Monique Chalem’s key takeaways on PANLAR’s session “OA phenotypes and biomarkers”1
Dr. Chalem gives us insights about fresh perspectives on osteoarthritis (OA) that emerged during the dynamic PANLAR “OA phenotypes and biomarkers” session1, where experts explored how biomarkers, endotypes, phenotypes and theratypes are shaping clinical decision making, paving the way for the future of precision medicine and personalised OA care.
Management of (OA) relies mostly in measuring symptoms and functional capacity. Recent advances in molecular biology and the comprehension of the role of inflammation have transformed our understanding of OA, yet halting disease progression remains an unmet need. A growing acknowledgement of the molecular, structural, and clinical heterogeneity of OA, in which patient subtypes –defined by distinct phenotypes, endotypes, and theratypes– are driving a shift towards precision medicine.
“Typing” the future of OA management: phenotypes, endotypes, theratypes and regiotypes
Phenotype is a clinically observable characteristic or trait of disease. There may be overlap among phenotypes because they are not mutually exclusive; for example, a patient may exhibit features of several phenotypes, e.g., post-traumatic, senescent, and metabolic.
Understanding the molecular endotypes that influence clinical phenotypes is a critical step for the stratification of patients with osteoarthritis (OA) into therapeutic subtypes that can help the development of targeted disease-modifying OA drugs (DMOADs) to provide genuine, long-term clinical benefit2.
Current research has identified several endotype-driven phenotypes, including those associated with:
- Low tissue turnover
- Extensive structural damage
- Systemic inflammation
These distinctions have important implications for the development and evaluation of targeted interventions aimed at slowing disease progression.
A theratype is defined as the prediction of treatment response based on a particular disease endotype. Results from randomised controlled trials generally reflect the average treatment effect in the study population but frequently do not consider heterogeneous responses across patients. If a specific subgroup of patients benefits from a treatment while another does not, the overall study results may appear largely negative if the responsive subgroup is not properly identified.
Incorporating endotype data may enable more accurate predictions of which patients are most likely to benefit from specific interventions, minimizing therapeutic inertia and allowing for a better interpretation of clinical outcomes.
The novel concept of regiotype is now introduced to reflect how environmental and socioeconomic issues can influence disease characteristics across regions.
Precision for decision; shaping the future for OA Management
Therapeutic strategies in OA are becoming more diverse, reflecting a deeper understanding of the disease complexity. Recent investigational approaches are exploring pathways involved in inflammation, cartilage repair, and bone remodelling, driving future strategies towards individualised regimens based on patient-specific disease drivers.
«In this era of precision medicine, having validated biomarkers to inform Clinical decision making is more important than ever.»
Dr. Chalem
Biomarkers can give us a better understanding of disease processes, opportunities for an early diagnosis, more accurate predictions and endotype-based patient selection for drug trials. The biomarker approach could potentially drive stratification for OA clinical trials and contribute to precision medicine strategies for OA progression in the future.
In addition to recent advances in inflammation, metabolic, bone turnover and cartilage environment biomarkers, attention is now turning to other newer candidates such as non-coding RNAs3.
The future of OA treatments will be shaped by integrating clinical phenotypes, molecular endotypes with biomarker profiles and theratypes to tailor therapies to individual patients. By combining these data, it will be possible to move beyond one-size fits all approaches and develop targeted and personalised interventions that address the underlying drivers of each patient’s disease, resulting in better outcomes and quality of life.
Bibliography
- “Osteoarthritis phenotypes and biomarkers” PANLAR science session. PANLAR 2025; 2025 April 23-26, Mexico City, Mexico.
- Mobasheri A, Loeser R. Clinical phenotypes, molecular endotypes and theratypes in OA therapeutic development. Nat Rev Rheumatol 2024; 20(9):525-526.
- Ali S, Peffers M, Ormseth M, et al. The non-coding RNA interactome in joint health and disease. Nat Rev Rheumatol 2021;17(11):692-705.
