Osteoarthritis progression identifiable using plasma proteomics signature

7th February 2023

Progression of osteoarthritis based on a marker of cartilage degeneration and pain can be predicted using a plasma proteomic signature

US researchers have identified a plasma proteomic signature that is able to distinguish between patients with osteoarthritis whose disease is progressive or non-progressive and which is superior to currently used methods.

In a global analysis from 2017, it was found that the annual incidence rate of osteoarthritis was 181.2 per 100,000 patients and the authors noted that the burden of disease is increasing in most countries. Currently, there is a need to develop OA prognostic markers and in 2016, researchers identified a method for diagnosing radiographic OA based on a series of serum biomarkers. More recently, a number of systemic biomarkers were identified and deemed to have promise as predictors of both pain and structural worsening of OA. To date, measurement of urinary carboxyl-terminal cross-linked telopeptide of type II collagen (uCTXII) appears to be the strongest predictor of clinically relevant osteoarthritis progression. In the current study, the US team used uCTXII as the ‘best-in-class’ biomarker to evaluate the performance of the proteomic signature they had identified back in 2016, for predicting clinically relevant knee OA progression, defined in terms of both joint structure and pain worsening, over a period of 48 months.

Using a cohort of 596 individuals with OA, the US team set out to measure the effectiveness of their proteomic signature (based on the area under the receiver operating curve, AUC) at distinguishing between progressors and non-progressors.

Osteoarthritis proteomic signature and identification of disease progressors

Data were available for 596 individuals with knee OA with a mean age of 61.6 years (58.7% female) and who at baseline, had moderate to severe radiographic knee OA.

Based on the proteomic signature, containing 13 distinct proteins, the AUC was 73% for differentiating between progressors (based on a measure of both radiographic joint space loss and pain scores). In contrast, the uCTXII model only had an AUC of 58% which was comparable to a model based only on baseline structural OA and the severity of pain (59%).

The researchers went a step further and assessed their proteomic model (but with only 11 proteins) in a second OA cohort and determined an AUC of 70% for distinguishing progressors from non-progressors.

They concluded that their plasma biomarker signature was able to effectively identify clinically relevant knee OA progressors from non-progressors, adding that the proteomic signature may be of value during clinical trials to identify those with the greatest need for treatment.

Citation
Zhou K et al. A “best-in-class” systemic biomarker predictor of clinically relevant knee osteoarthritis structural and pain progression. Sci Adv 2023

Convalescent plasma use reduces hospitalisation in unvaccinated COVID-19 patients

12th April 2022

Convalescent plasma use in people unvaccinated against COVID-19 significantly reduced the need for hospitalisation due to disease progression, according to a US study

Convalescent plasma (CP) use in people unvaccinated against COVID-19 within 9 days of symptom onset, led to a significant reduction in the proportion of individuals requiring hospital admission due to disease progression. This was the conclusion of a randomised, double-blind, controlled trial by a multidisciplinary group of researchers from New York, US.

CP use represents a form of passive antibody therapy that relies on the transfer of pathogen-specific antibodies from a recovered patient for the purpose of preventing or treating disease. It has been successfully used in the past for the management of patients with severe acute respiratory syndrome and early indicators suggested that transfusion of convalescent plasma was safe in hospitalised patients with COVID-19.

Furthermore, preliminary results among patients hospitalised with severe COVID-19 were encouraging, with the authors of one study concluding that convalescent plasma is potentially effective against COVID-19.

Nevertheless, in a Cochrane database living systematic review in May 2021, the authors commented on how they had high certainty in the evidence that convalescent plasma for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement.

Whether CP might help prevent disease worsening in those with less severe disease is uncertain and the available evidence is mixed. For example, one study found that early administration of high-titer convalescent plasma against COVID-19 to mildly ill older adults, reduced the progression of the illness.

By contrast, in a study where the authors set the primary outcome as disease progression within 15 days after randomisation, it was concluded that administration of convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of COVID-19 did not prevent disease progression.

With some uncertainty over the role of CP in less severe disease, for the present study, the US team examined the value of administering CP within 9 days of COVID-19 symptom onset to determine if the treatment prevented disease progression leading to hospitalisation.

They recruited adults testing positive for the virus and randomised them 1:1 to either CP or control plasma, with both transfused over 1 hour period within 24 hours of enrolment. The primary outcome was COVID-19-related hospitalisation within 28 days after the transfusion.

Convalescent plasma use and disease progression

A total of 1181 individuals with a median age of 43 years (57.2% female) were included with 592 given CP and median time from symptom onset to transfusion was 6 days. Co-morbidities were well matched and among those receiving CP included hypertension (23%) and those with a BMI > 35 (16.4%) with 83.3% of those given CP (and a similar proportion in the control group) unvaccinated against COVID-19.

The primary outcome occurred in 2.9% of those receiving CP and 6.3% of those given control plasma (absolute risk reduction = 3.4% (95% CI 1.0 – 5.8%, p = 0.005). Among those who were hospitalised, virtually all (53 of 54) were unvaccinated against COVID-19.

The authors concluded that giving convalescent plasma within 9 days of COVID-19 symptom onset reduced disease progression leading to hospitalisation.

Citation
Sullivan DJ et al. Early Outpatient Treatment for Covid-19 with Convalescent Plasma N Engl J Med 2022