A Phase II Trial of Lutikizumab, an Anti–Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Roy M. Fleischmann*, Henning Bliddal, Francisco J. Blanco, Thomas J. Schnitzer, Charles Peterfy, Su Chen, Li Wang, Sheng Feng, Philip G. Conaghan, Francis Berenbaum, Jean Pierre Pelletier, Johanne Martel-Pelletier, Ole Vaeterlein, Gurjit S. Kaeley, Wei Liu, Matthew P. Kosloski, Gwen Levy, Lanju Zhang, Jeroen K. Medema, Marc C. Levesque

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


Objective: To assess the efficacy and safety of the anti–interleukin-1α/β (anti–IL-1α/β) dual variable domain immunoglobulin lutikizumab (ABT-981) in patients with knee osteoarthritis (OA) and evidence of synovitis. Methods: Patients (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 receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI-assessed synovitis at week 26. Results: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab-treated and placebo-treated patients. Changes from baseline in MRI-assessed synovitis at week 26 and other key symptom- and most structure-related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high-sensitivity C-reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. Conclusion: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.

Original languageEnglish (US)
Pages (from-to)1056-1069
Number of pages14
JournalArthritis and Rheumatology
Issue number7
StatePublished - Jul 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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