Findings in Phase 2 trial of prednisolone seen as inconclusive due to pandemic by Patricia Inácio, PhD from Scleroderma News
Moderate doses of oral prednisolone, a corticosteroid, given for a short period may help to ease symptoms in people with early diffuse cutaneous scleroderma (dcSSc), a Phase 2 trial suggests.
The study, intended to assess whether moderate dose of corticosteroids are safe and effective for early dcSSc, was affected by the COVID-19 pandemic starting in March 2020 and failed to provide conclusive results, its researchers noted.
Given the disease’s “inflammatory basis,” however, its findings may provide “support for the view of many clinicians that it is not unreasonable to prescribe short-term moderate dose prednisolone for symptom control, always remembering the importance of careful monitoring of blood pressure and renal function,” the team wrote.
The study, “A Phase II randomised controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS)” was published in the journal Rheumatology.
Prednisolone use ‘contentious’ due to risk of renal crisis with dcSSc
Scleroderma, also known as systemic sclerosis (SSc), is marked by progressive scarring in the skin and, possibly, internal organs that include the kidneys. The disease is caused by a wrongful immune response against the body’s own proteins.
Organ damage is a particular risk for people with dcSSc, and one that develops early in the disease’s course and can worsen quickly. Currently, no effective disease modifying treatments are available for these patients.
Although the inflammatory basis of dcSSC supports the use of corticosteroids, their use poses of risk of a renal, or kidney, crisis.
“Whether or not they should be prescribed is therefore highly contentious,” the researchers wrote.
Scientists in the U.K. designed the Phase 2 PRednisolone in early diffuse SSc (PRedSS) trial (NCT03708718) to assess the safety and effectiveness of prednisolone at a moderate dose compared to a placebo in adults with early dcSSc. The study was funded by Versus Arthritis.
Adults with early dcSSc, defined as onset within three years of skin thickening, were being recruited across 14 U.K. centers starting in December 2017 and randomly assigned to a daily capsule of prednisolone at 5 mg or a placebo when the pandemic took hold. The study, which continued recruiting through January 2021, then moved from a double-blinded to an open-label design, meaning all were aware of what they were being given. Placebo was halted and people in that group continued only with their background therapies as controls.
Of the 35 adult patients enrolled — out of a targeted 72 participants, with 10 entering in the open-label phase — 17 were on active treatment (mean age of 52.7, seven men) and 18 (mean age of 55.3, nine men) were initially on placebo and later on “no treatment.” Active treatment continued as a daily enteric-coated oral capsule of prednisolone at 5 mg; enteric-coated capsules prevent the medication from being dissolved in the stomach.
Prednisolone was given for six months, during which a proton pump inhibitor, as well as calcium and vitamin D supplements also were prescribed. In the case of adverse events deemed likely linked to prednisolone, its dose could be reduced.
The main goal was to assess changes in functional ability, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), and in skin thickness, assessed by the modified Rodnan skin score (mRSS), after three months of treatment.
Changes favored treatment, but trial’s main goals were not reached
At three months, results showed a small difference favoring prednisolone in HAQ-DI and mRSS scores, but they were not statistically significant.
“The assessment of the mRSS was hampered with the move away from face-to-face follow-up assessments necessitated by the COVID-19 pandemic,” the study noted.
Secondary goals included changes with treatment in pain, anxiety and helplessness, assessed using a subscale of the Rheumatology Attitudes Index.
Results here showed significantly less pain, anxiety and helplessness with prednisolone’s use. A trend also was seen for better skin-related quality of life with prednisolone, as assessed by the SSc Skin Patient-reported Outcome.
At least one adverse event was reported in 15 patients, and serious adverse events were noted in control group participants, including a heart attack and pulmonary arterial hypertension. In the prednisolone group, there were two cases of new-onset hypertension or high blood pressure.
No cases of scleroderma renal crisis were reported, and treatment “appeared safe,” the researchers wrote. But “patient numbers were small and it is also possible that longer durations of prednisolone therapy might increase renal crisis risk,” they added.
The study was stopped early due to the COVID-19 pandemic, rendering its findings inconclusive.
“Although PredSS has not provided a definitive answer as to whether or not corticosteroids should be prescribed in patients with early dcSSc, it provides critical insights for future studies addressing this important clinical question,” the researchers concluded.
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