Younger Age Deemed Risk Factor of Flare in Patients Discontinuing Glucocorticoids

Patients with systemic lupus erythematosus (SLE) who discontinued glucocorticoids (GCs) were at a higher risk of flare if they were younger in age or were serologically active yet clinically quiescent (SACQ), according to a study published in Lupus Science & Medicine.¹ Hydroxychloroquine may help to prevent these flares.

“GCs have been the cornerstone in the treatment of SLE, irrespective of immunosuppressive agents or biological therapy. Nevertheless, prolonged use of GC may cause irreversible organ damage, leading to impaired quality of life and even increased mortality,” investigators explained. “Therefore, it is still worthy trying to discontinue GC in patients with SLE, but careful selection of candidates to GC withdrawal is mandatory.”

Investigators utilized Medline/PubMed, Cochrane Library, EMBASE, and Scopus databases dated from the archive’s establishment up to July 9, 2021 to identify studies examining relapses and flares in patients with SLE after ending GC treatment. Two investigators evaluated the results using a predefined grid. Data included the year of publication, country of origin, authors, data source, study design, sample size, demographics and clinical characteristics, and outcomes. Pooled risk ration (OR) was calculated with 95% CIs and risk estimates were adjusted.

Inclusion criteria is listed below:

Nine studies analyzing 635 patients were included in the analysis. A total of 99.5% (n = 632) of patients were in remission before the decision to withdrawal from GCs. Mean disease duration ranged from 48 to 188 months and mean remission duration ranged between 3 and 68 months.

There was an association between SACQ and an increased risk of flare (pooled OR=1.78; 95% CI 1.00 to 3.15) in 4 studies, including 385 patients with SLE. The median quality score was 7.5.

Older patients had slightly fewer flares after withdrawing from GCs, as assessed in 5 studies, when compared with younger patients (weighted mean difference [WMD] −2.04, 95% CI [−4.15 to 0.06]). Of the 371 patients included, 22.9% (n = 85) experienced a flare after GC withdrawal. The mean age was between 29 and 39 years.

Sex, disease and remission duration, immunosuppressants, and GC treatment duration did not impact risk of flare. Additionally, there was no correlation between lupus nephritis (LN) and flare (pooled OR 1.20; 95% CI 0.55 to 2.64) or neuropsychiatric (NP)-SLE and flare (pooled OR 0.95; 95% CI 0.50 to 1.83).

Concomitant HCQ usage was shown to slightly decrease flare risk in this patient population (pooled OR 0.50; 95% CI 0.23 to 1.07), as shown in 5 studies analyzing 448 patients.

Insufficient data on other risk factors for flare limited the study by inhibiting subgroup evaluations. Although both RCT and cohort studies were included, there is a potential for bias as only a few studies allowed for subanalysis. Further, Statistical significance could not be confirmed in results with CI included. Investigators would like to conduct studies with larger sample sizes in the future.

“This study showed an increased risk of flare among patients with SLE with SACQ after GC withdrawal,” investigators concluded. “A new era without GC in the treatment of SLE needs introducing novel therapies and biomarkers.”

Reference:

Ji L, Xie W, Fasano S, Zhang Z. Risk factors of flare in patients with systemic lupus erythematosus after glucocorticoids withdrawal. A systematic review and meta-analysis. Lupus Sci Med. 2022;9(1):e000603. doi:10.1136/lupus-2021-000603