Background/Purpose: Clinicians prescribing biologics must be aware of the expanding indications for biologic/systemic therapies across dermatology and rheumatology alike. Given disease-state overlap between these fields, providers should also recognize relevant medical indications beyond their specialty. There is growing evidence supporting biologic off-label use in conditions such as spondyloarthritis and systemic lupus erythematosus (SLE). This systematic review aims to guide clinicians in determining biologic and systemic therapies for patients with co-occurring dermatologic and rheumatologic conditions by summarizing available evidence on overlapping indications.

Methods: A systematic search of PubMed & Scopus databases from inception through March 2025 was conducted using the following format: (((BiologicName treat*[Title/Abstract] OR (BiologicName improve*[Title/Abstract])) NOT (Skin Diseases, Infectious[MeSH Terms])) NOT (“skin and connective tissue diseases”[MeSH Terms])). Biologics included: adalimumab, secukinumab, etanercept, infliximab, ustekinumab, ixekizumab, guselkumab, risankizumab, apremilast, baricitinib, ruxolitinib, brodalumab, dupilumab, and belimumab. Studies describing off-label treatments of patients with rheumatic conditions were included. Data extracted from eligible studies included study design, sample size, biologic dosing and duration, clinical outcomes, and efficacy measures. Studies were then evaluated for their levels of evidence according to the Oxford Centre of Evidence-Based Medicine.

Results: Multiple biologics—including adalimumab, brodalumab, etanercept, infliximab, ixekizumab, risankizumab, ustekinumab, and secukinumab—are indicated for psoriasis. Among these, all except brodalumab are also approved for psoriatic arthritis (PsA), and several are indicated for ankylosing spondylitis (AS). Secukinumab has additional approvals for non-radiographic axial spondyloarthritis and enthesitis-related arthritis, while belimumab is specifically approved for SLE. Adalimumab, etanercept, infliximab, secukinumab are also indicated for rheumatoid arthritis (RA). In a case series of 45 patients, off-label use of TNF inhibitors (infliximab, etanercept, adalimumab) for SAPHO syndrome resulted in 93.3% of patients experiencing musculoskeletal symptom relief and 72.4% showing skin symptom improvement. IL-17/IL-23 inhibitors had moderate efficacy, with ustekinumab improving skin symptoms in 50% of patients and musculoskeletal symptoms in 60%, while secukinumab led to improvements in 57.1% and 37.5%, respectively. In SLE, a randomized controlled trial of ustekinumab showed a 28% greater SRI-4 response compared to placebo. Additionally, in an open-label 28-week trial for AS, off-label ustekinumab use led to reduced symptoms and inflammation by week 24.

Conclusion: This review highlights the expanding role of biologics in the treatment of rheumatologic conditions beyond their primary dermatologic indications. Their interdisciplinary applications present new opportunities for research and clinical practice, underscoring the need for further investigation to optimize their use and broaden their therapeutic scope.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluating-biologic-effectiveness-in-co-occurring-dermatologic-and-rheumatic-disease-a-systematic-review/