Since the 1990s—especially after the 2015 US Precision Medicine Initiative—precision medicine focused on stratifying patients by molecular profiles to match them with targeted therapies. This is particularly relevant to heterogeneous autoimmune diseases such as PsA, SLE, RA, IgG4-RD, and ANCA-associated vasculitis, where “one-size-fits-all” treatment is often inefficient. Peripheral immune cell phenotyping has emerged as a practical way to stratify patients when biopsies are hard to obtain, defining immunologic subgroups and linking them to disease activity and treatment response. Supported by mass cytometry and multi-omics, these approaches are starting to map the cellular and molecular heterogeneity driving autoimmune disease.

Psoriatic arthritis illustrates how this can work in practice. In a real-world study, patients were grouped into Th17-dominant, Th1-dominant, mixed Th1/Th17-high, or Th1/Th17-low patterns and then treated with ustekinumab, IL-17 inhibitors, or TNF inhibitors according to their T-helper phenotype. This “strategic bDMARD” approach produced more patients with low disease activity than standard TNF-first treatment, suggesting phenotype-guided therapy can improve outcomes. However, correlations with clinical severity were modest, the methods are complex, and newer agents and additional cell subsets still need to be incorporated. Combining peripheral phenotyping with tissue or liquid biopsies, serum cytokines, and longitudinal single-cell multi-omics may ultimately enable mature precision medicine in PsA and other autoimmune diseases.

Reference: Miyagawa I, Tanaka Y. Dawn of Precision Medicine in Psoriatic Arthritis. Front Med (Lausanne). 2022 Mar 18;9:851892. doi: 10.3389/fmed.2022.851892. PMID: 35372404; PMCID: PMC8973395.

Researchers conducted a single-center, retrospective study to compare two common post–biologic-failure strategies in psoriatic arthritis (PsA): cycling TNF inhibitors (TNFi→TNFi) versus swapping mechanism of action between TNFi and IL-17 inhibitors (TNFi→IL-17i or IL-17i→TNFi). They analyzed 122 adults with PsA (CASPAR criteria) treated between 2016–2022 and grouped them as cycling (CG), TNFi→IL-17i (SG1), or IL-17i→TNFi (SG2). One-year drug retention was 67% in CG, 71.8% in SG1, and 45.5% in SG2. At two years, persistence remained numerically higher in SG1 (58%) than in CG (51%) or SG2 (34%), although these differences did not reach overall statistical significance. Lack or loss of efficacy was the main reason for discontinuation across strategies.

Cox regression suggested that swapping from TNFi to IL-17i (SG1) and older age were associated with longer treatment persistence, while higher baseline DAPSA and later calendar year of switch predicted shorter retention. These findings support the idea that changing mechanism of action after TNFi failure may offer some advantage over TNFi cycling, particularly in second or third biologic lines. The findings are also consistent with registry data showing diminished effectiveness of subsequent TNFi use. However, the authors note substantial limitations, including retrospective single-center design, small IL-17i→TNFi group, potential selection bias, and lack of detailed data on factors such as obesity, smoking, and PsA phenotype. They conclude that TNFi→IL-17i switching may be preferable to TNFi cycling in real-world practice, but larger, prospective, multicenter studies are needed to confirm this strategy.

Reference: Lumetti F, Ariani A, Marchesoni A, et al. Cycling versus swapping strategies with TNF-α inhibitors and IL-17 inhibitors in psoriatic arthritis in clinical practice. Sci Rep. 2024 Oct 22;14(1):24922. doi: 10.1038/s41598-024-75190-x. PMID: 39438513; PMCID: PMC11496729.

Researchers conducted a retrospective study of 78 patients with mild psoriasis (PsO) who had no musculoskeletal (MSK) symptoms and were not receiving systemic therapy, to identify factors associated with later development of psoriatic arthritis (PsA). Patients were followed by dermatologists and evaluated by rheumatologists with clinical assessment and musculoskeletal ultrasound (US) at baseline and during follow-up. At baseline, many patients were overweight or obese (48.7%), nearly 40% had nail disease, and US frequently showed structural or inflammatory changes such as calcifications (56.4%), bursitis at entheses (30.4%), and low-grade Power Doppler signal (11.5%).

Among the 60 patients who completed follow-up (median ~6.4 years), over half (56.6%) developed MSK symptoms, and a small subset progressed to inflammatory disease: 8.3% developed inflammatory MSK symptoms and 5.5% met CASPAR criteria for PsA, with a mean time to PsA diagnosis of about 20 months. Higher baseline BMI, larger abdominal circumference, and elevated pain and fatigue scores were significantly associated with later MSK symptom development, as were higher baseline US total scores. Notably, US-detected bursitis was present in 80% of patients who developed inflammatory symptoms. The investigators concluded that, in systemic therapy–naïve patients with mild PsO, ultrasound-detected bursitis and higher baseline BMI, pain, and fatigue may help identify individuals at increased risk of progressing to PsA.

Reference: For Physician's Weekly. Key Ultrasound Markers Predict Psoriatic Arthritis. Physician's Weekly. Published June 15, 2025. Accessed December 8, 2025. https://www.physiciansweekly.com/post/key-ultrasound-markers-predict-psoriatic-arthritis