Pharmacokinetics and Tolerability of a Dual Variable Domain Immunoglobulin ABT-981 Against IL-1α and IL-1β in Healthy Subjects and Patients With Osteoarthritis of the Knee

Abstract Background The assessment of improvement or maintenance of joint health in healthy subjects is a great challenge. The aim of the study was the evaluation of a joint stress test to assess joint discomfort in subjects with activity-related knee joint discomfort (ArJD). Results Forty-five subjects were recruited to perform the single-leg-step-down (SLSD) test (15 subjects per group). Subjects with ArJD of the knee (age 22–62 years) were compared to healthy subjects (age 24–59 years) with no knee joint discomfort during daily life sporting activity and to subjects with mild-to-moderate osteoarthritis of the knee joint (OA, Kellgren score 2–3, age 42–64 years). The subjects performed the SLSD test with two different protocols: (I) standardization for knee joint discomfort; (II) standardization for load on the knee joint. In addition, range of motion (ROM), reach test, acute pain at rest and after a single-leg squat and knee injury, and osteoarthritis outcome score (KOOS) were assessed. In OA and ArJD subjects, knee joint discomfort could be reproducibly induced in a short time interval of less than 10 min (200 steps). In healthy subjects, no pain was recorded. A clear differentiation between study groups was observed with the SLSD test (maximal step number) as well as KOOS questionnaire, ROM, and reach test. In addition, a moderate to good intra-class correlation was shown for the investigated outcomes. Conclusions These results suggest the SLSD test is a reliable tool for the assessment of knee joint health function in ArJD and OA subjects to study the improvements in their activities. Further, this model can be used as a stress model in intervention studies to study the impact of stress on knee joint health function.

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Chapter 5: Lessons Learned in Understanding Dual Variable Domain-Ig (DVD-Ig) Structural Complexity to Select DVD-Ig Lead and Therapeutic Candidates

Development of Biopharmaceutical Drug-Device Products - AAPS Advances in the Pharmaceutical Sciences Series ◽

10.1007/978-3-030-31415-6_5 ◽

2020 ◽

pp. 91-115

Author(s):

W. Blaine Stine ◽

Dana I. Filoti ◽

Tariq Ghayur

Keyword(s):

Structural Complexity ◽

Lessons Learned ◽

Variable Domain ◽

Dual Variable

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Identification of Anti-ErbB2 Dual Variable Domain Immunoglobulin (DVD-Ig™) Proteins with Unique Activities

PLoS ONE ◽

10.1371/journal.pone.0097292 ◽

2014 ◽

Vol 9 (5) ◽

pp. e97292 ◽

Cited By ~ 9

Author(s):

Jinming Gu ◽

Jinsong Yang ◽

Qing Chang ◽

Xiaoqing Lu ◽

Jieyi Wang ◽

...

Keyword(s):

Variable Domain ◽

Dual Variable

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Is Lutikizumab, an Anti–Interleukin-1α/β Dual Variable Domain Immunoglobulin, efficacious for Osteoarthritis? Results from a bayesian network meta-analysis

BioMed Research International ◽

10.1155/2020/9013283 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Ziqin Cao ◽

Yajia Li ◽

Wanchun Wang ◽

Shuo Jie ◽

Xuantao Hu ◽

...

Keyword(s):

Pain Relief ◽

Bayesian Network ◽

Meta Analysis ◽

Variable Domain ◽

Dual Variable ◽

Efficacy And Safety ◽

Study Results ◽

Interleukin 1Α ◽

Cox 2 ◽

Cox 2 Inhibitors

Objective. Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. Methods. We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. Results. 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. Conclusions. Lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study.

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