Comment on: “Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised controlled trial” by Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hie M, Pineton de Chambron M et al. Annals of the Rheumatic Diseases on-line first Dec 18 2019. Doi 10.1136/annrheumdis-2019-216303.
Commented by: Anisur Rahman, University College London, UK
It is widely accepted that using the minimum dose of corticosteroids to control disease activity in patients with systemic lupus erythematosus (SLE) is an important goal. This has been specified in Treat-to-Target guidelines for the management of SLE (1) and is especially important because corticosteroids are an important cause of damage in these patients, notably cataract and osteoporotic fractures.
One way to reduce use of corticosteroids in patients with SLE would be to withdraw them altogether in patients whose disease is quiescent. Both physician and patient, however, may be reluctant to do this because of the fear that a flare of disease may result.
This study (CORTICOLUP – NCT 02558517), carried out at a single centre in Paris, France was a prospective randomised trial to compare the onset of flare in patient who either had prednisone dose maintained at 5mg per day or withdrawn.
The study was carried out between 2014-7. Patients were eligible for inclusion if they had SLE that had been quiescent for at least one year (i.e. SLEDAI-2K score < 4, no BILAG B or A in any organ and a PGA = 0) AND were on a stable drug regime for SLE that included prednisone 5mg per day. Of 124 patients who were included, 61 were randomised to continue prednisone 5mg per day whereas 63 were randomised to withdrawal of prednisone. Prednisone was stopped completely on day 0 (not tapered) but 20mg per day hydrocortisone was given for the first month to avoid adrenal failure. There was no loss to follow-up over a one-year period. Only two patients in the group that were randomised to continue prednisolone stopped it (for personal reasons) during the follow-up and conversely only four who had withdrawn from prednisolone re-started it (two due to pregnancy).
The two treatment groups were well-matched in terms of duration of SLE, duration of remission, previous renal involvement, anti-DNA, damage, low C3 level and use of hydroxychloroquine and immunosuppressants.
The primary outcome measure was the number of patients who had flares, as defined by the revised SELENA-SLEDAI flare index (rSFI). This outcome measure clearly favoured the group that continued 5mg prednisone per day, who had 4 flares (1 severe) as opposed to 17 flares (5 severe) in the prednisone-withdrawal group (RR 0.2, 95% CI 0.1-0.7 p = 0.003).
The authors list a range of secondary outcome measures related to disease flare that were also better in the prednisone maintenance group. The groups did not differ, however, in terms of increase in damage index score or adverse events.
This paper suggests that, at least in this group of patients, it will be difficult to withdraw corticosteroids without a high risk of causing a flare of disease – withdrawal increased the risk of flare by five-fold. Of note, these were patients in long-term remission. Although the inclusion criteria only required 12 months of remission, most patients had been in remission for far longer – mean (SD) duration of remission was 55.7 (5.8) months in the maintenance group and 67.5 (6.8) months in the withdrawal group.
In summary, this was a well-designed study that came to a clear conclusion about the benefit of continuing low-dose corticosteroid in patients with quiescent SLE. The authors mention as a limitation the possibility that a slower taper of prednisone dosage might have led to fewer flares. It will be important to repeat this type of study in other populations – though the patients seen at this hospital are known to be ethnically diverse.
- Van Vollenhoven RF et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Annals of the Rheumatic Diseases 73; 958-67 (2014)