Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of January 2023.
Prof. Aartsma-Rus reads and comments on the paper titled: Functional and Clinical Outcomes Associated with Steroid Treatment among Non-ambulatory Patients with Duchenne Muscular Dystrophy
Today’s pick is from Journal of Neuromuscular Disease by McDonald et al on retrospective analysis of steroid use on disease progression in non-ambulant Duchenne patients. DOI: 10.3233/JND-221575
Corticosteroids have long been prescribed off-label for Duchenne and they are part of the standards of care. Currently deflazacort is approved for Duchenne in the USA – elsewhere both prednisone and deflazacort are used off-label. Steroid treatment slows down disease progression.
Comparative analysis of deflazacort vs prednisone vs no steroids has mostly been done in ambulant patients, showing a clear delay in loss of ambulation and decline in ambulatory function for either steroid.
Notably, prednisone is used both daily or in an on/off regimen (often 10 days on 10 days off), while deflazacort is primarily used daily. The on/off regimen is less effective in slowing down disease progression than daily steroids, but also is associated with less side effects.
Here authors focus on analyzing the effect of steroids in disease progression in non-ambulant patients using data from the Prosensa/BioMarin natural history study. 86 non-ambulant patients were included, 40 using deflazacort, 29 prednisone and 17 no steroids. 95% of deflazacort patients were on a daily regimen, compared to 41% of prednisone patients. Most patients stayed on the regimen for the duration of the study. Patients were ~13.4 at the start of the study and followed for an average 21 months.
Steroid treated patients had better forced vital capacity, cough peak flow and heart function (LVEF) and the upper limb performance (PUL test) and slowed less decline for all these outcomes. For most outcomes there was no difference between deflazacort and prednisone.
For the PUL test, deflazacort did better than prednisone. Authors discuss that this is likely a dosing effect: deflazacort patients were generally treated with a higher equivalent dose than prednisone for daily treatment and part of prednisone patients was on on/off regimen
There was no difference in weight between any group (no steroid, deflazacort, prednisone), but deflazacort treated patients were significantly shorter than prednisone/no steroid patients. Authors discuss that it is clear steroid treatment should continue beyond loss of ambulation.
It slows down the upper arm, heart, and respiratory function. It also delays loss of important functions such as hand to mouth and turning in bed (important for patient autonomy and caregiver ‘burden’).
Authors outline the limitations of the study: the numbers were small (common with rare diseases), and there may have been confounders, e.g. deflazacort is more expensive than prednisone, so differences in socioeconomic status may have influenced disease progression as well.
Patients not receiving steroids, may also not receive other parts of the standards of care (e.g. less physiotherapy), which will also have an impact on disease progression. This is difficult to assess retrospectively.
Finally, the natural history study did not assess side effects of steroid use, so aside from height and weight which were captured, they cannot compare other common side effects of steroids such as osteoporosis, delayed puberty etc).
The paper has an important message (further evidence steroid use slows down disease progression in non-ambulant patients). I do not like how authors try to push for deflazacort over prednisone at some places. If they want to compare the two, they should compare daily to daily.
Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).
Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.
In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.