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

Abstract

ObjectivesThe 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.MethodsWe 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for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn.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.ResultsConcerning 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.ConclusionThis 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.

IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials

“…Despite the promising therapeutic implications, some drugs, including remtolumab, have been discontinued or are not active, underscoring the challenges and complexities associated with the development of IL-17-targeted therapies. The discontinuation of these drugs highlights the complexity of developing effective and safe IL-17 inhibitors and underscores the importance of continued research and refinement in this area ( 148 ).…”

Melittin promotes dexamethasone in the treatment of adjuvant rheumatoid arthritis in rats

“…Nonsteroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs (DMARDs; include conventional synthetic DMARDs, biological DMARDs and targeted synthetic DMARDs), and biological agents constitute the primary treatment options for RA. Glucocorticoids, extensively employed as first-line treatment drugs for various autoimmune and inflammatory diseases, are widely used in RA treatment ( Abbasi et al, 2018 ; Prasad et al, 2022 ; Denis et al, 2023 ). Dexamethasone (DEX), a pivotal glucocorticoid, significantly alleviates joint pain, stiffness, and swelling associated with RA, remaining a major drug in the market for RA treatment.…”