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Dual Cytokine Inhibition Intriguing But May Not Work in PsA
November 14 2016 1:00 PM ET — via RheumReports
Dr. Philip Mease was the man of the hour at the SpA abstract session Sunday afternoon at ACR 2016, where he presented 3 studies. In the one summarized below, he collaborated with other powerhouse names in rheumatology including Dr. Genovese, Dr. Weinblatt and Dr. Peloso.
The trial was a phase 2 study of ABT-122, a TNF and IL-17-targeted dual variable domain immunoglobulin (DVD-Ig), in 240 PsA patients with inadequate MTX response. The premise sounds very promising. Since TNF and IL-17 inhibition separately are effective for skin and joints, maybe dual inhibition would be the home run we have been hoping for. Sadly, this molecule may be more of a strike out.
The trial design was of high quality: it was a RCT with patients randomized 3:3:3:1 to receive ABT-122 120mg or 240mg SC weekly, adalimumab 40mg q2weeks or matching placebo. The primary efficacy endpoint was ACR20 vs placebo at 12 weeks.
Results showed that both ABT-122 doses were superior to placebo on all efficacy outcomes. ACR 20 and PASI 90 for both doses were comparable to ADA. ACR50/70 scores and the PASI 75 were numerically higher with the higher dose of ABT-122 but the trend was not statistically significant.
The safety profile was acceptable with no serious infections observed. The authors concluded that although the infection rates were the same as a TNFi alone, the dual neutralization does not offer superior efficacy. It was not stated at the end of the presentation whether this is the end of the road for this drug or not. I do suspect, however, the search for a safe and effective dual inhibition molecule will continue.
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About the Author
Dr. Shelly Dunne
Dr. Shelley Dunne is a graduate of Memorial University of Newfoundland School of Medicine. She completed her training in Internal Medicine and a fellowship in Rheumatology at the University of Toronto. She has been in private practice since 1998 and is currently a consulting rheumatologist at the Toronto East General Hospital.
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