Day: November 26, 2020

New Drug Relieves Rheumatoid Arthritis Pain

A new drug, otilimab, has shown effectiveness in treating rheumatoid arthritis (RA). Otilimab is a human monoclonal antibody which inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a large driver of immune-mediated inflammatory conditions.

The drug is currently being tested on its ability to suppress inflammation, tissue damage and pain in RA sufferers.

A multicentre, dose-ranging trial conducted with the drug. Participants were administered subcutaneous injections with one of five different dosages of otilimab (22.5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) or placebo weekly for five weeks. Thereafter, they received injections once every two weeks for one year. The results showed a rapid reduction in tenderness and swelling, and a very high reduction in pain.

The study was unusual in that it offered an escape arm. It is often difficult to recruit participants when they know they may be receiving a dummy injection, and so if, after 12 weeks the participants  on the placebo arm derived no benefit, they were transferred to the highest dose arm of 180mg.

Source: Medical Xpress

Journal information: Christopher D Buckley et al, Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study, The Lancet Rheumatology (2020). DOI: 10.1016/S2665-9913(20)30229-0

Osteoporosis Drug Enhances Natural Bone Formation

A new osteoporosis drug, NaQuinate, that treats osteoporosis by enhancing its response to weight bearing, has completed its first human clinical trial. 

NaQuinate is a naphthoquinone carboxylic acid, and is found naturally as a Vitamin K metabolite. It has been shown in mouse models that NaQuinate responds synergistically to mechanical loading, building bone density. In a separate trial, the efficacy of NaQuinate is being evaluated against that of bisphosphonates without loading and anabolics with loading.

Haoma Medica’s Chief Medical Officer, Dr Cenk Oguz, said: ”We are delighted that the first-in-human study has completed its last dosing. There were no significant safety or tolerability concerns up to the highest doses tested which underlines our expectation that NaQuinate is safe and well tolerated.”
Haoma Medica’s CEO,  Dr Steve Deacon, said:”Our pre-clinical research has revealed an exciting feature of NaQuinate where it appears to have the capacity to work in harmony with the body’s natural response to weight bearing exercise to synergistically enhance bone formation when and where required – now that would be a ‘smart’ drug. Together with the safety data from this first-in-human study, this supports the potential that NaQuinate treatment could provide a safe, novel and smart therapeutic approach to bone disorders like osteoporosis and better maintain healthy skeletal aging.”

Source: PR NewsWire

APPs Can Contribute More in Emergency Departments

A recent study investigated how advanced practice providers (APPs) are being underutilised in emergency department settings.

The study, published in Academic Emergency Medicine concluded that, in comparison to ED physicians,  APPs such as physician assistants and registered nurse anaesthetists, see fewer complex patients and generate less value per unit hour.

The study, which investigates the impact of APPs in the ED on productivity, flow, safety, and experience, is the first of its kind.

However, the study suggests that APPs can be better integrated into EDs, minimising any adverse impact on ED flow, clinical quality, or patient experience. Furthermore, APPs, currently used for low-acuity cases, can add value with independent assessment of critical ED cases.

Source: News-Medical.Net

Journal information: Pines, J. M., et al. The Impact of Advanced Practice Provider Staffing on Emergency Department Care: Productivity, Flow, Safety, and Experience, Academic Emergency Medicine (2020) doi.org/10.1111/acem.14077

New Minimally Invasive Way to Sample Interstitial Fluid

A new method to extract dermal interstitial fluid (ISF) for analysis has been reported. ISF contains a large number of biomarkers which can be used for diagnosis.

The minimally invasive process uses an array of almost invisibly small needles, approximately one quarter of a millimetre long. These were pressed to the skin and suction applied. Care needed to be taken so that the needles did not poke into microcapillaries in the skin and thus contaminate the sample with blood. 

Blood is often used for testing, comprising some 6% of the human body’s fluids, but some 10 000 compounds are found in ISF and 12% of the chemicals are not found in the blood. With the technique, the researchers were also able to measure the effects of glucose and caffeine, which are dynamically active. Traditional methods used to extract are quite invasive; using a needle to withdraw ISF from a vacuum-induced blister, or surgically inserting tubes underneath the skin.

Although the procedure is still time consuming, taking some 20 minutes per patient, it compares to the ~40 minutes required to form a vacuum blister in some ISF sampling protocols. The small needle injuries healed within a day, and there was minimal irritation.

This form of testing could have many applications, such as skin toxicological studies and monitoring glucose levels.

The journal article has been published in Science Translational Medicine.

Source: News-Medical.Net

Gut Microbiota Have Large Effects on Immune System

For the first time, immune cells in the bloodstream have been shown to be affected by the makeup of gut microbiota.

In recent years, there has been increased interest in gut microorganisms and their influence on human health, partly as a result of improvements in the ability to study them. Much prior understanding of gut microbiota on the immune system comes from animal studies; this study was able to examine the effects in humans. This study used data from allogeneic stem cell and bone marrow transplants (BMTs), where the patient’s blood formation system is destroyed by radiation or chemotherapy and replaced with stem cells from a donor’s bone marrow. The patient is given antibiotics until the transplanted cells are able to re-establish the immune system, the gut microbiota being destroyed in the process and then re-establishing once the antibiotics are withdrawn. Over a period of ten years, a multidisciplinary team with the Memorial Sloan Kettering Cancer Center took blood and faecal samples from BMT patients.

Study author Dr Joao Xavier said, “Our study shows that we can learn a lot from stool—biological samples that literally would be flushed down the toilet. The result of collecting them is that we have a unique dataset with thousands of datapoints that we can use to ask questions about the dynamics of this relationship.”
“The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyse the associations between these two systems,” lead author Dr Jonas Schluter said.

A higher diversity of microbiota was shown to lower the risk of death following a BMT, and a lower diversity increased the risk of graft-versus-host disease, a potentially fatal condition where the transplanted marrow attacks the host’s body.

“Because experiments with people are often impossible, we are left with what we can observe,” Dr. Schluter noted. “But because we have so many data collected over a period of time when the immune system of patients as well as the microbiome shift dramatically, we can start to see patterns. This gives us a good start toward understanding the forces that the microbiota exerts on the rebuilding of the immune system.”

Source: Medical Xpress

Journal information: Jonas Schluter et al. The gut microbiota is associated with immune cell dynamics in humans, Nature (2020). DOI: 10.1038/s41586-020-2971-8

Questions Raised over Oxford’s Unusual Vaccine Regimen

The recent announcement of the Oxford’s and AstraZeneca’s vaccine trial being 70% effective up to 90% effective has raised some pointed questions.

The trial had two treatment arms, one receiving two full doses of the AZD1222 vaccine and a half dose plus a full dose, with the doses being administered 28 days apart. The “half dose then full dose”  treatment arm reported the 90% protection. The problem was that the trial was never meant to have such an arm. 

It was noticed that some participants were only receiving a half dose because they were experiencing fewer effects than expected such as arm pain and headache. This was subsequently corrected so that they would still receive the full dose on the second administration.

Of particular concern is that the “90% effectiveness” is based on a much smaller subset of the trial participants, with a correspondingly higher statistical uncertainty. So much so that there is statistical overlap with their lower effectiveness of 62% quoted for the two full doses. Furthermore, the participants were from the initial stages of the vaccine trial, where they were aged 18-55 and therefore have little applicability to the results of the main trial which included older age groups as well. 

The details of exactly why the half-measure doses came to be administered in the first place have not been revealed by Oxford or AstraZeneca. Meanwhile in the US, a Phase III of the trial is being rolled out with 40 000 participants, and the “half dose then full dose” regimen may be included – however, uncertainty about it and whether it isn’t a statistical fluke will have to be cleared up first.

Source: Ars Technica