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

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.

Figure 1.

Associations of diseases based on the number of shared targeted therapies. For each disease, a Venn diagram shows three closely related diseases based on the number of shared targeted therapies. (A) For RA (also valid for SLE). (B) For SpA (also valid for cPso and IBD). (C) For pSS. (D) For SSc. (E) For IIM. (F) For GCA. (G) For MS. Numbers in parentheses represent the number of trials. cPso, cutaneous psoriasis; GCA, giant cell arteritis; IBD, inflammatory bowel diseases; IIM, idiopathic inflammatory myopathies; MS, multiple sclerosis; pSS, primary Sjögren’s syndrome; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SpA, spondyloarthritis; SSc, systemic sclerosis.

Figure 2.

Number of shared targeted therapies developed in each disease and in the different sets of diseases. The horizontal bars on the left of the figure represent, for each disease, the number of molecules in development shared with one or more of the other diseases. The points connected by lines at the bottom of the figure show all the sets of diseases for which shared drugs exist. Finally, the vertical bars represent the number of molecules shared by each set of disease. cPso, cutaneous psoriasis; GCA, giant cell arteritis; IBD, inflammatory bowel diseases; IIM, idiopathic inflammatory myopathies; MS, multiple sclerosis; PMR, polymyalgia rheumatica; pSS, primary Sjögren’s syndrome; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SpA, spondyloarthritis; SSc, systemic sclerosis; TA, Takayasu arteritis.