A Phase 2 Trial of Lutikizumab, an Anti-Interleukin 1alpha/beta Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Arthritis & Rheumatology
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Fleischmann RM, Bliddal H, Blanco FJ, Schnitzer TJ, Peterfy C, Chen S, Wang L, Feng S, Conaghan PG, Berenbaum F, Pelletier JP, Martel-Pelletier J, Vaeterlein O, Kaeley GS, Liu W, Kosloski MP, Levy G, Zhang L, Medema JK and Levesque MC.

Arthritis Rheumatol. 2019 Jan 17.

DOI: 10.1002/art.40840

Abstract

OBJECTIVE:

To assess the efficacy and safety of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in subjects with knee osteoarthritis (OA) and evidence of synovitis.

METHODS:

Subjects (N=350; 347 analyzed) with Kellgren-Lawrence grade 2-3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to placebo or lutikizumab 25, 100 or 200 mg subcutaneously every 2 weeks for 50 weeks. The co-primary endpoints were change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain index at week 16 and change from baseline in MRI synovitis at week 26.

RESULTS:

WOMAC pain at week 16 improved significantly versus placebo with lutikizumab 100 mg (P=0.050) but not 25 or 200 mg. Beyond week 16, WOMAC pain was reduced in all groups but was not significantly different for lutikizumab and placebo. Changes from baseline in MRI synovitis at week 26 and other key symptom- and most structure-related endpoints at weeks 26 and 52 were not significantly different for lutikizumab and placebo. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumabversus placebo. Neutrophil and high-sensitivity C-reactive protein reductions plateaued at lutikizumab 100 mg. Immunogenicity to lutikizumabdid not meaningfully affect systemic lutikizumab concentrations.

CONCLUSION:

The limited improvement of WOMAC pain and the lack of synovitis improvement with lutikizumab, together with published trialresults for other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/anti-inflammatory therapy in most patients with kneeOA and associated synovitis.