an Open Space meeting of international lupus experts.

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs.

Management of Lupus Nephritis.

Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials.

Very Late-Onset Systemic Lupus Erythematosus as Unusual Cause of Reversible Functional and Cognitive Impairments in an Octogenarian Patient.

While functional decline is a common syndrome in geriatric medicine, the diagnosis of the underlying disease can be complex. We present a case of very late-onset systemic lupus erythematosus with fever, arthritis, lymphadenopathy, sicca syndrome, pleurisy, renal impairment and reversible functional and cognitive impairments. Prompt improvement was observed on prednisolone and hydroxychloroquine. LEARNING POINTS: Systemic lupus erythematosus (SLE) rarely occurs in octogenarian patients.In such oldest old patients, SLE may predominantly present with subacute cognitive and functional impairments.Low-dose treatment (prednisolone 7.5 mg/day and hydroxychloroquine 5 mg/kg/day) can reverse all SLE manifestations within 1 month.

Comparison of the disease activity score and the revised EUSTAR activity index in diffuse cutaneous systemic sclerosis patients.

OBJECTIVES: To compare the ability of the Disease Activity Score (DAS) and the Revised EUSTAR Activity Index (RAI) to detect diffuse cutaneous systemic sclerosis (dcSSc) patients requiring treatment intensification in a Belgian cohort. METHODS: We retrospectively compared the widely used DAS and the recently developed RAI in a longitudinal cohort (median follow-up of 42 months) of 62 dcSSc patients, of whom 30 with a disease duration ≤3 years at inclusion. Active disease was defined by a DAS ≥3/10 or a RAI ≥2.5/10. We chose a pragmatic definition to assess disease progression, namely any start or increase of glucocorticoids, immunosuppressants, anti-endothelin receptors or prostanoids. Sensitivity, specificity, negative and positive predictive values (NPV and PPV) of DAS and RAI for prediction of actual treatment changes were compared by ROC curves. RESULTS: According to RAI, 48% (of all dcSSc patients) and 55% (of ≤3 years dcSSc patients) were categorised as effectively active during follow-up while 34% and 43% according to DAS, respectively. The PPV and the NPV to detect disease progression, in ≤3 years dcSSc patients, were 59% and 89% for RAI vs 73% and 87% for DAS, respectively. The area under ROC curves were high for both scores (0.85 for RAI and 0.87 for DAS). CONCLUSIONS: Both scores are proven as predictive to detect disease activity, with a slightly better sensitivity for RAI. By contrast, RAI lacks specificity in predicting a real need for treatment intensification, thereby possibly leading to overtreatment.

Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis.

OBJECTIVES: In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. METHODS: Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3-26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. RESULTS: Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR < 1.0 g/g still had a high degree of histological activity (AI > 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8-178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies. CONCLUSION: Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.

Tapering of biological antirheumatic drugs in rheumatoid arthritis patients is achievable and cost-effective in daily clinical practice: data from the Brussels UCLouvain RA Cohort.

BACKGROUND/PURPOSE: Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings. RESULTS: Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost. CONCLUSION: In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts. TRIAL REGISTRATION: This retrospective non-interventional study was retrospectively registered with local ethics approval.

2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis.

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

Prediction of prognosis and renal outcome in lupus nephritis.

Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.