The objective of this narrative review is to synthesize existing evidence on menstrual‐cycle‐associated variation in patient‐reported outcomes (PROs) in reproductive‐aged women with systemic lupus erythematosus (SLE), integrate comparative findings from disease controls and nondisease controls, identify clinical implications, and indicate directions for future studies. A review of the literature was conducted using PubMed, Medline (Clarivate), JISC Library Hub, PsychINFO, and Web of Science. Inclusion criteria included articles referencing women with SLE, PROs, and menstrual cycle phases. Database research conducted yielded 74 articles with 34 meeting inclusion criteria. Key findings from the review include: (1) biologic plausibility for phase‐linked activity: estrogen signaling via type‐I IFN pathways amplifies proinflammatory cytokine production whereas progesterone decreases this effect. Premenstrual decline may remove this protection. Furthermore, gene expression and peripheral immune cell phenotypes vary with phases of menstrual cycle. (2) Pattern of symptom fluctuation: across studies, premenstrual and menstrual phases are associated with increased pain, fatigue, and mood disturbances. Several observational cohorts report significant worsening of visual analog score pain or fatigue and disease activity scores during menses compared with postovulatory phases. Rheumatoid arthritis and fibromyalgia (FM) cohorts suggest similar findings; FM shows the largest increase in widespread pain with changes in menstrual cycle. Female athlete studies corroborate cycle‐related fluctuations in energy, mood, and pain sensitivity. Menstrual cycle phase is a clinically relevant modulator of impairment to quality of life in reproductive‐aged women with SLE. Recognition of cyclical patterns can improve the interpretation of patient‐reported outcome measure score, reduce misclassification of flares, and support personalized management strategies. Integration of menstrual phase data into routine clinical assessment and trial design is warranted.
Objective To evaluate the utility of novel parameters related to immune cell activation, known as white blood cell parameters of inflammation (WBC‐IP), as biomarkers of disease activity in childhood‐onset systemic lupus erythematosus (cSLE) and compare their performance with conventional markers, including erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and procalcitonin (PCT). Methods We conducted a cross‐sectional analysis, including patients with cSLE with active disease (n = 43), remission (n = 31), and healthy controls (n = 112). In a separate longitudinal cohort, patients with active cSLE at baseline were reassessed after four to six weeks and when achieving inactive disease. WBC‐IP was measured in dipotassium EDTA–anticoagulated tubes using the Sysmex XN‐Series analyzer. Associations with SLEDAI‐2K, clinical SLEDAI‐2K, and physician global assessment (PGA) scores were assessed using Spearman's rank correlation. Diagnostic performance for distinguishing active disease from remission was evaluated by the area under the receiver operating characteristic curve (AUC). Results Significant alterations in neutrophil‐ and lymphocyte‐related parameters were observed across disease states. The proportion of immature granulocytes (IG%) correlated most strongly with the SLEDAI‐2K (r s = 0.51), clinical SLEDAI‐2K (r s = 0.50), and PGA (r s = 0.57; all P < 0.0001) and showed comparable associations with ESR, CRP, and PCT. Longitudinal changes in IG%, neutrophil reactivity intensity, and lymphocyte complexity indices paralleled improvements in disease activity. IG% best discriminated active cSLE among WBC‐IP (AUC 0.90, 95% confidence interval [CI] 0.83–0.98; cutoff >0.35, sensitivity 81.4%, specificity 87.1%), whereas ESR demonstrated the highest AUC among conventional markers (AUC 0.92, 95% CI 0.85–0.99). Conclusion Among the WBC‐IP evaluated, IG% showed the strongest association with disease activity and demonstrated diagnostic performance comparable to that of ESR, suggesting it may represent a potential biomarker of disease activity. Further validation in independent cohorts is warranted. image
Objective Complement activation, particularly through the C5a–C5a receptor axis, plays a pivotal role in the pathogenesis of antineutrophil cytoplasmic antibody–associated vasculitis (AAV) and may represent an important therapeutic target. Avacopan, an oral C5a receptor antagonist, was the first therapy targeting this pathway to enter in clinical practice. Prospective real‐world data on its long‐term effectiveness, safety, and impact on quality of life (QoL) remain limited. In the context of an evolving therapeutic and regulatory landscape, such data provide valuable evidence on the clinical effects of C5a receptor inhibition and may inform the development and evaluation of future complement‐targeted therapies. The objective of this study was to evaluate the real‐world effectiveness, safety, kidney outcomes, and patient‐reported outcomes of avacopan in an Italian cohort of patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Methods This prospective, multicenter, observational study included patients with newly diagnosed or relapsing GPA or MPA who were started on avacopan therapy across 18 Italian centers. Avacopan was administered in combination with standard immunosuppressive therapy, with or without glucocorticoids (GCs). Clinical remission (Birmingham Vasculitis Activity Score = 0), GC‐free remission, kidney parameters, laboratory outcomes, adverse events, and patient‐reported outcomes assessed by the AAV Patient‐Reported Outcome questionnaire were evaluated up to 52 weeks and beyond. Estimated glomerular filtration rate (eGFR) was calculated using the European Kidney Function Consortium equation. Results Forty‐six patients were included (63% women; mean age of 59 years); 61% had relapsing disease, and 70% had kidney involvement at baseline. Clinical remission was achieved by 78%, 88%, and 97% of patients at weeks 12, 26, and 52, respectively. GC‐free remission occurred in 20% at week 12 and 55% at week 52. Mean GC dose decreased from 23 mg/day at baseline to 5 mg/day by week 12 ( P < 0.001). Kidney function improved over time, with median eGFR increasing from 30.5 mL/min/1.73 m 2 at baseline to 53.5 mL/min/1.73 m 2 at week 52 ( P = 0.002). Significant improvements in QoL were observed as early as week 12 and were sustained until week 52, particularly in the physical function domain. Adverse events were mild to moderate; infections were the most frequent events (40%). Disease relapses were uncommon and occurred exclusively in patients treated for relapsing disease. Conclusion In this real‐world Italian cohort, patients treated with avacopan achieved high remission rates, substantial GC reduction, improvement in kidney function, and sustained QoL benefits. These findings provide prospective real‐world evidence on the clinical outcomes associated with C5a receptor inhibition in routine clinical practice while acknowledging the observational design of the study.
