Phase 3 Results Suggest Low-Dose Prednisone Lowers Flare Risk in SLE Patients in Remission
People with systemic lupus erythematosus (SLE) who have been in remission for at least a year and take low-dose prednisone as maintenance therapy have less risk of a disease relapse than those who stop taking it, a recent study suggests.
The study, “Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial,” was published in the Annals of the Rheumatic Diseases.
SLE is characterized by a fluctuating course, with patients experiencing flares that require medical attention and lead to a loss of work productivity. Active disease is often treated with glucocorticoids, but little information is available on the effects of glucocorticoid withdrawal once patients achieve stable remission.
While long-term administration of glucocorticoids is often avoided due to their known toxicity, physicians often prefer to continue with a low-dose of them, even in clinical remission particularly when there is history of major organ involvement.
To further investigate the effects of glucocorticoids in SLE patients who had achieved remission, researchers conducted a randomized Phase 3 clinical trial (NCT02558517) called CORTICOLUP. This single-center, one-year trial compared maintenance versus withdrawal of a 5-mg-per-day dose of prednisone to prevent flares.
The trial enrolled 124 patients with clinically inactive disease during the prior year as well as stable treatment for at least the same period with 5 mg/day prednisone. Of these, 61 continued on prednisone and 63 stopped it. Those stopping treatment with prednisone were given 20 mg/day of hydrocortisone over one month to prevent adrenal failure.
The study’s primary goal was the occurrence of flares at one year, assessed with the SELENA-SLEDAI flare index (SFI). Secondary goals included the severity of flares, according to SFI and the British Isles Lupus Assessment Group index, time to flare and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index.
Results showed that significantly more patients in the withdrawal group (17 patients, 27%) experienced a flare at one year compared with those continuing on low-dose prednisone (four patients, 7%).
Those who maintained treatment had a significantly lower proportion of mild/moderate flares and a lower, although not significant, proportion of severe flares than the withdrawal group.
Among patients still on prednisone, flares included four cases of arthritis, two skin manifestations, and one case of lupus nephritis. Three of these flares were treated with an increased dose of prednisone and one flare was treated with an immunosuppressant therapy.
In the withdrawal group, flares included 12 cases of arthritis, seven skin manifestations, and two cases of lupus nephritis. Treatments included increased prednisone dosing for 12 flares and a new immunosuppressant or immunomodulatory therapy for four flares.
Three patients in the withdrawal group experienced damage-related manifestations, including two osteoporosis-related fractures, one retinal (eye) toxicity due to antimalarials, and one cataract. No patient in the maintenance group experienced such complications.
However, the researchers could not find a statistically significant benefit with maintenance therapy on reducing damage. Still, “the reduction in the number of flares with the maintenance of prednisone at low doses is clearly important because previous reports have shown a strong link between the number of flares and the damage accrual, as well as the quality of life,” they wrote.
Despite not observing substantial harm from using low-dose prednisone (in contrast with previous research), the limited number of patients and follow-up duration do not allow meaningful conclusions from this study.
Overall, the researchers believe their study presents the strongest evidence to date of a beneficial effect of low-dose prednisone over withdrawal, in the context of flare prevention in SLE patients in remission.
“These results must be validated in other independent cohorts and larger studies must be undertaken to determine whether clinical characteristics and new biomarkers … could help clinicians to identify a subgroup of SLE patients clinically in remission but who are at higher risk of relapse and who would benefit from a continued intake of low doses of prednisone,” they wrote.