Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis

Arthur Petitdemange; Julien Blaess; Jean Sibilia; Renaud Felten; Laurent Arnaud

doi:10.1177/1759720X20969261

Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis

Ther Adv Musculoskelet Dis. 2020 Dec 16:12:1759720X20969261. doi: 10.1177/1759720X20969261. eCollection 2020.

Authors

Arthur Petitdemange¹, Julien Blaess¹, Jean Sibilia¹, Renaud Felten¹, Laurent Arnaud²

Affiliations

¹ Department of Rheumatology, National Reference Center for Auto-Immune Diseases (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
² Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes et Systémiques Rares, Hôpital de Hautepierre, 1 Avenue Molière BP 83049, Strasbourg Cedex, 67098, France.

Abstract

Background: Pathogenic inflammatory pathways are largely shared between different autoimmune and inflammatory diseases (AIDs). This offers the potential to develop a given targeted therapy in several AIDs.

Methods: We analyzed two clinical trials registries (ClinicalTrials.gov and EU Clinical Trials Register) to identify the targeted therapies whose development is shared between at least two of the most common AIDs [rheumatoid arthritis (RA), spondyloarthritis (SpA), cutaneous psoriasis (cPso), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), giant cell arteritis (GCA), and multiple sclerosis (MS)] using an in-depth repurposing analysis.

Results: We identified 142 shared targeted therapies. The four diseases in which shared targeted therapies were the most numerous were RA (n = 92), cPso (n = 67), IBD (n = 58), and SLE (n = 56). The two clusters of diseases between which the overlap of targeted therapies was the most important were RA and SLE as well as RA, SpA, cPso, and IBD. The targeted therapies which were shared by five diseases or more were abatacept, ustekinumab, rituximab, anakinra, etanercept, infliximab, secukinumab, tofacitinib, alemtuzumab, tocilizumab, adalimumab, apremilast, baricitinib, belimumab, brodalumab, filgotinib, and upadacitinib. The most frequently targeted molecules and pathways were (by descending frequency): JAK-STAT pathways, Th17 axis, TNF-α, IL-6, costimulation molecules, BAFF, CD20, BTK, chemokines and integrins, IL-1, and type I interferon.

Conclusion: Many targeted therapies are developed in several AIDs, reflecting the overlap of pathogenic pathways and potential of drug repurposing. This suggests that a revision of the current, clinically based classification of AIDs towards a more mechanistic-based taxonomy might be relevant.

Keywords: autoimmune diseases; biological products; drug repositioning; investigational; molecular targeted therapy; therapies.