ETD

• Alopecia Areata
• Baricitinib
• Inflammatory Indices
• Lipid profile

Background: Alopecia areata (AA) is an autoimmune, non-scarring hair loss disorder. Baricitinib, a selective JAK1/JAK2 inhibitor, has emerged as the first oral systemic therapy approved for severe AA, targeting cytokine signaling pathways implicated in disease pathogenesis. Its safety, in particular regarding cardiovascular risk and lipid profile changes, remains a topic of interest. Inflammatory indices such as monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), systemic immunoinflammation index (SII), platelet/lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), and pan-immunoinflammation value (PIV), derived from complete blood counts, provide accessible markers of systemic inflammation by reflecting the balance between innate and adaptive immune responses. These indices have been explored across autoimmune and inflammatory diseases as potential indicators of disease activity and treatment response.
Objectives: The first goal (sub-objective 1) is to describe how JAK1/2 inhibition affects lipid profiles over time, including triglycerides, High-Density Lipoprotein (HDL), Low-Density lipoprotein (LDL) and total cholesterol level. Secondly (sub-objective 2), assess a panel of inflammatory indices derived from blood counts (MLR, NLR, PLR, PIV, SIRI, SII, NLR) in the same cohort to determine their relationship to treatment response and disease burden.
Materials and methods: We have set a single-center observational, retrospective study whose subjects were patients with severe AA followed at the Department of Dermatology the University of Pisa, Pisa (Italy). All patients received baricitinib 4 mg, 1 tablet/day. Visits were performed at baseline, 24, and 52 weeks. At each visit, blood tests were performed, including complete blood count with differential and lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides). NLR (neutrophils/lymphocytes), PLR (platelets/lymphocytes), MLR (monocytes/lymphocytes), SII [(neutrophils × platelets)/lymphocytes], SIRI [(neutrophils × monocytes)/lymphocytes], and PIV [(neutrophils × platelets × monocytes)/lymphocytes] were calculated from the complete blood count.
Results: Our study included 37 patients with AA, predominantly female (67.6%), with a mean age of 40 years. A family history of AA was reported in 18.9% of cases, and autoimmune comorbidities were frequent, most notably Hashimoto’s thyroiditis (40.5%) and celiac disease (8.1%). Baseline hypercholesterolemia was present in 40.5% of patients. The mean disease duration was 12.8 years, with a mean duration of the most recent episode of 5.5 months. All patients had received prior systemic therapy, most commonly corticosteroids (100%), followed by cyclosporine (21.6%) and methotrexate (5.4%). Overall, 73% of patients responded to baricitinib, while 27% were classified as non-responders; response kinetics varied, with early, gradual, and late responders represented. Regarding lipid profiles, total cholesterol increased significantly over 52 weeks, while LDL and HDL levels showed mild, non-significant fluctuations. Triglycerides displayed a non-significant downward trend. These changes indicate modest and clinically insignificant metabolic variations during baricitinib therapy. Analysis of inflammatory indices (SII, NLR, PLR, MLR, PIV, and SIRI) revealed that only NLR and PLR changed significantly over time, particularly between weeks 24 and 52. When comparing responders and non-responders, most indices remained similar throughout follow-up, though PLR consistently differed, being higher in responders with a statistically significant between-group difference. Other indices, including SII, NLR, and PIV, showed parallel but non-significant trends, whereas MLR and SIRI remained stable. Overall, PLR emerged as the most sensitive marker of treatment response, while other hematologic indices exhibited variability without clear prognostic significance.
Conclusions: Our findings indicate that baricitinib treatment in patients with alopecia areata was well tolerated, with only minor metabolic and hematologic variations that largely remained within normal ranges. Lipid changes were modest and not clinically relevant. No significant correlation emerged between blood cell-derived inflammatory indices and disease severity or treatment response.