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From sequential to combination and personalised therapy in lupus nephritis: moving towards a paradigm shift?
  1. Ioannis Parodis1,2,3,
  2. Frederic A Houssiau4,5
  1. 1 Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2 Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  3. 3 Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  4. 4 Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
  5. 5 Rheumatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  1. Correspondence to Professor Frederic A Houssiau, Pôle de Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium; frederic.houssiau{at}


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.

  • lupus nephritis
  • lupus erythematosus
  • systemic
  • biological therapy
  • therapeutics
  • B-lymphocytes

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  • Handling editor Josef S Smolen

  • Contributors IP and FAH conceived of and drafted the manuscript, revised it critically for important intellectual content, and approved the final version prior to submission.

  • Funding IP is supported by the Swedish Rheumatism Association (R-932236), King Gustaf V’s 80-year Foundation (FAI-2019-0635), Professor Nanna Svartz Foundation (2019-00290), Ulla and Roland Gustafsson Foundation (2019-12), Region Stockholm and Karolinska Institutet. FAH is supported by Fondation Saint-Luc and Fonds National de la Recherche Scientifique.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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