Sunday, June 29, 2014

ABT-122 at the EULAR 2014 Meeting in Paris

ABT-122 is an anti-TNF/IL-17 Dual Variable Domain immunoglobulin (DVD-Ig). It had been "demonstrated that dual neutralization of TNF and IL-17 provides greater efficacy than blocking either cytokine alone in mouse collagen induced arthritis".
Allow me to voice my skepticism already at this point. M. Genovese and colleagues have presented a study two years ago, in which secukinumab (an anti-IL-17a MAB) has been studied in patients with rheumatoid arthritis still active despite methotrexate therapy. “Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16.” This endpoint hadn’t been achieved. I'm not convinced that IL-17-inhibition is working in rheumatoid arthritis, but let's come to the study, which has been presented in  Paris.

C. Cuff and colleagues presented this study: "DUAL NEUTRALIZATION OF TNF AND IL-17 WITH A DVD-IG PROTEIN IS EFFICACIOUS IN COLLAGEN INDUCED ARTHRITIS". A mouse study! Conclusions: "These data demonstrate that dual blockade of TNF and IL-17 with a DVD-Ig molecule is efficacious in a pre-clinical model of arthritis and support the rationale to clinically evaluate the anti-human TNF/IL-17 DVD-Ig protein, ABT-122, in rheumatoid arthritis and other inflammatory disorders."

I would expect a benefit in " other inflammatory disorders" like psoriatic arthritis or anylosing spondylitis. But ... I have my reservations. Blocking two cytokines at the same time has been avoided so far. All combinations look at a biologic DMARD (boDMARD) and a conventional/chemical DMARD (csDMARD) and not two biologics. The fear is high that one induces more side effects. Even if further studies prove, that ABT-122 isn't working in rheumatoid arthritis, it might open Pandora's box to study combinations of two biologic DMARDs.


No comments:

Post a Comment