Long-term anakinra therapy in Schnitzler syndrome: real-world evidence on remission of neutrophilic dermatitis and systemic inflammation, safety, biomarker insights and dose optimization.

Introduction: Schnitzler syndrome (SchS) is a rare, late-onset, acquired autoinflammatory disorder characterized by recurrent urticarial lesions, monoclonal gammopathy and systemic inflammation. Although interleukin-1 (IL-1) blockade with anakinra is considered as a standard of care, real-world data on long-term outcomes, biomarker utility and dose reduction remain limited. To evaluate the long-term efficacy and safety of anakinra, the utility of inflammatory biomarkers for disease monitoring, the feasibility of dose reduction and diagnostic delay in a cohort of Polish patients with SchS. Methods: We conducted a retrospective observational study of 13 adults with SchS treated with anakinra at two Polish tertiary referral centers between 2018 and 2025. Clinical manifestations, laboratory parameters, treatment response, adverse events and longitudinal follow-up data were analyzed. Receiver operating characteristic (ROC) analyses were used to compare biomarkers of disease activity, including serum amyloid A (SAA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, D-dimers and complete blood count (CBC)-derived inflammatory indices. Results: All 13 patients achieved rapid complete clinical remission within 48 hours of starting anakinra, accompanied by significant reductions in CRP and SAA. Remission was sustained over a median follow-up of 38.2 months (maximum 92.5 months), with no treatment discontinuations. In 3 patients (23%), dosing intervals were successfully extended to every 48-72 hours without loss of disease control. ROC analyses revealed that SAA showed the highest discriminatory power for distinguishing active disease from remission (AUC 0.974), outperforming ESR, fibrinogen and D-dimers. CBC-derived inflammatory indices declined markedly after treatment initiation but served mainly as adjunctive rather than primary monitoring tools. The therapy was well tolerated with no serious adverse events. The most frequent events were injection-site reactions, mild paradoxical psoriasis, transient neutropenia and consistent weight gain. Median diagnostic delay was 49 months. Conclusions: Anakinra provides highly effective and safe long-term disease control in SchS. SAA appears to be the most reliable biomarker for monitoring disease activity, while cautious interval prolongation may be feasible in selected patients in sustained remission. Furthermore, treatment-associated weight gain is a consistent clinical observation requiring attention.