The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials

Abstract

Objectives: The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in the coming years.

Methods: We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn. The search was performed on February 2023 with the keywords "spondyloarthritis", "ankylosing spondylitis" and "psoriatic arthritis". For each molecule, we only considered the study at the most advanced stage of clinical development.

Results: Concerning axial SpA (axSpA), a total of 44 DMARDs were identified: 6 conventional synthetic DMARDs (csDMARDs), 27 biological DMARDs (bDMARDs) and 11 targeted synthetic DMARDs (tsDMARDs). Among the 18 targeted treatments (b+tsDMARDs) in current development, corresponding trials reached phase I (n=1), II (n=10) and III (n=7). Ten molecules are IL-17 inhibitors, two Janus kinase (JAK) inhibitors and two granulocyte-macrophage colony-stimulating factor inhibitors; four have another mode of action. Concerning psoriatic arthritis (PsA), 44 DMARDs were identified: 5 csDMARDs, 27 bDMARDs and 12 tsDMARDs. Among the 15 molecules in current development, corresponding trials reached phase II (n=8) and III (n=7). Six molecules are JAK inhibitors, six IL-17 inhibitors and one an IL-23 inhibitor; two have another mode of action.

Conclusion: This systematic review identified 18 and 15 molecules in clinical development for axSpA and PsA, respectively, which suggests a strengthening of the therapeutic arsenal in the coming years. However, with so many DMARDs but low target diversity, we will need to develop strategies or biomarkers to help clinicians make informed treatment decisions.

Keywords: ankylosing spondylitis; psoriatic arthritis; spondyloarthritis; therapeutics.

Figure 1

Study flow chart. bDMARDs, biologic al disease-modifying anti-rheumatic drugs; csDMARD, conventional synthetic DMARD; NSAID, non-steroidal anti-inflammatory drug; tsDMARDs, targeted synthetic DMARD.

Figure 2

Currently marketed and in-development disease-modifying antirheumatic drugs (DMARDs), their mechanisms of action and development phase. (A) Venn diagram of marketed and in development DMARDs and their development phase in axial spondyloarthritis, psoriatic arthritis or both. (B) Axial spondyloarthritis DMARDs according to their mechanism of action, phases of development and status. (C) Psoriatic arthritis DMARDs according to their mechanism of action, phases of development and status. bDMARDs, biological DMARD; csDMARD, conventional synthetic DMARD; PsA, psoriatic arthritis; tsDMARD, targeted synthetic DMARD.