ArticleArthritis research & therapy2026
Therapeutic subtypes of knee osteoarthritis: differential treatment effects among predicted endotypes in past clinical trials.
Article in Arthritis research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Not yet cited in PubMed.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Multi-Center, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Salmon Calcitonin in the Treatment of Subjects With Knee Osteoarthritis
A Randomised, Double-blind Placebo-controlled Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of MIV-711 in Knee Joint Osteoarthritis
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Single-Dose Study of UBX0101 in Moderate to Severe, Painful Osteoarthritis of the Knee
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13 authors.
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Abstract
backgroundMolecular endotyping may facilitate the successful development of personalized treatments of knee osteoarthritis (KOA). The aim of this exploratory and hypothesis-generating study was to develop a clinically actionable tool for predicting molecular endotypes of KOA using blood-based biomarkers, and to explore the potential for differential treatment effects across biomarker-based endotypes in prior phase II-III KOA drug trials.
methodsFourteen biomarkers from 226 KOA participants from IMI-APPROACH were assessed for a multinomial logistic regression model to predict structural damage, inflammation, and low tissue turnover endotypes. An optimized panel of six serum biomarkers (C2M, C3M, N-MID, PRO-C2, PRO-C4, sCTX-I) was identified quantitatively by testing all biomarker combinations in models adjusting for age, sex, and BMI. These biomarkers were used for endotype predictions in KOA participants from the randomized placebo-controlled trials MIV-711 (n = 244) (NCT02705625), salmon calcitonin (n = 947) (NCT00486434), and UBX0101 (n = 175) (NCT04129944).
resultsThe structural damage endotype showed the greatest numerical 26-week reduction in NRS knee pain when treated with MIV-711 (-6.46%; 95% CI: -16.23%, 3.31%). Notably, only the structural damage endotype had a significant two-year reduction in WOMAC pain when treated with salmon calcitonin (-6.19%; 95% CI: -10.55%, -1.83%). Considering the subset treated with salmon calcitonin with the top 20% highest probability of belonging to the structural damage endotype, a 9-15% reduction in standard deviation of the two-year change in WOMAC pain was observed. Enriching the trial for this subset with lower outcome variability could have led to an 18-28% reduction in the needed sample size.
conclusionsThis exploratory study suggests the feasibility of predicting KOA endotypes using a minimal panel of tissue-turnover biomarkers. The observed treatment effects of anti-bone resorptive treatments and reduced outcome variability in the structural damage endotype may subtly indicate that aligning treatments with endotypes and drug modes of action can possibly enhance their therapeutic efficacy. Further investigation is needed to establish the true clinical utility of biomarker-based endotyping. Endotype-informed trial design and recruitment may represent a promising strategy to increase the likelihood of success in future KOA clinical trials.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.