A group of leading lupus specialists has accused the 2025 American College of Rheumatology’s SLE treatment guidelines of pushing biologic therapies too far down the treatment ladder, potentially harming patients.
In a commentary published in Arthritis & Rheumatology [link here], nine rheumatologists from leading US and Canadian institutions argue the guidelines’ structure risks entrenching step-therapy barriers that delay access to newer, better-evidenced treatments.
Their central concern is sequencing. The ACR guidelines present biologics and conventional immunosuppressants as broadly equivalent options, without clearly specifying when earlier biologic use is warranted. The authors argue this is a step backwards from the 2023 EULAR update, which moved toward earlier biologic use in patients with persistent disease activity where glucocorticoid sparing is a priority.
“When guideline language does not clearly support earlier biologic use, payers often interpret that ambiguity as permission to require multiple rounds of conventional therapy before approving biologics,” the authors wrote.
The practical consequences, they argue, are serious: more cumulative glucocorticoid exposure, greater healthcare utilisation, delays in access and, in some cases, irreversible organ damage.
The commentary highlights what the authors describe as a fundamental paradox in current practice. Belimumab and anifrolumab were developed specifically for SLE, tested in robust clinical trial programs and evaluated through modern regulatory standards, and both have been shown to reduce organ damage accrual over standard of care. Yet many conventional immunosuppressants routinely used ahead of them were originally imported from transplant medicine or other autoimmune conditions, with far less direct evidence in lupus.
“This has produced an important paradox: in many health systems, patients must fail one or more unapproved, poorly studied medications before they can receive a treatment with regulatory approval and better evidence of efficacy,” the authors wrote.
The commentary identifies three further gaps in the guidelines.
On disease activity measurement, the authors acknowledge that the guidelines endorse regular assessment using validated instruments, consistent with a treat-to-target approach. But they argue the document stops short of identifying a practical standard for routine clinic use and offers no pathway to address electronic record limitations, provider burden or time constraints.
“A target that cannot be measured efficiently in clinic does not become standard care because it is conceptually attractive,” they wrote, calling for a feasible default instrument, a minimum dataset per visit and support for workflow integration.
The authors also take issue with the inclusion of agents such as quinacrine, lenalidomide and pentoxifylline in treatment pathways, arguing that while these drugs need not be excluded entirely, their role should be framed explicitly as selective and context-specific. As currently written, they warn, niche therapies “can be misread as mandatory waystations before access to newer targeted treatment is granted.”
A fourth concern is the near-absence of any mention of clinical trial referrals. With emerging data from CAR-T cell therapy, bispecific antibodies and new small molecules reshaping expectations for SLE treatment over the coming decade, the authors argue that formal acknowledgment of trial referrals would help normalise these discussions and connect patients more directly with innovation.
“Participation in well-designed clinical trials is not the last resort born of therapeutic exhaustion, but a legitimate component of modern SLE care in appropriately selected patients,” they wrote.
The commentary proposes three practical changes for future guideline iterations: clearer guidance on when earlier biologic use is favoured, treat-to-target recommendations paired with realistic implementation pathways, and explicit recognition of clinical trial referrals for refractory or high-risk disease.
“Lupus care has entered a period of meaningful therapeutic advancement,” the authors wrote. “Guidelines should reflect that momentum in a way that helps clinicians act earlier, measure better, and connect patients more directly with innovation.”