Why some rheumatoid arthritis patients respond poorly to biologics

Members do not see these Ads. Sign Up.

Press Release
Mayo Clinic research sheds light on why some rheumatoid arthritis patients respond poorly to biologics
November 14, 2016

 

The implications of biologic therapy for elective foot and ankle surgery in patients with rheumatoid arthritis
Ross Diaper et al
The Foot; 27 January 2017

 

NEWS RELEASE 27-OCT-2020
New research predicts whether rheumatoid arthritis patients will respond to treatment
A new study led by researchers at Queen Mary University of London provides potential novel biomarkers for predicting patient responsiveness to disease modifying anti-rheumatic drugs (DMARDs).

A new study led by researchers at Queen Mary University of London provides potential novel biomarkers for predicting patient responsiveness to disease modifying anti-rheumatic drugs (DMARDs).

Rheumatoid Arthritis (RA) patients are commonly treated with disease modifying anti-rheumatic drugs (DMARDs) despite the fact that up to 50% of patients are unresponsive to treatment. Up until now, there has been no way to find out whether a patient will effectively respond to treatment.

The new study, published in the science journal Nature Communications, demonstrates that by measuring levels of certain small molecules produced from essential fatty acids in a patient's blood that are involved in regulating inflammation (known as 'specialized pro-resolving mediators'), predictions can be made about an individual's ability to respond to these drugs.

Lead author Professor Jesmond Dalli from Queen Mary University of London said: "Currently a large proportion of patients with RA are unresponsive to DMARDs and are therefore unnecessarily exposed to their side effects. In addition, it can currently take up to six months from treatment initiation to determine whether someone will or will not respond to these medicines. For the patients who do not respond to the treatment, the disease gets worse before they are able to find a treatment that is more likely to work for them.

"The research was conducted using blood from healthy RA patients who were both responsive and unresponsive to treatment. The blood was collected before treatment initiation or six months after treatment commenced. We then measured the levels of protective molecules using mass spectrometry-based methodologies that were coupled with artificial intelligence methodologies to identify molecules that can predict responses to treatment."

The paper recommends that the blood levels of the mediator group identified in the study should be measured to predict the responsiveness RA patients to DMARD treatment.

The team plan to conduct a larger study to evaluate if these initial findings can be applied to a bigger patient group.

 

NEWS RELEASE 25-NOV-2020
New breakthrough in the treatment of rheumatoid arthritis

People with Rheumatoid Arthritis (RA) could soon benefit from a new drug treatment that not only suppresses inflammation but also significantly reduces patient reported pain scores. Otilimab is a monoclonal antibody, biologic drug, which targets and suppresses the inflammatory cytokine GM-CSF.

In a multicentre, dose-ranging trial, led by Professor Chris Buckley at the Universities of Oxford and Birmingham, and sponsored by the Pharmaceutical company GSK, researchers explored the clinical effects of otilimab to prevent inflammation, tissue damage and pain in people with RA.

The study evaluated the effects of five doses of otilimab (22·5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) versus a placebo. 222 patients with active RA received weekly subcutaneous injections for 5 weeks, which was reduced to every other week for one year. A range of patient reported outcomes for function and pain were measured. Otilimab treatment led to a rapid reduction in tender and swollen joints but patients also reported very significant improvements in pain scores.

Professor Buckley, Kennedy Professor of Translational Rheumatology at the Universities of Oxford and Birmingham said: "The assumption has always been that if drugs suppress inflammation, they will also help suppress pain, but this hasn't always been the case. Now, for the first time we are seeing a biologic therapy, the first in the rheumatoid space, that offers two for the price of one. It's suppressing inflammation, but it's also helping pain, and that's very important to the patient."

The trial was novel in that it offered an escape arm for patients receiving the placebo or in whom the drug dose to which they were randomised did not achieve a reduction in their disease activity. "One of the problems with placebo arms is it's hard to get people to go into the study if they know they might get a dummy drug ," said Prof. Buckley. "In this trial, if a patient wasn't seeing improvements after 12 weeks they were automatically transferred to the highest dose of otilimab at 180 mg and we were able to then see the improvements."

This study helped lay the infrastructure groundwork for the CATALYST Trial, also a collaboration between Oxford and Birmingham, which is measuring the effectiveness of GM- CSF and another anti-inflammatory drug (anti TNF) in the treatment of COVID-19.

###

The results of the trial have been recently published in The Lancet Rheumatology.

The research was funded by GSK.