Search

Purpose: The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) consortium intends to prospectively describe in detail, preselected patients with knee osteoarthritis (OA), using conventional and novel clinical, imaging, and biochemical markers, to support OA drug development., Participants: APPROACH is a prospective cohort study including 297 patients with tibiofemoral OA, according to the American College of Rheumatology classification criteria. Patients were (pre)selected from existing cohorts using machine learning models, developed on data from the CHECK cohort, to display a high likelihood of radiographic joint space width (JSW) loss and/or knee pain progression., Findings to Date: Selection appeared logistically feasible and baseline characteristics of the cohort demonstrated an OA population with more severe disease: age 66.5 (SD 7.1) vs 68.1 (7.7) years, min-JSW 2.5 (1.3) vs 2.1 (1.0) mm and Knee injury and Osteoarthritis Outcome Score pain 31.3 (19.7) vs 17.7 (14.6), except for age, all: p<0.001, for selected versus excluded patients, respectively. Based on the selection model, this cohort has a predicted higher chance of progression., Future Plans: Patients will visit the hospital again at 6, 12 and 24 months for physical examination, pain and general health questionnaires, collection of blood and urine, MRI scans, radiographs of knees and hands, CT scan of the knee, low radiation whole-body CT, HandScan, motion analysis and performance-based tests.After two years, data will show whether those patients with the highest probabilities for progression experienced disease progression as compared to those wit lower probabilities (model validation) and whether phenotypes/endotypes can be identified and predicted to facilitate targeted drug therapy., Trial Registration Number: NCT03883568., Competing Interests: Competing interests: EMvH has nothing to disclose; WEvS reports grants from The Innovative Medicines Initiative Joint Undertaking under Grant Agreement no 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution, during the conduct of the study; MPJ has nothing to disclose; PMJW has nothing to disclose. MK reports grants from IMI-APPROACH, grants from Dutch Arthritis Association, during the conduct of the study; other from GlaxoSmithKline, Pfizer, Merck-Serono, Kiniksa, Abbvie, outside the submitted work; ML reports grants from Inovative Medicines Initative, during the conduct of the study; FJB reports grants from Gebro Pharma, grants from BIOIBERICA, grants from AB Science, grants from Abbvie, grants from Ablynx N.V., grants from Amgen, grants from Archigen Biotech, grants from Boehringer, grants from Bristol-Myers, grants from Celgene Int., grants from Eli Lilly and Company, grants from F. Hoffmann- La Roche, grants from Galapagos, grants from Gedeon, grants from Genentech, grants from Gideal Sciences, NC, grants from Glaxosmithkline, grants from Hospira, grants from INC Research UK, grants from Inventiv Health Clinical, grants from Janssen, grants from Lilly, grants from Nichi-IKO Pharmaceutical, grants from Novartis, grants from ONO Pharma, grants from Pfizer, grants from Pharmaceutical Research, grants from Regeneron, grants from Roche, grants from SA UCB Pharma, grants from Sanofi, grants from TRB Chemedica, grants from UCB Biosciences GMBH, outside the submitted work; In addition, FJB has a patent Molecular block-matching method for gel image analysis issued, a patent Targeting A Specific Receptor On Cells With A Specific Compound For Use In The Treatment And/Or The Prevention Of Osteoarthritis And Rheumatoid Arthritis pending, a patent Genetic markers for osteoarthritis issued, a patent Method for the diagnosis of osteoarthritis issued, a patent Genetic markers for osteoarthritis pending, a patent Method for the diagnosing Arthrosis pending, a patent Method for diagnosing Arthrosis pending, a patent Method for the diagnosis of osteoarthritis pending, and a patent Anti-connexin compounds for use in the prevention and/or treatment of degenerative joint diseases. pending; IKH reports personal fees from AbbVie, grants from Pfizer, outside the submitted work; FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, outside the submitted work; CHL reports other from Merck KGaA, during the conduct of the study; JLo has nothing to disclose; ACB-J reports non-financial support from Nordic Bioscience, personal fees from Nordic Bioscience, during the conduct of the study; AM has nothing to disclose; JLa reports personal fees and other from GlaxoSmithKline, outside the submitted work; and Current employee and shareholder of GlaxoSmithKline; JBo reports grants from Innovative Medicines Initiative (IMI-1), during the conduct of the study; and one of Lygature's other project receives part of its funding directly from Merck KgaA. This project is in the field of schistosomiasis and has no relationship whatsoever with the APPROACH project; HHW has nothing to disclose; ACAM has nothing to disclose; FPJGL has nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Randomised clinical trials to date investigating the efficacy of bisphosphonates in knee osteoarthritis (OA) have found divergent results, with a recent meta-analysis finding no superiority of these drugs over placebo. Whether particular patient subgroups are more likely to benefit from this therapy than others is still unclear. We aim to investigate the effects of bisphosphonates compared with a control group (placebo, no treatment, another active treatment) on clinical and structural outcomes in specific knee OA subpopulations with possible distinct rates of subchondral bone turnover., Methods and Analysis: Medline, Embase, Scopus, Web of Sciences and Cochrane Central Register of Controlled Trials will be searched from inception to February 2018. Randomised clinical trials will be eligible if they reported at least one potential treatment effect modifier at baseline: gender, menopausal status, age, body mass index, radiographic stage, knee pain severity, presence of bone marrow lesions, levels of biochemical markers of bone turnover (serum and/or urinary) and systemic bone mineral density status. Authors of original trials will be contacted to obtain individual patient data from each study. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary outcomes will include pain and radiographic joint space width loss. Studies using other MRI-based assessment of disease progression will also be eligible. Outcomes will be grouped into short-term (≤3 months), intermediate-term (>3 months; ≤12 months) and long-term (>12 months). Regression models will be used, adding an interaction term for each subgroup of interest to determine possible subgroup effects. There was no source of funding for this study., Ethics and Dissemination: Dissemination of our findings is planned to occur through conference presentations, publication in peer-reviewed journals and social media. No formal ethics approval is generally required as no new data collection will be undertaken., Prospero Registration Number: CRD42018093327., Competing Interests: Competing interests: Professor David Hunter reports personal fees from consulting fees from Merck Serono, Flexion and Tissuegene, outside the submitted work. Prof. Bierma-Zeinstra reports grants from the European Union, The Netherlands Organisation for Health Research and Development, Dutch Arthritis Foundation, CZ, Nuts Ohra, Stichting Coolsingel, personal fees from Infirst Healthcare and from Osteoarthritis and Cartilage, outside the submitted work. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)