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

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Bispebjerg Hospital - en del af Københavns Universitetshospital

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Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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, J-P, Martel-Pelletier, J, Vaeterlein, O, Kaeley, GS, Liu, W, Kosloski, MP, Levy, G, Zhang, L, Medema, JK & Levesque, MC 2019, 'A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis' Arthritis & rheumatology, bind 71, nr. 7, s. 1056-1069. https://doi.org/10.1002/art.40840

APA

Fleischmann, R. M., Bliddal, H., Blanco, F. J., Schnitzer, T. J., Peterfy, C., Chen, S., ... Levesque, M. C. (2019). A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & rheumatology, 71(7), 1056-1069. https://doi.org/10.1002/art.40840

CBE

Fleischmann RM, Bliddal H, Blanco FJ, Schnitzer TJ, Peterfy C, Chen S, Wang L, Feng S, Conaghan PG, Berenbaum F, Pelletier J-P, Martel-Pelletier J, Vaeterlein O, Kaeley GS, Liu W, Kosloski MP, Levy G, Zhang L, Medema JK, Levesque MC. 2019. A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & rheumatology. 71(7):1056-1069. https://doi.org/10.1002/art.40840

MLA

Fleischmann, Roy M o.a.. "A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis". Arthritis & rheumatology. 2019, 71(7). 1056-1069. https://doi.org/10.1002/art.40840

Vancouver

Fleischmann RM, Bliddal H, Blanco FJ, Schnitzer TJ, Peterfy C, Chen S o.a. A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & rheumatology. 2019 jul;71(7):1056-1069. https://doi.org/10.1002/art.40840

Author

Fleischmann, Roy M ; Bliddal, Henning ; Blanco, Francisco J ; Schnitzer, Thomas J ; Peterfy, Charles ; Chen, Su ; Wang, Li ; Feng, Sheng ; Conaghan, Philip G ; Berenbaum, Francis ; Pelletier, Jean-Pierre ; Martel-Pelletier, Johanne ; Vaeterlein, Ole ; Kaeley, Gurjit S ; Liu, Wei ; Kosloski, Matthew P ; Levy, Gwen ; Zhang, Lanju ; Medema, Jeroen K ; Levesque, Marc C. / A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. I: Arthritis & rheumatology. 2019 ; Bind 71, Nr. 7. s. 1056-1069.

Bibtex

@article{43fe54f3d77b480c8affa7d743103bf4,

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

abstract = "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.",

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

note = "{\circledC} 2019, American College of Rheumatology.",

year = "2019",

month = "7",

doi = "10.1002/art.40840",

language = "English",

volume = "71",

pages = "1056--1069",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "John Wiley and Sons Ltd",

number = "7",

}

RIS

TY - JOUR

T1 - A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

AU - Fleischmann, Roy M

AU - Bliddal, Henning

AU - Blanco, Francisco J

AU - Schnitzer, Thomas J

AU - Peterfy, Charles

AU - Chen, Su

AU - Wang, Li

AU - Feng, Sheng

AU - Conaghan, Philip G

AU - Berenbaum, Francis

AU - Pelletier, Jean-Pierre

AU - Martel-Pelletier, Johanne

AU - Vaeterlein, Ole

AU - Kaeley, Gurjit S

AU - Liu, Wei

AU - Kosloski, Matthew P

AU - Levy, Gwen

AU - Zhang, Lanju

AU - Medema, Jeroen K

AU - Levesque, Marc C

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

U2 - 10.1002/art.40840

DO - 10.1002/art.40840

M3 - Journal article

VL - 71

SP - 1056

EP - 1069

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 7

ER -

ID: 57854920