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[Discussion about the presentation: « What is new in lupus nephritis?»]

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.

La norme de soins actuelle de la néphrite lupique (LN) est basée sur un traitement immunosuppresseur séquentiel destiné à induire une réponse (traitement d’induction) et à éviter les récidives (traitement d’entretien). Force est de constater que les résultats de cette approche sont loin d’être satisfaisants, avec seulement 20–30 % de réponse rénale complète à 6–12 mois, au moins 20 % de patients souffrant d’insuffisance rénale chronique et 5–20 % d’insuffisance rénale terminale 10 ans après le diagnostic. Nous discutons notamment de deux nouveaux traitements, la voclosporine et le belimumab, récemment enregistrés par les agences des médicaments suite à d’essais contrôlés qui ont démontré leur supériorité en ajout d’un traitement immunosuppresseur standard. D’autres traitements combinés, avec de l’obinutuzumab ou de l’anifrolumab sont actuellement testés en Phase III. Il fait peu de doute que le paradigme thérapeutique évolue vers des combinaisons. L’étape suivante consistera à choisir avec discernement la plus appropriée chez un patient donné. Il est probable que la réponse viendra de l’analyse de biomarqueurs, en particulier étudiés sur les biopsies rénales elles-mêmes (initiales et répétées), permettant de développer une médecine de précision. L’horizon semble enfin se dégager pour les patients souffrant de NL., [What is new in lupus nephritis?] The current standard of care in lupus nephritis (LN) consists of an initial immunosuppressive regimen therapy aimed at inducing a response and a subsequent maintenance phase to prevent recurrence. 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. 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 LN 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. Undoubtedly, the treatment landscape in LN is changing, with combination treatment regimens challenging the sequential concept. Meanwhile, the enrichment of the treatment armamentarium shifts the need from new efficient therapies to the challenge of how to select the right treatment for the right patient. This has to be addressed by biomarker surveys along with initial and repeated tissue-level mapping of inflammatory phenotypes, which will ultimately lead to precision medicine therapeutic approaches. After many years of trial failures, we may now anticipate a heartening future for patients with LN.

The current standard of care for lupus nephritis has so far been based on sequential immunosuppressive therapy aimed to induce a response, called induction therapy, and to prevent relapse, called maintenance therapy. The results of this approach are deemed unsatisfactory, with only 20-30% of complete renal responses observed at 6-12 months, with at least 20% of patients suffering from chronic kidney failure and 5-20% from end-stage kidney disease at 10 years post-diagnosis. Herein, we have briefly discussed two new treatments, consisting of belimumab and voclosporin, recently registered by drug agencies in the aftermath of controlled trials that demonstrated their superiority given in addition to standard immunosuppressive therapy. Further progress in rheumatoid arthritis is being based on further integrating goals, such as monitoring patients' daily symptoms and well managing comorbidities like cardiovascular disease. An improved understanding of its pathophysiology has enabled translational research designed to develop new therapeutic strategies including numerous targeted biological and synthetic agents. Voici quelques nouveautés importantes dans le domaine de la rhumatologie au cours de l’année 2021. La norme de soins actuelle de la néphrite lupique est basée sur un traitement immunosuppresseur séquentiel destiné à induire une réponse (traitement d’induction) et à éviter les récidives (traitement d’entretien). Les résultats de cette approche ne sont pas suffisamment satisfaisants, avec seulement 20 - 30% de réponse rénale complète à 6 -12 mois, au moins 20% de patients souffrant d’insuffisance rénale chronique et 5 -20% d’insuffisance rénale terminale 10 ans après le diagnostic. Nous discutons brièvement de deux nouveaux traitements, le belimumab et la voclosporine, récemment enregistrés par les agences de médicaments suite à des essais contrôlés qui ont démontré leur supériorité en ajout d’un traitement immunosuppresseur standard. Les progrès engendrés dans le

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.

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.

The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were rated, using a 0 (strongly disagree) to 10 (strongly agree) numerical rating scale. Statements with agreement of 75% or greater were selected and further validated by the expert panel. Consensus was reached on 27 statements, grouped in 14 recommendations, for the use of the PGA in SLE, design of the PGA scale, practical considerations for PGA scoring, and the relationship between PGA values and levels of disease activity. Among these recommendations, the expert panel agreed that the PGA should consist of a 0–3 visual analogue scale for measuring disease activity in patients with SLE in the preceding month. The PGA is intended to rate the overall disease activity, taking into account the severity of active manifestations and clinical laboratory results, but excluding organ damage, serology, and subjective findings unrelated to disease activity. The PGA scale ranges from “no disease activity” (0) to the “most severe disease activity” (3) and incorporates the values 1 and 2 as inner markers to categorise disease activity as mild (≥0·5 to 1), moderate (>1 and ≤2) and severe (>2 to 3). Only experienced physicians can rate the PGA, and it should be preferably scored by the same rater at each visit. The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials.