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Review
. 2025 Jan 28;7(2):100572.
doi: 10.1016/j.ocarto.2025.100572. eCollection 2025 Jun.

The inflammatory endotype in osteoarthritis: Reflections from the 2024 OARSI clinical trials symposium (CTS) with a special emphasis on feasibility for clinical development

Morten Asser Karsdal  1 , Lucio C Rovati  2   3 , Jeyanesh Tambiah  4 , Olga Kubassova  5 , Christoph Ladel  6 , Francis Berenbaum  7 , Anne-Christine Bay-Jensen  1 , Lachy Mclean  8 , Richard Loeser  9 , Ali Mobasheri  10   11   12   13 , Virginia B Kraus  14
Affiliations
Review

The inflammatory endotype in osteoarthritis: Reflections from the 2024 OARSI clinical trials symposium (CTS) with a special emphasis on feasibility for clinical development

Morten Asser Karsdal et al. Osteoarthr Cartil Open. .

Abstract

Objective: The inflammatory endotype is arguably one of the most well-established endotype in osteoarthritis (OA). While endotyping holds promise for advancing drug development, numerous potential challenges must be considered, addressed and resolved before successful clinical outcomes can be achieved.

Design: Since 2017, the Osteoarthritis Research Society International (OARSI) has hosted the Clinical Trials Symposium (CTS). Each year, OARSI and the CTS steering committee encourage discussions on selected topics among a broad range of stakeholders, including regulators, drug developers, clinicians, clinical researchers, biomarker specialists, and basic scientists, with the aim of advancing drug development in the OA field.

Results: This report highlights the ongoing tension between academia's "blue ocean" strategy and the feasibility-driven approach of drug developers, all within the context of scientific efforts to find effective solutions. Understanding the needs, goals, constraints, and opportunities of all involved stakeholders is crucial for defining optimal drug development strategies for OA.

Conclusion: A multidisciplinary, collaborative approach is essential for developing effective OA treatments, balancing scientific discovery with regulatory and clinical feasibility.

Keywords: Clinical development; Endotype; Inflammation; Osteoarthritis; Phenotype; Stratification.

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Conflict of interest statement

The authors declare no competing interests related to this work.

Figures

Fig. 1
Fig. 1
The contribution of inflammation to the osteoarthritis iceberg. Inflammation promotes the development of osteoarthritis (OA) at the early pre-symptomatic phase in response to acute joint injury (macro-injury) and to micro-injury resulting from abnormal mechanical loading of the joint. Inflammatory mediators or the changes in matrix proteins resulting from inflammation can serve as soluble biomarkers at pre-symptomatic and symptomatic phases of OA. Imaging modalities such as MRI can detect synovitis and other structural features that result from inflammation. Finally, inflammation contributes to the development of OA symptoms, in particular pain. Adapted with permission from Hochberg et al. Osteoarthritis. In: Liebowitz J, Seo P, (eds) Clinical Innovation in Rheumatology, Past, Present, and Future. 47–63 (CRC Press/Taylor and Francis, 2023). Figure created with BioRender, agreement number RA27A7932D (VBK).
Fig. 2
Fig. 2
The inflammatory endotype is manifest in a subgroup of patients with (A) high-grade immune-related systemic or local inflammation and/or metabolic dysfunction, leading to (B) higher release of an array of cytokines, chemokines and growth factors). This in turn results in an upregulation of proteolytical enzymes and local expression or activation of growth factors (C). This leads to the release of post-translation modification from the joint into the circulation (D).
Fig. 3
Fig. 3
Stochastic selection of patients will result in more patient endotypes selected and thus, potentially a lower response rate. In contrast, selecting a more treatment targeted endotype may enrich for treatment responders, thereby enhancing the efficacy and safety ratio. Modified from [58,81].
See this image and copyright information in PMC

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