Psoriatic arthritis - Emerging treatments

Bimekizumab

Bimekizumab, an interleukin (IL) inhibitor monoclonal antibody targeting both IL-17A and IL-17F, is approved by the European Medicines Agency (EMA), alone or in combination with methotrexate, for adults with active psoriatic arthritis (PsA) who have had an inadequate response or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs). A phase 2 clinical trial demonstrated that bimekizumab significantly improved ACR50 at 12 weeks compared with placebo in patients with PsA, with an acceptable adverse effect profile.[97] Response rates were maintained in a high proportion of patients across both skin and joint outcomes at 60 weeks.[98] An open-label extension trial reported that patients sustained joint and skin improvements at 3 years with no new safety issues.[99]

Brodalumab

Brodalumab, an IL-17A inhibitor monoclonal antibody, is approved for moderate-to-severe plaque psoriasis in the US. It carries a warning for the risk of suicidal ideation. However, a 2-year US pharmacovigilance report of 2677 patients taking brodalumab found that no suicide attempts or completed suicides were reported, and 25 reports of depression were recorded.[100] Brodalumab had demonstrated rapid and significant improvements in PsA signs and symptoms in two phase 3 clinical trials, with improvements across articular, enthesitis, dactylitis, and skin domains compared with placebo.[101] The trials were terminated early due to an observed increase in suicidal ideation and behavior in the brodalumab arm. A protocol amendment allowed patients with a prior history of suicidal ideation and behavior to be excluded from the trials, and an analysis of the rates of depression and suicidal ideation and behavior in patients without a prior history were found to be similar for both brodalumab- and placebo-treated patients. The safety profile was otherwise found to be consistent with other IL-17 inhibitors.[101]

Deucravacitinib

Deucravacitinib, an oral tyrosine kinase 2 inhibitor, is approved by the Food and Drug Administration (FDA) and the EMA for the treatment of psoriasis. It has demonstrated improved symptomatic responses for patients with PsA compared with placebo over 16 weeks in a phase 2 clinical trial.[102] No serious adverse effects were reported; however, tyrosine kinase 2 is part of the Janus kinase family and more data are needed.

Brepocitinib

Brepocitinib, an investigational tyrosine kinase 2/Janus kinase 1 dual inhibitor, has demonstrated its efficacy at reducing the symptoms of PsA in patients with moderately to severely active PsA compared with placebo in a phase 2b trial.[103]

Chimeric antigen receptor-T (CAR-T) cell therapy

CAR-T cell therapy is of interest in autoimmune diseases, as it theoretically allows for the specific targeting and deletion of pathologically activated immune cells.[104] Preclinical studies have been carried out in in vitro and in vivo models of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis.[104]

Combination therapies

Combination immunomodulatory treatment may show promise for enhancing musculoskeletal response rates for patients with PsA. Researchers are looking to oncology and other chronic inflammatory diseases for insights on selecting and ordering synergistic agents to work across diverse pathologic pathways in patients with refractory disease.[105]