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ABSTRACT
Introduction
Osteoarthritis is a chronic, degenerative, and debilitating disease associated with significant long-term morbidity and disability. The pathogenesis of osteoarthritis is not completely understood but involves an interplay between environmental risk factors, joint mechanics, abnormal pain pathways and upregulation of inflammatory signaling pathways. Current therapeutic options for patients are limited to conservative management, minimal pharmacological options or surgical management, with significant caveats to all approaches.
Areas covered
In this review we have set out to investigate current phase II/III clinical trials by undertaking a pubmed search. Examined clinical trials have explored a myriad of potential therapeutics from conventional disease-modifying anti-rheumatic drugs and biologics usually used in the treatment of inflammatory arthritides, to more novel approaches targeting inflammatory pathways implicated in osteoarthritis, cartilage degeneration or pain pathways.
Expert opinion
Unfortunately, most completed phase II/III clinical trials have shown little impact on patient pain scores, with the exception of the traditional DMARD methotrexate and Sprifermin. Methotrexate has been shown to be beneficial when used in the correct patient cohort (MRI proven synovitis). Sprifermin has the longest follow-up data of 5 years and has been shown to reduce loss of MRI-measured cartilage thickness and pain scores.
Disclaimer
As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.Article highlights
There are multiple DMOAD’s in development which target inflammation, cartilage breakdown and regeneration and block pain pathways.
Repurposing conventional and biologic DMARDs have been attempted with varying results.
Identifying subtypes of OA according to phenotype may help with success in future trials.
Abbreviations
| ACR | = | American college of rheumatology |
| CGRP | = | calcitonin-gene-related peptide |
| CMFTC | = | central medial tibiofemoral compartment cartilage |
| CNTX-4975 | = | Intraarticular high purity synthetic trans-capsaicin |
| COL2A | = | collagen 2 A |
| DMARDS | = | disease-modifying anti-rheumatic drugs |
| DMOADS | = | disease-modifying osteoarthritis drugs |
| FDA | = | Food and drug administration |
| EMA | = | European medicines agency |
| FGF-18 | = | Fibroblast growth factor |
| GM-CSF | = | granulocyte-macrophage colony-stimulating factor |
| HsCRP | = | high sensitivity CRP |
| iNOS | = | nitric oxide synthase inhibitor |
| KLG | = | Kellgren and Lawrence classification of osteoarthritis |
| KOOS | = | knee injury and osteoarthritis outcome score |
| MEPE | = | matrix extracellular phosphoglycoprotein |
| MMPs | = | matrix metalloproteinases |
| NGF | = | nerve growth factor |
| NICE | = | National Institute for Health Care Excellence |
| NRS | = | numeric rating score |
| NSAIDs | = | non-steroidal anti-inflammatory drugs |
| OA | = | osteoarthritis |
| OARSI | = | osteoarthritis research society international |
| PGA | = | patient global assessment |
| PRP | = | platelet rich plasma |
| RPOA | = | rapidly progressive osteoarthritis |
| SAR | = | subtype at risk of progression |
| TCR | = | T-cell receptor |
| TGFB1 | = | transforming growth factor 1 |
| VAS | = | visual analogue scale |
| WOMAC | = | Western Ontario and McMaster Universities osteoarthritis index |
Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.