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.
[THU0521]
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.
Links:
Secukinumab at the EULAR 2012 Meeting: http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html
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