Novel rheumatoid arthritis treatments

3 minute read

The latest results for dual JAK1/TYK2 inhibitor TLL-018, which created quite a stir at EULAR, had the audience buzzing.

While we are fortunate to have targeted therapies, we still fail to achieve remission or low disease activity in a significant number of patients who present to our clinics.

The novel RA treatment session at ACR Convergence 2023 reported on two potential therapies trying to address this.

Efficacy and safety of nipocalimab in patients with moderate to severe active RA

Presented by Peter Taylor of the University of Oxford, this study focuses on nipocalimab, designed to lower pathogenic IgG levels, including ACPAs, by blocking the neonatal Fc receptor.

In the IRIS-RA trial, 53 patients showed a non-significant trend towards efficacy in the nipocalimab group, with a mean change in DAS28-CRP score of –1.17 versus –0.62 in the placebo group. While numerical improvements across ACR20, ACR50, ACR70, and ACR90 criteria were good to see, the small sample size and preliminary nature of the results call for cautious interpretation.

The safety profile was notable, with 81% experiencing TEAEs compared to placebo’s 60%, including serious events like an infusion-related reaction and deep-vein thrombosis.

TLL-018 goes head-to-head with tofacitinib in patients with active RA

We were excited by the preliminary results when they were unveiled at EULAR earlier this year, so the final results for this study comparing TLL-018, a dual JAK1/TYK2 inhibitor, with tofacitinib were eagerly anticipated.

Results are good, really good.

The study enrolled 101 RA patients with inadequate response or intolerance to methotrexate.

At week 12, ACR50 response rates were markedly higher in the TLL-018 treated groups: 48%, 65%, and 72% for the 10mg, 20mg, and 30mg doses, respectively, compared to 41% for tofacitinib. The 20mg and 30mg doses of TLL-018 were statistically superior to tofacitinib (p<0.05).

The clinical remission (DAS28-CRP<2.6) data at week 12 was very impressive with 39%, 37%, 57% and 17% for the 10, 20, 30mg TLL-018 and tofacitinib, respectively.

TLL-018’s dual inhibition approach is hypothesised to enhance RA treatment efficacy.

The safety profile was manageable, with hyperlipidaemia and respiratory infections being the most common AEs. Notably, the 20mg TLL-018 group reported two cases of herpes zoster, while the tofacitinib group had one case of malignancy. There was absence of venous thromboembolism or major adverse cardiovascular events.

Concluding reflections

While the IRIS-RA trial offers a glimpse into a potential new pathway for treatment, its small scale and preliminary nature call for cautious optimism.

In contrast, TLL-018’s results against tofacitinib were compelling. This seems a potent molecule with good safety. We are looking forward to the phase 3 trials, given this might offer us a new avenue for our “difficult-to-treat” RA patients.

  • 0839: Efficacy and safety of nipocalimab in patients with moderate to severe active rheumatoid arthritis
  • 0840: Head-to-head comparison of TLL-018 and tofacitinib in patients with active rheumatoid arthritis: Final results from a phase IIa study

Dr Irwin Lim is the editor of Rheumatology Republic. He is a Sydney-based rheumatologist and director of BJC Health.

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