Biologika und „small molecules“ beim systemischen Lupus erythematodes

Biologicals and small molecules for systemic lupus erythematosus

Zusammenfassung

Gezielte Therapie ist ein rheumatologischer Traum, der mit den Biologika und zuletzt kleinen Molekülen für die rheumatoide Arthritis wahr geworden ist – und für den systemischen Lupus erythematodes (SLE) beginnt, wahr zu werden. Mit Belimumab steht das erste SLE-Biologikum jetzt auch subkutan zur Verfügung. In 4 unabhängigen Studien wurde der Endpunkt erreicht, und die langfristige Belimumab-Therapie hat die Organschädigung verlangsamt, ein zentrales Therapieziel. Die B‑Zell-Depletion mit Antikörpern gegen CD20 bleibt ein relevanter Ansatz, und die Kombination beider Ansätze ist eine spannende Idee. Die Blockade des Typ-I-Interferon-Rezeptors mit Anifrolumab weist eine positive Phase-3-Studie auf und mit Ustekinumab wird die Blockade von Interleukin-12 und -23 in Phase-3-Studien getestet. Auch die alten Ideen der TNF(Tumor-Nekrose-Faktor)- und Interleukin-6-Blockade sind noch nicht vom Tisch. Hinzu kommen die JAK(Januskinase)-Inhibition mit positiven Phase-2-Daten für Baricitinib und demnächst die Blockade von Bruton-Tyrosinkinase (BTK) sowie die Proteasominhibition. Die SLE-Therapie könnte also demnächst deutlich vielfältiger werden.

Abstract

Targeted treatment is a rheumatologist’s dream, which, with the advent of biologicals and more recently small molecules, has become true for rheumatoid arthritis and is about to translate into reality for systemic lupus erythematosus (SLE). Belimumab, the first biological approved for SLE, is now also available in a subcutaneous formulation. It is notable that this drug achieved the primary endpoint in four independent trials and demonstrated substantial reduction of organ damage accrual. The B cell depletion with antibodies against CD20 remains clinically relevant and of interest for future developments and the combination of both approaches (belimumab and anti-CD20) is an exciting idea. Blockade of the type I interferon receptor with anifrolumab was effective in a phase 3 trial and blocking interleukin-12 and interleukin-23 with ustekinumab is currently being tested in a phase 3 clinical trial. The old ideas of blocking tumor necrosis factor (TNF) and interleukin‑6 have also not yet been forgotten. More novel approaches comprise Janus kinase (Jak) inhibition with positive phase 2 data for baricitinib and soon inhibition of Bruton’s tyrosine kinase (BTK) as well as proteasome inhibitors. The treatment of SLE could therefore soon become much more varied.

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Correspondence to Prof. Dr. M. Aringer.

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M. Aringer gibt Advisory Boards und/oder Vorträge bei Astra-Zeneca, Lilly, GSK, MSD, Pfizer und Roche an. N. Leuchten und T. Dörner geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Aringer, M., Leuchten, N. & Dörner, T. Biologika und „small molecules“ beim systemischen Lupus erythematodes. Z Rheumatol 79, 232–240 (2020). https://doi.org/10.1007/s00393-020-00767-6

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Schlüsselwörter

  • Randomisierte klinische Prüfungen
  • B‑Zell-Depletion
  • Zytokinblockade
  • Januskinase-Hemmer
  • Targeted therapies

Keywords

  • Randomized clinical trials
  • B cell depletion
  • Cytokine blockade
  • Janus kinase inhibitors
  • Targeted therapies