Cargando…
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....
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783724849916542976 |
---|---|
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 |
format | Online Article Text |
id | pubmed-8292562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ecksteinfelix longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT hochbergmarcc longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT guehringhans longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT moreauflavie longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT onavictor longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT bihletasgerreinstrup longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT byrjalseninger longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT andersenjepperagnar longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT daelkenbenjamin longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT guentheroliver longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT ladelchristoph longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT michaelismartin longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy AT conaghanphilipg longtermstructuralandsymptomaticeffectsofintraarticularsprifermininpatientswithkneeosteoarthritis5yearresultsfromtheforwardstudy |