ACR 2025 SLE Treatment Guidelines: Key Organ-Specific Recommendations and Clinical Implications

The ACR 2025 SLE guideline shifts care to organ-specific therapeutic pathways for systemic lupus erythematosus, prioritizing organ threat and disease intensity over a one-size immunosuppressive approach.

The guideline replaces broad, disease-level algorithms with clear organ-based action points that translate vague escalation language into defined response windows and therapy ladders. Lupus nephritis, neuropsychiatric syndromes, and other major organ manifestations now have pathway-specific options and timing for escalation. Clinics should map these organ pathways into local protocols to ensure timely reassessment and rapid therapy changes.

Hydroxychloroquine is recommended for nearly all patients with SLE unless a clear contraindication exists, with a long-term target dose of 5 mg/kg/day to balance efficacy and retinal safety. This dose aligns with evidence linking lower weight‑adjusted daily dosing to reduced retinal toxicity while preserving protection against flares, damage accrual, and mortality. Baseline ophthalmology assessment is mandatory; routine screening cadence should be stratified by cumulative dose and duration, with annual exams standard after 5 years or earlier when dosing exceeds recommended thresholds. Implement weight‑based dosing and document ophthalmology follow-up to minimize harm and preserve benefit.

The guideline mandates early, aggressive escalation for organ‑threatening or refractory disease rather than prolonged reliance on inadequate initial regimens. For lupus nephritis, recommended steps include prompt induction with mycophenolic acid or cyclophosphamide, reassessment at 3 months for partial responders and at 6 months for complete response, and consideration of multiagent regimens or biologic therapy (eg, anti‑CD20 or targeted agents) when response milestones are not met.

For neuropsychiatric presentations, the guideline emphasizes immediate specialist involvement, an expedited diagnostic workup to distinguish inflammatory from noninflammatory causes, and a low threshold for intensified immunotherapy (pulse steroids ± cyclophosphamide or rituximab) when reversible inflammatory processes are suspected. These organ-specific escalation rules aim to avert irreversible damage by prioritizing timely intensification.

The guideline elevates multidisciplinary coordination and shared decision‑making as central to managing severe or complex SLE. Core team members include nephrology for renal disease, neurology and psychiatry for neuropsychiatric syndromes, ophthalmology for antimalarial surveillance, and obstetrics for pregnancy planning, with primary care and allied health as ongoing partners; composition varies with the organ involved. Shared decision‑making is operationalized through explicit discussion of risks and benefits, fertility and pregnancy planning when relevant, and incorporation of patient preferences into therapy choice and tapering.

Clinics should adopt specific referral triggers and regular MDT review for patients with major organ involvement to meet the guideline’s coordination expectations.

Forward impact will likely include faster, more targeted therapy changes, reduced cumulative steroid exposure, and improved prevention of irreversible organ damage.

Key Takeaways:

• An organ‑specific treatment framework replaces broader algorithms, with defined escalation windows and pathway‑specific options for major manifestations.
• All patients with active SLE are impacted, particularly those with lupus nephritis, neuropsychiatric disease, and other organ‑threatening presentations who now face earlier intensification.
• Clinics must implement weight‑based hydroxychloroquine dosing, formal ophthalmology screening protocols, defined reassessment timelines for organ disease, and MDT referral workflows.