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Journal Article
Review
[Biologics for connective tissue diseases and vasculitides].
Der Internist 2022 Februrary
Despite therapy with glucocorticoids (GC) and conventional immunosuppressants, patients with connective tissue diseases and vasculitides often develop functionally relevant and prognostically unfavourable internal organ damage. Based on new pathogenetic insights, biologics and small molecules have recently been studied as targeted therapies for collagen vascular diseases and vasculitides. The B lymphocyte stimulator antagonist belimumab has been used for the treatment of systemic lupus erythematosus (SLE) for several years and has recently also been approved as an add-on therapy for lupus nephritis. Anifrolumab, an antibody against the type‑1 interferon receptor, has also been shown to be effective in phase III trials for the treatment of SLE. The interleukin (IL)-6-antagonist tocilizumab showed efficacy in the treatment of interstitial lung disease (ILD) in systemic sclerosis (SSc) and thus has been approved in the USA, although the phase III trial had a negative primary endpoint. In Europe the tyrosine inhibitor nintedanib is approved for progressive ILD in SSc. Tocilizumab is approved for the treatment of giant cell arteritis and reduces both the risk of recurrence and the cumulative GC requirement. The B‑lymphocyte depleting antibody rituximab is approved for induction and maintenance therapy of granulomatosis with polyangiitis and microscopic polyangiitis (MPA) and is currently also being investigated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). In patients with EGPA, the IL‑5 antibody mepolizumab leads to improved disease control and reduces GC requirements. A phase III trial of the small molecule antagonist avacopan targeting the complement C5a receptor as a replacement for high-dose GC in induction therapy of GPA and MPA met its primary endpoints. Various other biologics and small molecule antagonists are currently in clinical development for several type of vasculitis and collagen vascular diseases, some of them at advanced stages.
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