Lupus Drug Withdrawal: Immunosuppressants or Steroids First?
In patients with systemic lupus erythematosus (SLE) who had been in remission for at least 1 year, immunosuppressant withdrawal was noninferior to glucocorticoid withdrawal, with no significant differences in the proportion of patients who experienced flares or in flare severity at 1- and 2-year follow-ups.
METHODOLOGY:
Researchers conducted a randomized noninferiority trial at a tertiary hospital in India (between May 2021 and December 2023) to compare the outcomes of immunosuppressant withdrawal with those of glucocorticoid withdrawal in adult patients with SLE in remission.
They included 117 patients with SLE who had received treatment for at least 3 years, had been in remission for at least 1 year, and were receiving glucocorticoids (≤ 7.5 mg/d of prednisolone) along with one maintenance immunosuppressant.
Patients were randomly assigned to one of the two groups: One tapered off prednisolone over 3 months while continuing immunosuppressants (n = 58; median age, 35 years; 98.3% women) and the other tapered off immunosuppressants while maintaining low-dose prednisolone (n = 59; median age, 36 years; 93.2% women). All patients continued receiving hydroxychloroquine.
The primary outcome was the proportion of patients who experienced a flare, as defined by the SELENA-SLEDAI Flare Index, at any time up to 52 weeks, with follow-up extending up to and beyond 104 weeks.
Noninferiority of immunosuppressant over glucocorticoid withdrawal was confirmed if the upper limit of the 95% CI for the between-group difference in the proportion of patients who experienced a flare was < 10%.
TAKEAWAY:
At 52 weeks and at maximum follow-up, the proportion of patients who experienced a flare did not differ significantly between the immunosuppressant and glucocorticoid withdrawal groups, with the risk difference between the groups indicating the noninferiority of immunosuppressant withdrawal.
At the maximum follow-up, 55.2% of patients in the glucocorticoid withdrawal group and 67.8% of those in the immunosuppressant withdrawal group did not experience a flare. Among those who did, mild to moderate flares were most common.
Damage accrual did not differ significantly between the two groups at maximum follow-up.
Low baseline complement C3 levels were identified as a predictor of flares at both 52 weeks (hazard ratio [HR], 3.698; P = .012) and at maximum follow-up (HR, 3.785; P = .001).
IN PRACTICE:
'Our results suggest that low-dose GCs [glucocorticoids], combined with HCQ [hydroxychloroquine], may be a viable long-term maintenance option for managing SLE patients in sustained remission,' the authors wrote. 'Based on our findings, it is evident that a one-size-fits-all approach to IS [immunosuppressant] or GC withdrawal may not be ideal. Instead, a personalized tapering approach considering patient risk profile, prior damage, and steroid exposure may help mitigate adverse events while maintaining disease control,' they added.
SOURCE:
This study was led by Aishwarya Gopal, MD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India. It was published online on March 24, 2025, in Rheumatology .
LIMITATIONS:
This study had an open-label design and lacked a control arm that continued all medications. Adrenal insufficiency upon flares was not tested in patients who underwent steroid withdrawal. Remote access to glucocorticoids could not be ruled out.
DISCLOSURES:
This study received funding from Jawaharlal Institute of Postgraduate Medical Education and Research. The authors declared having no conflicts of interest.
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