Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Immunosuppressant Withdrawal is Non-Inferior to Glucocorticoid Withdrawal in Systemic Lupus Erythematosus: 2-Year Outcomes of a Randomized Controlled Trial
Background: Current recommendations in Systemic Lupus Erythematosus (SLE) suggest stopping glucocorticoids (GCs) and continuing hydroxychloroquine (HCQ) and immunosuppressive (IS) agents once long-term remission is achieved. It remains unclear if IS withdrawal is non-inferior to GC withdrawal. We hypothesized that IS withdrawal is non-inferior to GC withdrawal in patients with SLE in clinical remission.
Methods: In this open-label, single-center, randomized controlled trial, we compared the occurrence of flare in stable SLE patients where GC or IS were tapered. SLE patients >18 years on stable GC dose (prednisolone ≤7·5 mg/day), and on maintenance non-biological IS for ≥3 years, who are in clinical remission for ≥1 year were enrolled and assigned to either taper GC or IS over 3 months. The primary endpoint was the proportion of patients experiencing a flare defined by the SELENA-SLEDAI Flare Index (SFI) at 52 weeks. Those in remission beyond 52 weeks were followed up to the maximum available follow up duration after 104 weeks and the outcomes are reported here. The trial was registered with CTRI/2020/07/026712.
Findings: Patients were recruited between May 2021 and December 2021. Among 121 patients randomized, 117 (GC withdrawal, n=58; IS withdrawal, n=59) were included in the primary analysis. Flare occurred in 31% patients in the GC withdrawal group and 20·3% in the IS withdrawal group (risk difference, 10·6% [95% CI, −26·5 to 5·1]; p=0·18), demonstrating the noninferiority of IS withdrawal. At maximum follow up, 44.8% in the GC withdrawal group and 32·2% in the IS withdrawal group experienced a flare (risk difference, −12·6% [95% CI, −30·1 to 4·9]; p=0·11), confirming the noninferiority of IS withdrawal at 2 years. Infections and damage-related adverse events were more frequent in the IS withdrawal group.
Interpretation: IS withdrawal is noninferior to GC withdrawal in SLE patients who are in long-term clinical remission. Personalized tapering strategies based on baseline damage and steroid exposure may optimize outcomes.
Trial Registration: The trial was registered with CTRI/2020/07/026712.
Funding: The study was funded intramurally by Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) (JIP/Res/intramural/subcom/2020-2021).
Declaration of Interest: The authors declare no conflicts of interest.
Ethical Approval: The trial protocol and its subsequent revisions were reviewed and approved by the institutional ethics committee.
Keywords: Drug withdrawal, remission, SLE, glucocorticoids, immunosuppressant, noninferiority, flare
Gopal, Aishwarya and Chengappa, Kavadichanda G and Mariaselvam, Christina and Harichandrakumar, KT and Thabah, Molly and Negi, Vir Singh, Immunosuppressant Withdrawal is Non-Inferior to Glucocorticoid Withdrawal in Systemic Lupus Erythematosus: 2-Year Outcomes of a Randomized Controlled Trial. Available at SSRN: https://ssrn.com/abstract=5038432 or http://dx.doi.org/10.2139/ssrn.5038432
Download This Paper