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VIENNA — Glucocorticoid discontinuation is possible without increasing flare risk, if tapered slowly and carefully, in patients with systemic lupus erythematosus (SLE) in stable remission.

In presentations at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, new data on the benefits and risks of tapering and the risk for flare on discontinuation of glucocorticoids in SLE were addressed by speakers with a special interest in this aspect of care.

The presenters discussed progressive tapering and discontinuation of glucocorticoids to minimize long-term adverse effects as "a crucial aspect of management" of treat-to-target strategies.

Filippo Vesentini, MD, of the University of Padua, Padua, Italy, presented a retrospective analysis of prospectively collected data that compared the risk for flare (defined as any rise in clinical SLE Disease Activity Index-2K > 0 or the need for changes in SLE medications) during remission with glucocorticoid discontinuation vs low-dose maintenance glucocorticoids at ≤ 5 mg/d.

"In SLE patients in stable remission of at least 2 years, especially those with normal complement levels and in therapy with hydroxychloroquine, glucocorticoid withdrawal after gradual tapering is feasible and seems to be safe," Vesentini told Medscape Medical News.

Of 484 patients who reached remission, 360 discontinued glucocorticoids over a mean of 25.2 months, and 124 continued low-dose maintenance glucocorticoids.

Patients who had come off glucocorticoids experienced 48 flares vs 37 flares in those who remained on glucocorticoids over a mean follow-up of just over 7 years. These corresponded to annual flare rates of 1.65 and 8.5 flares per 100 patients per year, respectively. The last remission of those off glucocorticoids lasted a mean of 103 months vs 42 months in those still on them.

Vesentini also reported results that shed light on risk factors for flare on glucocorticoid discontinuation. Using serologic results, "we found that high complement C3 levels were protective for flare with a hazard ratio (HR) for flare of 0.029 (95% CI, 0.006-0.140; P < .001), and for every 1 mg of C3 level increase, the risk for flare reduced by 2.9%," he reported.

He also found that the presence of positive anti-U1RNP antibodies (HR, 1.973; 95% CI, 0.998-3.940; P = .054), thrombocytopenia (HR, 2.446; 95% CI, 1.106-5.410; P = .027), and vasculitis (HR, 3.033; 95% Cl, 1.262-7.432; P = .013) were negative predictors for being flare-free in patients in remission, again when off glucocorticoids.

However, disease duration positively predicted flare-free remission with an HR of 0.943 (95% CI, 0.892-0.998; P = .05), Vesentini reported.

Sarah Dyball, MD, rheumatologist and MRC Clinical Research Fellow in Clinical Pharmacology and Therapeutics, at The University of Manchester, Manchester, England, co-moderated the session. She told Medscape Medical News that, "These results reinforce the message to minimize steroid prescribing where possible, but there should be a personalized assessment of benefit and risk of steroids to minimize risk of flare and damage," she remarked.

Dyball added that, "The efforts by SLICC [Systemic Lupus Erythematosus International Collaborating Clinics] to develop an updated damage index will be pivotal in furthering research into minimizing damage associated with steroid use."

Attempt Glucocorticoid Tapering Very Slowly

Murray B. Urowitz, MD, professor of medicine at the University of Toronto and director of the Centre for Prognosis Studies in the Rheumatic Diseases and the Lupus Clinic at Toronto Western Hospital in Toronto, Ontario, Canada, discussed when and how to taper glucocorticoids in SLE at EULAR 2024.

Essentially, based on his own study data, he suggested that starting on a higher initial prednisone dose, followed by very slow dose reduction after 6 months, will help avoid damage accrual.

He referred to the 2023 EULAR recommendations for the management of SLE, which said that the glucocorticoid dose should be based on the type and severity of organ involvement and reduced to a maintenance dose of ≤ 5 mg/d (prednisone equivalent) as quickly as possible, and when appropriate, withdrawn entirely.

"Ideally, one could envision the use of glucocorticoids only as 'bridging therapy' in SLE and complete withdrawal is the optimal target," he remarked.

Urowitz noted that EULAR was much more "introspective" in its advice for reducing glucocorticoids in lupus nephritis. "In 3 months, you might get to 25% reduction in urine protein, while in 6 months, this might reduce to 50%, and at 24 months or longer, you might reach 500-700 mg protein over 24 hours. This is a very slow reduction after an initial high dose [of glucocorticoids]."

Referring to data from a study he coauthored in 2021, Urowitz pointed out that higher initial prednisone doses, such as 40 mg/d for approximately 6 months, achieved significantly better rates of complete renal response at 12 months in new-onset lupus nephritis.

"These patients received less cumulative glucocorticoids in the second and third year and did not accrue more glucocorticoid-related damage," he said, stressing that, "you're only giving a higher dose for a short period of time, but it was enough to get complete remission over 2-3 years.

"The findings suggest that treatment of lupus nephritis with initially high doses of prednisone leads to improved rates of renal response that may allow for faster glucocorticoid tapering compared to patients who were treated with lower doses."

Turning to when and how to discontinue glucocorticoids, Urowitz referred to a recent study (CORTICOLUP) showing that abrupt glucocorticoid withdrawal increased the likelihood of flare in the next year. In contrast, he then discussed retrospective study findings related to clinical flare rates and damage accrual in patients who tapered glucocorticoids gradually after prolonged clinical remission for a continuous period of 2 years for the first time during a patient's disease course.

The study compared low maintenance dose and discontinuation slowly over 2 years in SLE. Flares at 12 and 24 months and 24-month damage accrual were recorded.

Urowitz reported that "gradual glucocorticoid withdrawal was not associated with significantly increased risk for clinical flares at 12 and 24 months (increase in clinical SLEDAI-2K > 4 was 26.5% with low-dose maintenance vs 12.7% with discontinuation, respectively)."

Damage accrual occurred in a significantly lower percentage of withdrawal patients at 24 months compared with low-dose maintenance (17.6% vs 6.9%). "Those who kept their steroids over 2 years had significantly more damage than those who were weaned," he said. "Not only is there the beneficial effect of no flares but there's the extra benefit of knowing there's reduced damage over time.

"So, because gradual withdrawal was not associated with significant clinical flares and less damage accrual, gradual glucocorticoid withdrawal is safe in clinically quiescent SLE and should be attempted to reduce further damage accrual," Urowitz concluded.

Vesentini, Urowitz, and Dyball had no relevant financial relationships with industry to report.