Emerging Therapies in Spondyloarthritis: A Promising Pipeline Save

Growing awareness of spondyloarthropathies over the last two decades has inevitably led to a better understanding of the pathophysiology of spondyloarthritis (SpA), and subsequently increased interest in more distinct, disease state specific treatment options. An abstract session (6S408) satisfies curiosity of many in search of  promising emerging therapies for this disease state.

Amongst some of the emergent treatments covered, Brepocitinib, a tyrosine kinase 2/Janus kinase 1 inhibitor, was shown to be superior to placebo in numerous disease domains in a phase 2b PBO controlled trial (abstract #0488). In this particular study, significant numbers of patients achieved high ACR20/50/70 scores, Minimal Disease Activity, and Psoriasis Activity and Severity Index 75/90 by week 16 and maintained their response to week 52. In terms of adverse events (AEs), most were mild; but there were 17 serious AEs (predominantly infectious complications, 2 cases of malignancy). There were no major adverse cardiovascular events, venous thromboembolic events, or deaths.

Promising results from an interesting phase 1 trial, targeting a new mechanism, were reported by Dr. Mensah (abstract #0489) . In this trial, multiple doses of CC-99677 were given to healthy adults and led to sustained reduction of ex vivo whole blood TNF-α, IL-6, and chemokine synthesis. The drug was well tolerated and the findings support further phase 2 trials of CC-99677 inhibition of MK2 in patients with spondyloarthritis.

Abstract #0490 provides insight on the effect TYK 2 inhibitor, deucravacitinib, on biomarkers and disease activity in Psoriatic arthritis (PsA). In this phase II trial, PsA patients who received deucravacitinib experienced reduction in  IL-23/IL-17 and IFN-I levels. Decreases in MMP3 and  the neoepitope marker of Type IV collagen degradation mediated by MMPs (C4M) and improved disease activity scores were superior to placebo. Lastly, deucravacitinib treatment resulted in no clinically meaningful changes in mean levels of serum cholesterol, creatinine, neutrophils, and platelets over time, hinting on potentially favorable side effect profile.

The final abstract (#0491) in this group, was an update of the ongoing phase 2B study of dual interleukin (IL)-17F and IL-17A inhibitors, Bimekizumab (BKZ), in Ankylosing Spondylitis (AS). In this study Dr. Gensler reports sustained efficacy and no new safety signals after 3 years of treatment. In particular, initial improvements ASDAS-CRP (3.9 to 2.1) and BASDAI total score (6.5 to 3.0) at 48 weeks were later sustained after 2 years of BKZ treatment.

Overall safety with the open label extension study of BKZ did not raise any additional concerns regarding exposure-adjusted incidence rates of TEAEs. Candida infections which a typically a concern with this MOA were mild or moderate. AEs of inflammatory bowel disease, anterior uveitis, and injection site reactions were low.

In summary, some new and interesting mechanisms of action are on the horizon and hopefully bring hope and relief for those who suffer greatly from spondyloarthritis.