In:
Annals of the Rheumatic Diseases, BMJ, Vol. 78, No. 3 ( 2019-03), p. 413-420
Abstract:
To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA). Methods Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates. Results Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI –1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1α and IL-1β levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67). Conclusion Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2018-213336
DOI:
10.1136/annrheumdis-2018-213336.supp1
DOI:
10.1136/annrheumdis-2018-213336.supp2
DOI:
10.1136/annrheumdis-2018-213336.supp3
DOI:
10.1136/annrheumdis-2018-213336.supp4
DOI:
10.1136/annrheumdis-2018-213336.supp5
DOI:
10.1136/annrheumdis-2018-213336.supp6
DOI:
10.1136/annrheumdis-2018-213336.supp7
DOI:
10.1136/annrheumdis-2018-213336.supp8
DOI:
10.1136/annrheumdis-2018-213336.supp9
DOI:
10.1136/annrheumdis-2018-213336.supp10
DOI:
10.1136/annrheumdis-2018-213336.supp11
DOI:
10.1136/annrheumdis-2018-213336.supp12
Language:
English
Publisher:
BMJ
Publication Date:
2019
detail.hit.zdb_id:
1481557-6
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