ACR Releases New Guideline for Management of SLE at ACR 2025

CHICAGO—At ACR Convergence 2025, the new 2025 ACR Guideline for the Treatment of Systemic Lupus Erythematosus (SLE) was unveiled.¹

Guideline Development & Key Recommendations

Dr. Sammaritano

Lisa Sammaritano, MD, professor of clinical medicine at Weill Cornell Medical College and the Hospital for Special Surgery, New York, kicked off the session by explaining the guideline development process.

The guideline was last published in 1999, and lupus treatment has significantly evolved since that time, including the introduction of new biologic therapies, belimumab and anifrolumab, approved by the U.S. Food & Drug Administration (FDA).

The process involved scoping articles, developing 52 broad PICO [patient/population/problem, intervention, comparison, outcome] clinical questions, conducting a literature review (over 10,000 articles reviewed with 63 references selected) and evaluating the evidence using the GRADE (grading of recommendations assessment, development and evaluation) process.

“Recommendations were listed as strong or conditional, based on the level of evidence and certainty that benefits outweigh harms,” Dr. Sammaritano said. “There was also input from a patient panel discussion.”

Some limitations in scope included not addressing recommendations for diagnosis of SLE or broader, less well-understood issues, such as type 2 SLE, mental health and SLE-associated comorbidities, including bone health, cardiovascular disease or malignancy screening.

“For glucocorticoids, we urge prompt use to obtain rapid control of inflammation using the lowest dose for the shortest duration, and tapering as soon as possible to limit toxicity,” Dr. Sammaritano stated.

Dosages for hydroxychloroquine (HCQ) were also discussed. “All patients should be treated with hydroxychloroquine, unless contraindicated, and continued indefinitely even if in sustained remission,” Dr. Sammaritano said. Although the long-term goal is to maintain a daily dose of less than or equal to 5 mg/kg, the guideline notes short courses of higher doses of hydroxychloroquine (5–6.5 mg/kg/day) may be necessary at initiation of treatment to maintain disease control or during pregnancy.

All organ-specific recommendations were noted to be conditional.

Treating Lupus Serositis

Dr. Duarte-Garcia

Ali Duarte-Garcia, MD, MSc, assistant professor of medicine at the Mayo Clinic College of Medicine and Science, Rochester, Minn., discussed how to apply the guideline to treat lupus serositis. Lupus serositis refers to inflammation of serosal membranes, including pleuritis and pericarditis. Up to 43% of patients experience pleuritis during their disease course.²

For pleuropericarditis, the guideline conditionally recommends initial treatment with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine or their combination, with a low threshold to escalate to glucocorticoids, over initiating with steroids alone.

“Glucocorticoids may still be needed in SLE pericarditis,” Dr. Duarte-Garcia said. “For example, they may have other concomitant systemic disease activity, contraindication to NSAIDs, drug interactions or symptoms unresponsive to NSAIDs and colchicine.”

For ongoing/recurrent pleuropericarditis despite NSAIDs, colchicine and/or glucocorticoids, conventional immunosuppressants or biologic therapies are recommended over initiating or increasing glucocorticoid monotherapy.

“The voting panel’s preferred biologic therapy for predominant pleuropericarditis is IL-1 [interleukin-1] blockade,” Dr. Duarte-Garcia said. “This had low level of evidence but was backed by consensus and experience of the Voting Panel.”

He presented a randomized, controlled trial of azathioprine (AZA) vs. mycophenolic acid analog (MPAA) in 240 patients with SLE of which 70 had serositis. The trial demonstrated no statistically significant difference but trend to MPAA (with numerical benefit of MPAA in serositis compared with AZA).³

Pooled analysis of belimumab trials (BLISS-52 and BLISS-76) demonstrated numerical benefit for belimumab in SLE serositis, although underpowered for significance, Dr. Duarte-Garcia explained.⁴ Similarly, pooled analysis from TULIP-1 and TULIP-2 for anifrolumab favored active drug, although underpowered for significance.⁵ Lastly, a meta-analysis of observational studies and randomized, controlled trials in recurrent pericarditis demonstrated improvement in patients who received IL-1 blockade compared with placebo or standard of care, but patients with SLE were excluded from most of these studies.⁶

Treating Cutaneous Lupus

Dr. Werth

Victoria Werth, MD, professor of dermatology at the University of Pennsylvania and chief of dermatology at the Corporal Michael J. Crescenz VA Medical Center, Philadelphia, spoke on the guideline recommendations for cutaneous lupus.

“Skin involvement is present in up to 70–80% of patients with SLE,” Dr. Werth said. “These patients have lower quality of life, and early treatment is critical to minimize damage.”

For sunscreen, the recommendation is to block both UVB and UVA, with SPF 70 or higher recommended for chemical sunscreens and SPF 50 or higher for physical-based sunscreens, Dr. Werth reviewed.

The cutaneous lupus erythematosus (CLE) category combines acute, subacute and chronic cutaneous lupus erythematosus. Initial therapy for cutaneous lupus rash includes hydroxychloroquine, topical glucocorticoids and/or calcineurin inhibitors, and intralesional steroids and/or brief course of oral glucocorticoids.

For mild CLE that is ongoing despite treatment with hydroxychloroquine and/or topical therapies, the guideline conditionally recommends adding quinacrine or switching to chloroquine, over adding an immunosuppressive agent. “Quinacrine is available through compounding pharmacies and not associated with increased retinopathy risk,” Dr. Werth noted. “In contrast, chloroquine has a higher risk for retinal toxicity and requires visual fields every four to six months.”

For ongoing moderate-severe cutaneous lupus refractory to topical and antimalarial therapies and/or oral glucocorticoid necessitating escalation of therapy, the guideline conditionally recommends the addition of methotrexate (MTX), MPAA, anifrolumab and/or belimumab. “Choice of specific therapy should be based on severity of lesions, the risk for scarring, comorbidities and patient preference,” Dr. Werth said. Given limited data and difference of opinion among panel members, no prioritization of specific agents was made.

For moderate-severe refractory cutaneous lupus that fails all other therapies discussed, the guideline recommends adding or substituting lenalidomide.

For mild ongoing bullous lupus, despite topical and antimalarial therapies, dapsone is recommended over glucocorticoid. For moderate-severe bullous lupus refractory to therapy, a conventional immunosuppressive (MPAA, methotrexate, azathioprine) and/or anti-CD20 therapy is recommended.

For chilblain lupus, despite topical and antimalarial therapies, the guideline recommends the addition of pentoxifylline, PDE5 inhibitors (e.g., sildenafil) and/or calcium channel blockers, over immunosuppressive therapies.

For mild cutaneous vasculitis, despite topical and antimalarial therapies, the guideline recommends the addition of dapsone or colchicine over immunosuppressive therapies.

Treating Lupus Arthritis

Dr. Askanase

Anca Askanase, MD, professor of medicine at Columbia University School of Medicine, New York, next presented on applying the guideline to treating arthritis. “Joint involvement occurs in up to 95% of SLE patients,” Dr. Askanase said. “It can result in permanent joint damage or deformity, lower quality of life and work disability.”

For acute or recurrent episodes of inflammatory arthritis, the guideline recommends a course of NSAIDs or limited course of oral glucocorticoids. For patients who have persistent or recurrent active SLE arthritis and are taking HCQ, the guideline recommends initial therapy with MTX, MPAA or AZA, with low threshold to add or substitute with belimumab or anifrolumab for inadequate response, over initial biologic therapy.

Additional conditional recommendations were provided, such as considering initial biologic therapy for refractory arthritis or combination therapy (conventional disease-modifying anti-rheumatic drug plus biologic). For predominant arthritis without other organ involvement, MTX can be considered first. For other organ involvement, MPAA might be preferable. For those planning pregnancy, azathioprine is preferred.

“When arthritis is the predominant feature, leflunomide or other therapies approved for rheumatoid arthritis [RA] could be used,” Dr. Askanase said. “Baricitinib has moderate evidence supporting its benefit. There is also limited evidence supporting benefit for abatacept, tocilizumab, tofacitinib and ustekinumab.”

For Jaccoud arthropathy, no consensus was reached on surgical or medical therapy. Referral to occupational therapy/physical therapy, splinting or bracing were suggested.

Data from post-hoc analyses of randomized, controlled trials of belimumab and anifrolumab were presented, demonstrating improvement in lupus arthritis.^4,7-12

Treating Childhood Onset Lupus

Dr. Hiraki

Linda Hiraki, MD, FRCPC, ScD, associate professor at The Hospital for Sick Children, Toronto, and Bonnie Bermas, MD, professor of medicine at University of Texas Southwestern at Dallas, presented on applying the ACR Guideline to children and adolescents with SLE.

“These guidelines were meant to be applicable for people with SLE across the lifespan and are not restricted to a specific age,” Dr. Hiraki said. “However, there are specific pediatric considerations.”

The guideline recommends that a pediatric rheumatologist should be consulted in pediatric SLE, when possible, especially in highly complex or acutely ill patients.

“Youth with childhood SLE should be monitored for delayed pubertal onset and growth velocity, due to disease activity and glucocorticoid treatment,” Dr. Hiraki said. “In addition to close monitoring and partnering with endocrinology when necessary, applying pediatric-specific glucocorticoid dosing is also recommended.”

Depression, anxiety and suicidal ideation are common among adolescents and young adults with cSLE, and should be considered in evaluating these patients.^13,14 The ACR Guidance Statements for Addressing Mental Health Concerns in Youth With Pediatric Rheumatologic Diseases can be a helpful resource to reference, Dr. Hiraki said.¹⁴

Transition to Adult Care

Dr. Bermas

A planned transition to adult care is recommended to decrease risks of unscheduled healthcare use, care gaps and disease flares, Dr. Hiraki explained.

“The transition to adult care should ideally start many years before the adolescent turns 18,” Dr. Bermas reiterated. This process includes assessing skills for transition readiness, conducting a self-care assessment, developing a transition plan and providing transfer documents, as well as communicating to the adult provider.¹⁵

Dr. Bermas noted the importance of adult rheumatologists to assess self-efficacy in patients transitioning to adult care, as well as address such concerns as fertility, contraception, bone health and mood.

Q&A

In the Q&A session, Dr. Sammaritano explained no specific recommendations provided for use of hydroxychloroquine levels, due to limited evidence and variable testing from institution to institution. This was noted to be an area of great interest, however, and was highlighted as a future research goal.

Another audience member asked about the use of tumor necrosis factor (TNF) inhibitor in SLE arthritis. “There are case series of use of TNFi in SLE arthritis, especially in cases with RA-like overlap or erosive disease,” Dr. Askanase said. “I think it makes sense to use in situations. However, there is a concern for possible exacerbation of lupus symptoms from TNF inhibitor therapy.”

One audience member asked about the mention of IL-1 inhibition without specific data of its efficacy in SLE pericarditis. “Clinicians seek practical guidance, even when it must rely on expert consensus or case series in the absence of clinical trials or high-quality evidence,” Dr. Duarte-Garcia responded.

Mithu Maheswaranathan, MD, is an assis­tant professor of medicine in the Division of Rheumatology at Duke University School of Medicine, Durham, N.C. and can be followed on X/Twitter @MithuRheum.

References

1. Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) guideline for the treatment of systemic lupus erythematosus. https://rheumatology.org/lupus-guideline.
2. Ryu S, Fu W, Petri MA. Associates and predictors of pleurisy or pericarditis in SLE. Lupus Sci Med. 2017 Oct 23;4(1):e000221.
3. Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M, et al. Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: A randomised clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1575–1582.
4. Manzi S, Sánchez-Guerrero J, Merrill JT, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: Combined results from two phase III trials. Ann Rheum Dis. 2012 Nov;71(11):1833–1838.
5. Morand EF, Furie RA, Bruce IN, et al. Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythematosus: A post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials. Lancet Rheumatol. 2022 Apr;4(4):e282–e292.
6. Imazio M, Andreis A, Piroli F, et al. Anti-interleukin 1 agents for the treatment of recurrent pericarditis: A systematic review and meta-analysis. Heart. 2021 Jul 12;107(15):1240–1245.
7. Fanouriakis A, Adamichou C, Koutsoviti S, et al. Low disease activity-irrespective of serologic status at baseline-associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study. Semin Arthritis Rheum. 2018 Dec;48(3):467–474.
8. Iaccarino L, Bettio S, Reggia R, et al. Effects of belimumab on flare rate and expected damage progression in patients with active systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2017 Jan;69(1):115–123.
9. Merrill JT, Furie R, Werth VP, et al. Anifrolumab effects on rash and arthritis: Impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. Lupus Sci Med. 2018 Nov 26;5(1):e000284.
10. Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): A randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019 Dec;1(4):e208–e219.
11. Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020 Jan 16;382(3):211–221.
12. Tanaka Y, Tummala R. Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: An overview from clinical trials. Mod Rheumatol. 2021 Jan;31(1):1–12.
13. Rubinstein TB, Dionizovik-Dimanovski M, Davis AM, et al. Multicenter study of utility and acceptability of depression and anxiety screening in adolescents and young adults with childhood-onset systemic lupus. Arthritis Care Res (Hoboken). 2023 Apr;75(4):724–733.
14. Cunningham NR, Danguecan AN, Ely SL, et al. American College of Rheumatology guidance statements for addressing mental health concerns in youth with pediatric rheumatologic diseases. Arthritis Care Res (Hoboken). 2025 Aug;77(8):953–964.
15. White PH, Ardoin S. Transitioning wisely: Improving the connection from pediatric to adult health care. Arthritis Rheumatol. 2016 Apr;68(4):789–794.