Camels and psoriatic arthritis - a new treatment link Save

I am a big fan of animals and wildlife. Whenever I can, I try to wander outdoors to look for our friends big and small in the animal kingdom. If it rains, as often it does in the UK, the latest edition of Planet Earth will do. So, I was naturally attracted to the presentation by Professor Iain McInnes from the University of Glasgow, oral presentation OP0195 at #EULAR2024 where the link between camels and psoriatic arthritis was made.

Nanobodies are single domain antibodies derived from the Camelidae family of mammals which include camels, llamas and alpacas. They are composed of two identical heavy chains and lack a light chain. They are lighter ~ 40kDa compared to conventional antibodies which are ~150 kDa.

Sonelikomab is a humanised nano body that selectively binds with high affinity to both IL-17A and IL-17F. The ARGO study is a 24 week prospective double blind placebo controlled Phase 2 trial. Mean duration of PsA 5.4 years, and 17% had prior biologic use.

There were  5 arms to the study. Participants with active PsA were randomised (1:1:1:1:1)

• sonelokimab 120 mg Q4W (with induction),
• sonelokimab 60 mg Q4W (with induction)
• sonelokimab 60 mg Q4W (no induction [NI]),
• placebo
• adalimumab (ADA) 40 mg Q2W (reference arm, not powered for statistical comparison)

At 12 weeks, there were 207 patients randomised. The study achieved its primary endpoint with a significantly greater proportion of patients treated with sonelokimab achieved the ACR50 vs. placebo. Significant clinical responses across domains were observed by week 4.

The secondary outcomes were also achieved with >40% of patients in the sonelokimab 60 mg arm achieved MDA composite, >30% in the sonelokimab 120 and 60 mg arms achieved a composite of both ACR 50 and PASI 100, and >25% in the sonelokimab 60 mg arm achieved a

composite of both ACR 70 and PASI 100.

Achievement of higher treatment response thresholds was reflected by improvements in patient QoL, including Psoriatic Arthritis Impact of Disease (PsAID)-12.

Sonelokimab was well tolerated with no unexpected safety findings; there were no cases of IBD or MACE and two (1.6%) mild or moderate cases of oral candidiasis. The discontinuation rate was <4%.

This Phase 2 study showed that IL-17A- and IL-17F-inhibiting Nanobody sonelokimab delivers rapid onset and effective clinical response, including high-threshold outcomes, such as MDA, ACR70 and PASI100 compared with placebo in patients with active PsA, with a favorable benefit–risk profile.

There are a few important points to consider. Firstly, these data support further exploration of the role for Nanobody-mediated inhibition of pivotal cytokine pathways in PsA. Secondly, it allows for comparisons with other IL-17A/F inhibitors and if the difference with nanobody-mediated inhibition with tighter binding translates to any clinical change.