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Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study

OBJECTIVE: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results....

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Autores principales: Eckstein, Felix, Hochberg, Marc C, Guehring, Hans, Moreau, Flavie, Ona, Victor, Bihlet, Asger Reinstrup, Byrjalsen, Inger, Andersen, Jeppe Ragnar, Daelken, Benjamin, Guenther, Oliver, Ladel, Christoph, Michaelis, Martin, Conaghan, Philip G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292562/
https://www.ncbi.nlm.nih.gov/pubmed/33962962
http://dx.doi.org/10.1136/annrheumdis-2020-219181
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author Eckstein, Felix
Hochberg, Marc C
Guehring, Hans
Moreau, Flavie
Ona, Victor
Bihlet, Asger Reinstrup
Byrjalsen, Inger
Andersen, Jeppe Ragnar
Daelken, Benjamin
Guenther, Oliver
Ladel, Christoph
Michaelis, Martin
Conaghan, Philip G
author_facet Eckstein, Felix
Hochberg, Marc C
Guehring, Hans
Moreau, Flavie
Ona, Victor
Bihlet, Asger Reinstrup
Byrjalsen, Inger
Andersen, Jeppe Ragnar
Daelken, Benjamin
Guenther, Oliver
Ladel, Christoph
Michaelis, Martin
Conaghan, Philip G
author_sort Eckstein, Felix
collection PubMed
description OBJECTIVE: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results. METHODS: Patients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months. The primary analysis was at year 2, with follow-up at years 3, 4 and 5. Additional post hoc exploratory analyses were conducted in patients with baseline minimum radiographic joint space width 1.5–3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain 40–90, a subgroup at risk (SAR) of progression. RESULTS: 378 (69%) patients completed the 5-year follow-up. A significant dose-response in total femorotibial joint cartilage thickness with sprifermin (trend test, p<0.001) and a 0.05 mm mean difference with sprifermin 100 µg q6mo versus placebo (95% CI 0.00 to 0.10; p=0.015) were sustained to year 5. WOMAC pain scores improved ~50% from baseline in all groups. No patient in the 100 µg q6mo group had replacement of the treated knee. 96%–98% of patients receiving sprifermin and 98% placebo reported adverse events, most were mild or moderate and deemed unrelated to treatment. Adverse event-related study withdrawals were <10%. Differentiation in WOMAC pain between sprifermin 100 µg q6mo and placebo in the SAR (n=161) at year 3 was maintained to year 5 (−10.08; 95% CI −25.68 to 5.53). CONCLUSION: In the longest DMOAD trial reported to date, sprifermin maintained long-term structural modification of articular cartilage over 3.5 years post-treatment. Potential translation to clinical benefit was observed in the SAR. TRIAL REGISTRATION NUMBER: NCT01919164
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spelling pubmed-82925622021-08-05 Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study Eckstein, Felix Hochberg, Marc C Guehring, Hans Moreau, Flavie Ona, Victor Bihlet, Asger Reinstrup Byrjalsen, Inger Andersen, Jeppe Ragnar Daelken, Benjamin Guenther, Oliver Ladel, Christoph Michaelis, Martin Conaghan, Philip G Ann Rheum Dis Osteoarthritis OBJECTIVE: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results. METHODS: Patients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months. The primary analysis was at year 2, with follow-up at years 3, 4 and 5. Additional post hoc exploratory analyses were conducted in patients with baseline minimum radiographic joint space width 1.5–3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain 40–90, a subgroup at risk (SAR) of progression. RESULTS: 378 (69%) patients completed the 5-year follow-up. A significant dose-response in total femorotibial joint cartilage thickness with sprifermin (trend test, p<0.001) and a 0.05 mm mean difference with sprifermin 100 µg q6mo versus placebo (95% CI 0.00 to 0.10; p=0.015) were sustained to year 5. WOMAC pain scores improved ~50% from baseline in all groups. No patient in the 100 µg q6mo group had replacement of the treated knee. 96%–98% of patients receiving sprifermin and 98% placebo reported adverse events, most were mild or moderate and deemed unrelated to treatment. Adverse event-related study withdrawals were <10%. Differentiation in WOMAC pain between sprifermin 100 µg q6mo and placebo in the SAR (n=161) at year 3 was maintained to year 5 (−10.08; 95% CI −25.68 to 5.53). CONCLUSION: In the longest DMOAD trial reported to date, sprifermin maintained long-term structural modification of articular cartilage over 3.5 years post-treatment. Potential translation to clinical benefit was observed in the SAR. TRIAL REGISTRATION NUMBER: NCT01919164 BMJ Publishing Group 2021-08 2021-05-07 /pmc/articles/PMC8292562/ /pubmed/33962962 http://dx.doi.org/10.1136/annrheumdis-2020-219181 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Osteoarthritis
Eckstein, Felix
Hochberg, Marc C
Guehring, Hans
Moreau, Flavie
Ona, Victor
Bihlet, Asger Reinstrup
Byrjalsen, Inger
Andersen, Jeppe Ragnar
Daelken, Benjamin
Guenther, Oliver
Ladel, Christoph
Michaelis, Martin
Conaghan, Philip G
Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title_full Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title_fullStr Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title_full_unstemmed Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title_short Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study
title_sort long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the forward study
topic Osteoarthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292562/
https://www.ncbi.nlm.nih.gov/pubmed/33962962
http://dx.doi.org/10.1136/annrheumdis-2020-219181
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