No Precision in Targeting ILD Treatments
“The situation we face with ILD is that there are no validated biomarkers for disease staging, prediction of disease progression or drug response. Right now we can’t match the individual patient to the right therapy,” Dr. Maurer tells The Rheumatologist. “These patients are heterogeneous, with different targets of action. We have no way of predicting which patient will benefit from which treatment.” This requires managing ILD on a trial-and-error basis. “We need tools to define the best therapy for the individual patient,” she says.
Marco Matucci-Cerinic, director of the Division of Medicine and Rheumatology at the University of Florence, Italy, and current chair of the European League Against Rheumatism Scleroderma Trial and Research Group, says the Swiss preclinical proof-of-concept study offers new insights and opens new avenues for research. These will need to be validated and cross-checked in larger patient populations with patient stratification according to subsets of lung involvement.
“This is novel research. For the first time, particular receptors have been linked definitively and correlated to the clinical picture of lung involvement and the pathology of lung tissue in interstitial pneumonia. These receptors are very important to us,” Dr. Matucci-Cerinic explains.
This concept can identify pathophysiologic key molecules and, thus, eventually point to targeted approaches to treatment. “This research could have translation in clinical practice within the next few years and on how the illness is perceived,” he continues.
“I would also like to focus our interest on somatostatin receptors. These are expressed primarily in the nervous system but are also seen in immune cells like leukocytes. That raises the question of how much the peripheral nervous system may be involved in the pathogenesis of ILD in connective tissue disease,” Dr. Matucci-Cerinic says.
Next Steps
Dr. Maurer says her research group, together with the co-principal investigator at CRS, Cristina Mueller, PhD, aims to launch a clinical trial in 2019 using nuclear imaging, looking at targets beyond those used in this study, integrin αvβ3 and the somatostatin receptor. “We are also thinking of the folate receptor subtype β, which is expressed on activated macrophages. These other targeted radiotracers are available today. What’s needed is the proof of concept,” she says.
She expresses hope for advances in the treatment of ILD. “With so much research elucidating the pathophysiology of this disease, we can expect the approval of specific therapies in the next two or three years. Several compounds are now being tested in phase 2 or 3 trials. It’s now time to think about developing diagnostic tools that will allow us to substratify patients for individualized treatment,” Dr. Maurer says.
“I think medical imaging and nuclear medicine, in particular, have a lot of potential that we are only starting to explore,” Dr. Maurer states. Compared with lung biopsies, these are non-invasive methodologies, and they don’t require high doses of radiation. She is confident that within the next five years, subtyping patients based on predicted drug responses will be possible, which will take us one step closer to precision medicine.