A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17
monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic
agents or had an inadequate response to tumor necrosis factor inhibitors.
Author(s): Genovese MC(1), Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie
L, Braun D, Berclaz PY, Banerjee S.
Affiliation(s): Author information:
(1)Stanford University, Palo Alto, California.
Publication date & source: 2014, Arthritis Rheumatol. , 66(7):1693-704
OBJECTIVE: To evaluate ixekizumab, an anti-interleukin-17A (anti-IL-17A)
monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients:
biologics-naive patients and patients with an inadequate response to tumor
necrosis factor (TNF) inhibitors.
METHODS: In this phase II, randomized, double-blind study, placebo or ixekizumab
was administered subcutaneously to 260 biologics-naive patients and 188 patients
with an inadequate response to TNF inhibitors at weeks 0, 1, 2, 4, 6, 8, and 10
with concomitant disease-modifying antirheumatic drugs. The primary objective was
to determine the dose-response relationship of ixekizumab as measured by the
proportion of biologics-naive patients meeting the American College of
Rheumatology 20% improvement criteria (ACR20) at week 12.
RESULTS: Using a logistic regression model defined a priori, a statistically
significant dose-response relationship as measured by ACR20 response rates at
week 12 was detected in biologics-naive patients (P = 0.031). For patients with
an inadequate response to TNF inhibitors, ACR20 responses at week 12 were
significantly better with ixekizumab than placebo (P < 0.05). Decreases in the
Disease Activity Score in 28 joints using the C-reactive protein level
(DAS28-CRP), Clinical Disease Activity Index (CDAI), and CRP level from baseline
were observed at week 12 in the ixekizumab groups in both populations (P < 0.05
versus placebo). Onset of action was rapid in some dose groups in both
populations, with improvements in the ACR20, DAS28-CRP, CRP levels, and CDAI
observed by day 3 (P < 0.05). Adverse events occurred with similar frequencies
overall in the ixekizumab and placebo groups. Infections were more frequent with
ixekizumab than placebo (biologics-naive 25% versus 19%; inadequate responders to
TNF inhibitors 27% versus 25%). No mycobacterial or invasive fungal infections
were reported.
CONCLUSION: Ixekizumab improved RA signs and symptoms in RA patients who were
either naive to biologics treatment or had an inadequate response to TNF
inhibitors. The safety profile was similar to that of other biologic agents, with
no unexpected safety concerns.
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