Hans Guehring1, Flavie Moreau2, Benjamin Daelken1, Christoph Ladel1, Oliver Guenther1, Asger Reinstrup Bihlet3, Wolfgang Wirth4, Felix Eckstein4, Marc Hochberg5, Philip G Conaghan6. 1. Merck KGaA, Darmstadt, Germany. 2. EMD Serono Research and Development Institute, Inc., Billerica, MA, USA. 3. NBCD A/S, Herlev, Denmark. 4. Chondrometrics GmbH, Ainring, Germany; Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy & Cell Biology, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria; Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, Salzburg, Austria. 5. University of Maryland School of Medicine, Baltimore, MD, USA. 6. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK. Electronic address: P.Conaghan@leeds.ac.uk.
Abstract
OBJECTIVE: To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin. METHODS: Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40-90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint. RESULTS: The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]). CONCLUSIONS: Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials. CLINICAL TRIAL REGISTRATION: NCT01919164.
OBJECTIVE: To assess pain outcomes and cartilage thickness change in a subgroup at risk (SAR) of further progression in the FORWARD trial of knee osteoarthritis patients treated with sprifermin. METHODS: Patients were randomised 1:1:1:1:1 to: sprifermin 100 µg every 6 months (q6mo), 100 µg q12mo, 30 µg q6mo, 30 µg q12mo, or placebo for 18 months. SAR was defined as baseline medial or lateral minimum joint-space width (mJSW) 1.5-3.5 mm and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 40-90 units. Follow-up to 3 years was included in the analysis. Treatment benefit was explored by repeated measures, linear dose-effect trends by timepoint. RESULTS: The SAR comprised 161 (29%) of 549 patients. Mean difference (95% CI) in WOMAC pain at year 3 for sprifermin 100 µg q6mo vs placebo SAR was -8.75 (-22.42, 4.92) for SAR vs 0.97 (-6.22, 8.16) for the intent-to-treat population. SAR placebo patients lost more cartilage over 2 years than the modified ITT (mITT) placebo arm (mean change from baseline, mm [SD]: -0.05 [0.10] vs -0.02 [0.07]). Net total femorotibial joint thickness gain with sprifermin 100 µg q6mo (adjusted mean difference from placebo [95% CI] was similar in the SAR and in the mITT group: 0.06 [0.01, 0.11] vs 0.05 [0.03, 0.07]). CONCLUSIONS: Selection for low mJSW and moderate-to-high pain at baseline resulted in more rapid disease progression and demonstrated translation of structure modification (with maintained net benefit on total cartilage thickness) into symptomatic benefit. This subgroup may represent a target population for future trials. CLINICAL TRIAL REGISTRATION: NCT01919164.
Authors: Jason S Kim; Silvana Borges; Daniel J Clauw; Philip G Conaghan; David T Felson; Thomas R Fleming; Rachel Glaser; Elizabeth Hart; Marc Hochberg; Yura Kim; Virginia B Kraus; Larissa Lapteva; Xiaojuan Li; Sharmila Majumdar; Timothy E McAlindon; Ali Mobasheri; Tuhina Neogi; Frank W Roemer; Rebecca Rothwell; Robert Shibuya; Jeffrey Siegel; Lee S Simon; Kurt P Spindler; Nikolay P Nikolov Journal: Semin Arthritis Rheum Date: 2022-07-14 Impact factor: 5.431
Authors: F W Roemer; D T Felson; J J Stefanik; G Rabasa; N Wang; M D Crema; T Neogi; M C Nevitt; J Torner; C E Lewis; C Peloquin; A Guermazi Journal: Osteoarthritis Cartilage Date: 2022-02-22 Impact factor: 7.507
Authors: Tonia L Vincent; Tamara Alliston; Mohit Kapoor; Richard F Loeser; Linda Troeberg; Christopher B Little Journal: Clin Geriatr Med Date: 2022-05 Impact factor: 3.529